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Larsen ML, Nørgaard L, Linge P, Larsen JB, Langkilde HZ, Hauge EM, Thiel S, Voss A, Bengtsson A, Troldborg A. Molecular mechanisms underlying thrombosis in systemic lupus erythematosus - A Systematic review. Semin Arthritis Rheum 2025; 72:152707. [PMID: 40086157 DOI: 10.1016/j.semarthrit.2025.152707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 02/13/2025] [Accepted: 02/27/2025] [Indexed: 03/16/2025]
Abstract
Patients with systemic lupus erythematosus (SLE) face an approximately 30 % risk of thrombosis post-diagnosis. However, there remains significant knowledge gaps regarding causative mechanisms, and there is a lack of specific antithrombotic guidelines. This systematic review aims to examine the existing literature regarding the mechanisms contributing to thrombosis risk in SLE, focusing on five predefined procoagulant domains: autoantibodies (including antiphospholipid antibodies (aPL)), the complement system, platelets, the endothelium, and the coagulation system. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statements and searched in PubMed and Embase without time restrictions. Risk of bias assessment was performed using a pre-specified evaluation tool. Out of 3,747 initially identified publications, 30 studies were included, with 28 demonstrating robust methodological quality in the risk of bias assessment. The studies were experimental, involving blood samples from cross-sectional SLE cohorts, except one animal -and one case-control study. We identified six different thrombosis mechanisms of action. Most studies concentrated on autoantibodies, predominantly aPL. Shared mechanisms between aPL and other autoantibodies may account for the increased thrombosis risk in aPL-negative SLE patients. Significant knowledge gaps remain, particularly regarding the role of the complement system in SLE-related thrombosis. Also, most research relies on cross-sectional designs, emphasizing the need for prospective cohort studies to better assess clinical factors. Finally, comprehensive studies examining the interactions between multiple procoagulant factors and their link to thrombosis are lacking. Closing these gaps in future research could improve both preventive and personalized treatment strategies for thrombosis in SLE.
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Affiliation(s)
- Mads L Larsen
- Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
| | - Laura Nørgaard
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Petrus Linge
- Department of Clinical Sciences, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Julie B Larsen
- Department of Clinical Biochemistry, Regional Hospital Horsens, Horsens, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Henrik Z Langkilde
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Rheumatology, Odense University Hospital, Odense, Denmark
| | - Ellen M Hauge
- Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Steffen Thiel
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Anne Voss
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Rheumatology, Odense University Hospital, Odense, Denmark
| | - Anders Bengtsson
- Department of Clinical Sciences, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Anne Troldborg
- Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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von Känel R. Stress-Induced Hypercoagulability: Insights from Epidemiological and Mechanistic Studies, and Clinical Integration. Semin Thromb Hemost 2025; 51:381-400. [PMID: 38914118 DOI: 10.1055/s-0044-1787660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced hypercoagulability in clinical medicine. In particular, the findings from numerous prospective cohort studies indicate that stress and hemostatic factors of a hypercoagulable state are associated with increased incident risk and poor prognosis for atherosclerotic cardiovascular disease and venous thromboembolism. Mendelian randomization studies suggest that these associations are partially causal. The review synthesizes extensive research on the link between acute and chronic stress and hypercoagulability, outlining a potential pathway from stress to thrombosis risk. Consistent with the allostatic load concept, acute stress-induced hypercoagulability, initially adaptive, can turn maladaptive under chronic stress or excessive acute stress, leading to arterial or venous thrombotic events. Individuals with predisposing factors, including atherosclerosis, thrombophilia, or immobilization, may exhibit an increased risk of thrombotic disease during stress. Contextual sociodemographic characteristics, the stress experience, and coping resources additionally modulate the extent of stress-induced hypercoagulability. Research into the neuroendocrine, cellular, and molecular bases reveals how stress influences platelet activation coagulation and fibrinolysis. The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, along with vagal withdrawal, and the effects of catecholamines, cortisol, and vasopressin, are the central mechanisms involved. Hemoconcentration, inflammation, endothelial dysfunction, and thrombopoiesis additionally contribute to stress-induced hypercoagulability. Further research is needed to prove a causal link between chronic stress and hypercoagulability. This includes exploring its implications for the prevention and management of thrombotic diseases in stressed individuals, with a focus on developing effective psychosocial and pharmacological interventions.
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Affiliation(s)
- Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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3
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Sunthankar SD, Hill KD, Jacobs JP, Baldwin HS, Jacobs ML, Li JS, Graham EM, Blasiole B, Husain SA, Bleiweis MS, Mettler B, Benscoter A, Wald E, Karamlou T, Van Bergen AH, Eghtesady P, Scott JP, Anderson BR, Alfieris G, Vener DF, Kannankeril PJ. Methylprednisolone for Infant Heart Surgery: Subpopulation Analyses of a Randomized Controlled Trial. Crit Care Med 2025:00003246-990000000-00527. [PMID: 40396812 DOI: 10.1097/ccm.0000000000006721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
OBJECTIVES Evaluate benefits and harms of prophylactic intraoperative methylprednisolone in subpopulations undergoing infant heart surgery. DESIGN Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial, a double-blind randomized placebo-controlled trial. SETTING Twenty-four congenital heart centers. PATIENTS Infants (< 1 yr old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) mortality category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD). INTERVENTIONS Methylprednisolone (30 mg/kg) vs. placebo administered into cardiopulmonary bypass pump-priming fluid. MEASUREMENTS AND MAIN RESULTS Six postoperative outcomes: steroid use, acute kidney injury (AKI), thrombosis, infections, prolonged mechanical ventilation, peak blood glucose levels, and insulin exposure. One thousand two hundred patients received methylprednisolone or placebo. Beneficial effects associated with methylprednisolone included reduced use of postoperative hydrocortisone in neonates (odds ratio [OR], 0.39 [0.25-0.60]), both STAT category groups (1-3: OR, 0.64 [0.46-0.89]; 4-5: OR, 0.57 [0.34-0.97]), term infants (OR, 0.63 [0.47-0.83]), and those without CSD (OR, 0.63 [0.46-0.86]). Methylprednisolone was associated with lower thrombosis occurrence among neonates (OR, 0.37 [0.16-0.87]) and term infants (OR, 0.38 [0.19-0.75]). Adverse associations included increased thrombosis among premature infants (p = 0.005), increased AKI among neonates (OR, 1.55 [1.02-2.37]) and those following STAT category 1-3 operations (OR, 1.34 [1.02-1.75]), and increased peak blood glucose levels and insulin exposure (all subgroups; p < 0.001). No increase in overall infection or reduction in prolonged mechanical ventilation with methylprednisolone. CONCLUSIONS Both beneficial and adverse associations were observed with prophylactic methylprednisolone. Reduction in postoperative hydrocortisone administration and absence of increased infection rates are arguments favoring prophylactic methylprednisolone use. Methylprednisolone was associated with increased peak blood glucose levels and a neutral to harmful association with odds of AKI. These data suggest certain subpopulations may benefit from prophylactic intraoperative methylprednisolone without significant harm.
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Affiliation(s)
- Sudeep D Sunthankar
- Thomas P. Graham Jr. Division of Pediatric Cardiology and Center for Pediatric Precision Medicine, Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt and Vanderbilt University Medical Center, Nashville, TN
| | - Kevin D Hill
- Division of Pediatric Cardiology, Duke University Medical Center, Durham, NC
| | - Jeffrey P Jacobs
- Division of Cardiac Surgery, University of Florida, Gainesville, FL
| | - H Scott Baldwin
- Thomas P. Graham Jr. Division of Pediatric Cardiology and Center for Pediatric Precision Medicine, Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt and Vanderbilt University Medical Center, Nashville, TN
| | - Marshall L Jacobs
- Division of Cardiac Surgery, Johns Hopkins School of Medicine, Baltimore, MD
| | - Jennifer S Li
- Division of Pediatric Cardiology, Duke University Medical Center, Durham, NC
| | - Eric M Graham
- Division of Pediatric Cardiology, Medical University of South Carolina, Charleston, SC
| | - Brian Blasiole
- Division of Pediatric Cardiac Anesthesiology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - S Adil Husain
- Division of Cardiac Surgery, Primary Children's Hospital, Salt Lake City, UT
| | - Mark S Bleiweis
- Division of Cardiac Surgery, University of Florida, Gainesville, FL
| | - Bret Mettler
- Division of Cardiac Surgery, Johns Hopkins School of Medicine, Baltimore, MD
| | - Alexis Benscoter
- Division of Pediatric Cardiology, Cincinnati Children's Hospital, Cincinnati, OH
| | - Eric Wald
- Division of Pediatric Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Tara Karamlou
- Division of Cardiac Surgery, Cleveland Clinic, Cleveland, OH
| | | | - Pirooz Eghtesady
- Division of Cardiac Surgery, Washington University School of Medicine, St. Louis, MO
| | - John P Scott
- Division of Pediatric Cardiology, Medical College of Wisconsin, Madison, WI
| | - Brett R Anderson
- Division of Pediatric Cardiology, Icahn School of Medicine at Mt Sinai, New York, NY
| | - George Alfieris
- Division of Cardiac Surgery, University of Rochester, Rochester, NY
| | - David F Vener
- Division of Pediatric Cardiac Anesthesiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX
| | - Prince J Kannankeril
- Thomas P. Graham Jr. Division of Pediatric Cardiology and Center for Pediatric Precision Medicine, Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt and Vanderbilt University Medical Center, Nashville, TN
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Mori Y, Tarasawa K, Tanaka H, Kamimura M, Harada K, Mori N, Fushimi K, Aizawa T, Fujimori K. Thromboembolic and infectious complication risks in TKA and UKA: evidence from a Japanese nationwide cohort. Knee Surg Relat Res 2025; 37:19. [PMID: 40341061 PMCID: PMC12063263 DOI: 10.1186/s43019-025-00273-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 04/23/2025] [Indexed: 05/10/2025] Open
Abstract
INTRODUCTION Total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) are widely used to treat knee osteoarthritis. TKA significantly contributes to long-term pain relief and joint function improvement, while UKA offers faster recovery and reduced early complications. However, TKA and UKA complication risks, aside from conditions such as deep vein thrombosis, have not been thoroughly investigated. This study compares the in-hospital complication risks of TKA and UKA using a nationwide Japanese database. METHODS A retrospective cohort study was conducted using data from the Japanese Diagnosis Procedure Combination (DPC) database, spanning from April 2016 to March 2023. A total of 259,319 knee arthroplasty cases (TKA: 228,595; UKA: 30,724) were analyzed. Propensity score matching (1:1) was used to adjust for age, sex, comorbidities, and surgical factors, resulting in 30,591 matched pairs. Multivariable logistic regression analyses assessed the risks of complications, including deep vein thrombosis, pulmonary embolism, and surgical site infections. RESULTS Deep vein thrombosis is frequently observed as a complication with a high incidence rate. Even after propensity score matching, the incidence remained significantly higher in the TKA group (8.8%) compared with the UKA group (6.1%) (p < 0.0001). TKA was associated with significantly higher risks of deep vein thrombosis (odds ratio (OR): 1.467, 95% confidence interval (CI) 1.380-1.560, p < 0.0001), pulmonary embolism (OR: 1.709, 95% CI 1.182-2.470, p = 0.0044), and surgical site infection (OR: 1.512, 95% CI 1.277-1.790, p < 0.0001) compared with UKA. UKA showed lower risks of cognitive dysfunction, pneumonia, transfusion requirements, and shorter hospital stays. However, patients who underwent UKA had a higher risk of periprosthetic fractures. CONCLUSIONS This study highlights the distinct risk profiles of TKA and UKA, emphasizing the need for tailored surgical decision-making. UKA offers advantages in reducing complications for specific patient populations. Strengthening prophylactic measures is crucial for effectively managing thromboembolic and infectious complications in patients undergoing TKA.
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Affiliation(s)
- Yu Mori
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan.
| | - Kunio Tarasawa
- Department of Health Administration and Policy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Hidetatsu Tanaka
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Masayuki Kamimura
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Kento Harada
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Naoko Mori
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan
| | - Toshimi Aizawa
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Kenji Fujimori
- Department of Health Administration and Policy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
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Dougherty JM, Gerhardinger LJ, Johnson PL, Regenbogen SE, Scott JW, Sangji NF, Jean RA, Hemmila MR, Oliphant BW. Venous thromboembolism events in trauma patients after hospital discharge. J Trauma Acute Care Surg 2025; 98:704-712. [PMID: 39956985 DOI: 10.1097/ta.0000000000004527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2025]
Abstract
BACKGROUND Venous thromboembolism (VTE) is common after major injury. This elevated VTE risk likely continues beyond hospital discharge, but a lack of postdischarge surveillance limits our understanding of this complication and opportunities for improving outcomes. We aimed to characterize the incidence and risk factors of trauma patients who developed a VTE in the first year after discharge from their index hospital admission. METHODS We used data from adult inpatients (18 years or older) from 35 American College of Surgeons - Committee on Trauma-verified Level 1 and Level 2 trauma centers in a statewide trauma quality improvement program from 2018 to 2023. The incidence and timing of a postdischarge VTE were identified from linked longitudinal insurance claims data, and multivariable logistic regression was performed to identify predictors of a postdischarge event. RESULTS Of 34,421 trauma registry and claims matched patients identified, 1,487 (4.3%) developed a VTE within the first year after discharge from the trauma center, compared with 280 VTE events (0.8%) diagnosed during the index admission. The incidence of VTE remained elevated well after discharge, with 40% occurring in the first 30 days and 73% within the first 3 months. Multiple patient, injury, and treatment factors were associated with postdischarge VTE risk, including having an operation, a significant spine injury, Black race, and receiving a blood transfusion. CONCLUSION The risk of VTE extends well beyond the index hospitalization for trauma patients, as the majority of events occur after discharge. Understanding and improving VTE outcomes in trauma patients will require a longitudinal patient record that captures these complications. Postdischarge VTEs are an underrecognized trauma-related morbidity but are also very treatable through a better understanding of the risk factors and the optimal prophylactic strategy. LEVEL OF EVIDENCE Prognostic and Epidemiologic; Level IV.
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Affiliation(s)
- Jacob M Dougherty
- From the Wayne State University School of Medicine (J.M.D.), Detroit; Department of Surgery (L.J.G., P.L.J., S.E.R., N.F.S., R.A.J., M.R.H.) and Center for Healthcare Outcomes and Policy (L.J.G., P.L.J., S.E.R., N.F.S., R.A.J., M.R.H., B.W.O.), University of Michigan, Ann Arbor, Michigan; Department of Surgery (J.W.S.), University of Washington, Seattle, Washington; and Department of Orthopaedic Surgery (B.W.O.), University of Michigan, Ann Arbor, Michigan
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Marín-Jiménez I, Carpio D, Hernández V, Muñoz F, Zatarain-Nicolás E, Zabana Y, Mañosa M, Rodríguez-Moranta F, Barreiro-de Acosta M, Gutiérrez Casbas A. Spanish Working Group in Crohn's Disease and Ulcerative Colitis (GETECCU) position paper on cardiovascular disease in patients with inflammatory bowel disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502314. [PMID: 39615874 DOI: 10.1016/j.gastrohep.2024.502314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/24/2024] [Indexed: 01/12/2025]
Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Therefore, it is essential to understand their relationship and prevalence in different diseases that may present specific risk factors for them. The objective of this document is to analyze the specific prevalence of CVD in patients with inflammatory bowel disease (IBD), describing the presence of classical and non-classical cardiovascular risk factors in these patients. Additionally, we will detail the pathophysiology of atherosclerosis in this patient group and the different methods used to assess cardiovascular risk, including the use of risk calculators in clinical practice and different ways to assess subclinical atherosclerosis and endothelial dysfunction. Furthermore, we will describe the potential influence of medication used for managing patients with IBD on cardiovascular risk, as well as the potential influence of commonly used drugs for managing CVD on the course of IBD. The document provides comments and evidence-based recommendations based on available evidence and expert opinion. An interdisciplinary group of gastroenterologists specialized in IBD management, along with a consulting cardiologist for this type of patients, participated in the development of these recommendations by the Spanish Group of Work on Crohn's Disease and Ulcerative Colitis (GETECCU).
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Affiliation(s)
- Ignacio Marín-Jiménez
- Sección de Gastroenterología, Servicio de Aparato Digestivo, Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España.
| | - Daniel Carpio
- Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, España; Grupo de Investigación en Hepatología-Enfermedades Inflamatorias Intestinales, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Pontevedra, España
| | - Vicent Hernández
- Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, Pontevedra, España; Grupo de Investigación en Patología Digestiva, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Pontevedra, España
| | - Fernando Muñoz
- Servicio de Digestivo. Complejo Asistencial Universitario de Salamanca, Salamanca, España
| | - Eduardo Zatarain-Nicolás
- Servicio de Cardiología, Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid; CIBERCV, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Universidad Complutense de Madrid, Madrid, España
| | - Yamile Zabana
- Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Terrasa, Barcelona, España
| | - Míriam Mañosa
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España
| | - Francisco Rodríguez-Moranta
- Servicio de Aparato Digestivo, Hospital Universitario de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
| | - Manuel Barreiro-de Acosta
- Servicio de Gastroenterología, Hospital Clínico Universitario de Santiago, A Coruña, España; Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña, España
| | - Ana Gutiérrez Casbas
- Servicio Medicina Digestiva, Hospital General Universitario Dr Balmis de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), CIBERehd, Alicante, España
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Mamizu H, Tsuji J, Kumagai M, Kuwana C, Miyagatani M, Mamizu M, Ishikawa D, Kawakami H, Furukawa T, Ishida T, Kaneko C, Sakai T. An autopsy for persistent coronavirus disease 2019 pneumonia during follicular lymphoma treatment: A case report. Intern Med 2025:5283-25. [PMID: 40254437 DOI: 10.2169/internalmedicine.5283-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/22/2025] Open
Abstract
A 66-year-old man who was receiving treatment for B-cell non-Hodgkin lymphoma presented with fever. He tested positive for severe acute respiratory syndrome coronavirus 2 antigen. Chest computed tomography (CT) revealed pneumonia. Therefore, remdesivir was administered to the patient. However, steroid pulse therapy was initiated owing to the lack of any symptom improvement and a worsening of the CT findings. The patient developed recurrent fever following a reduction in the steroid dose. His respiratory condition gradually worsened, and he eventually died. Autopsy revealed diffuse alveolar damage. In high-risk patients with hematologic malignancy, COVID-19 vaccination should be repeated at shorter intervals to avoid increasing the viral load during the COVID-19 infection.
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Affiliation(s)
- Hikaru Mamizu
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Jun Tsuji
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Morihiro Kumagai
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Chika Kuwana
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Masanori Miyagatani
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Maiko Mamizu
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Daisuke Ishikawa
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Hidenori Kawakami
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Toshiki Furukawa
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Takashi Ishida
- Department of Internal Medicine, Niigata Prefectural Central Hospital, Japan
| | - Chizuru Kaneko
- Department of Diagnostic Pathology, Niigata Prefectural Central Hospital, Japan
| | - Takeshi Sakai
- Department of Diagnostic Pathology, Niigata Prefectural Central Hospital, Japan
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Scimeca G, Krishnathasan D, Rashedi S, Lan Z, Sato A, Hamade N, Bejjani A, Khairani CD, Davies J, Porio N, Assi AA, Armero A, Tristani A, Ortiz-Rios MD, Nauffal V, Almarzooq Z, Wei E, Zuluaga-Sánchez V, Zarghami M, Achanta A, Jesudasen SJ, Tiu B, Merli GJ, Leiva O, Fanikos J, Sharma A, Rizzo S, Pfeferman MB, Morrison RB, Vishnevsky A, Hsia J, Nehler MR, Welker J, Bonaca MP, Carroll B, Goldhaber SZ, Campia U, Bikdeli B, Piazza G. Predictors of venous thromboembolic events in hospitalized patients with COVID-19. J Thromb Thrombolysis 2025; 58:485-496. [PMID: 40064840 DOI: 10.1007/s11239-025-03078-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/13/2025] [Indexed: 05/02/2025]
Abstract
COVID-19 is associated with an increased risk of venous thromboembolism (VTE) in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We utilized data from hospitalized patients in the CORONA-VTE Network, a United States multicenter registry of adult patients with PCR-confirmed COVID-19 (N = 3,844). The primary outcome was time-to-first event for a composite of adjudicated pulmonary embolism or deep vein thrombosis during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. We conducted cause-specific Cox regression analysis adjusted for the selected variables for each imputed dataset and pooled the estimated HRs for reporting (p < 0.05 for significance). VTE occurred in 206 patients, with a cumulative incidence of 5.3% at 90 days. The covariates associated with increased risk of VTE were history of VTE (HR: 1.71; 95% CI: 1.11-2.63), corticosteroid therapy (HR: 1.76; 95% CI: 1.32-2.33) and known thrombophilia (HR: 3.56; 95% CI: 1.54-8.21) while therapeutic anticoagulation at baseline (HR: 0.42; 95% CI: 0.26-0.69), antecedent use of statins (HR: 0.67; 95% CI: 0.50-0.90), and prophylactic anticoagulation during hospitalization (HR: 0.52; 95% CI: 0.38-0.71) were associated with reduced risk of VTE. While prior VTE, corticosteroid therapy, and known thrombophilia were associated with an increased risk of VTE, prescriptions of prophylactic and therapeutic anticoagulation, and statins were associated with a decreased risk. Once externally validated, these findings may inform risk assessment in hospitalized patients with COVID-19.
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Affiliation(s)
- Giovanni Scimeca
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Mount Auburn Hospital, Harvard Medical School, Boston, MA, USA
| | - Darsiya Krishnathasan
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Sina Rashedi
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Zhou Lan
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Center for Clinical Investigation, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Alyssa Sato
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Nada Hamade
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Antoine Bejjani
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Candrika D Khairani
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Julia Davies
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Nicole Porio
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Ali A Assi
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Andre Armero
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Anthony Tristani
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Marcos D Ortiz-Rios
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Victor Nauffal
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Zaid Almarzooq
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Eric Wei
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Valeria Zuluaga-Sánchez
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mehrdad Zarghami
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Aditya Achanta
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Sirus J Jesudasen
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Bruce Tiu
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Geno J Merli
- Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Orly Leiva
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - John Fanikos
- Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Aditya Sharma
- Department of Medicine, Cardiovascular Medicine, University of Virginia Health, Charlottesville, VA, USA
| | - Samantha Rizzo
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mariana B Pfeferman
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ruth B Morrison
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Alec Vishnevsky
- Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Judith Hsia
- CPC Clinical Research, Aurora, CO, USA
- Department of Medicine, University of Colorado, Aurora, CO, USA
| | | | - James Welker
- Anne Arundel Research Institute, Annapolis, MD, USA
| | - Marc P Bonaca
- CPC Clinical Research, Aurora, CO, USA
- Department of Medicine, University of Colorado, Aurora, CO, USA
| | - Brett Carroll
- Smith Center for Cardiovascular Outcomes Research, Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Samuel Z Goldhaber
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Umberto Campia
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Behnood Bikdeli
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
- YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, CT, USA
| | - Gregory Piazza
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
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9
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Razo-Blanco-Hernández DM, Hernández-Mariano JÁ, Díaz-Cureño MA, Navarrete-Martínez L, Bravata-Alcántara JC, Rivera-Sanchez R, Fernandez-Sánchez V. Association between SARS-CoV-2 viral load and serum biomarkers with mortality in Mexican patients. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2025; 14:133. [PMID: 40271273 PMCID: PMC12017452 DOI: 10.4103/jehp.jehp_1481_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/05/2024] [Indexed: 04/25/2025]
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has resulted in high mortality among hospitalized patients; thus, identifying mortality markers in treating these patients is essential. To evaluate the association between viral load and serum biomarkers with mortality among hospitalized patients with COVID-19. MATERIALS AND METHODS A retrospective cohort study was conducted among 198 inpatient records from a tertiary hospital in Mexico City between January and April 2021. The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and serum biomarkers with death due to COVID-19 was assessed using Cox regression models. RESULTS The median age was 54.9 years, and 61.6% were males. The mortality rate was 43.4%. After adjusting for potential confounders, patients with higher viral load [adjusted hazard ratio (aHR) = 1.56; 95% confidence interval (95% CI) = 1.01, 2.42; P value = 0.041]; and higher concentrations of BUN (aHR = 4.87;95% CI = 2.70, 8.79; P value = 0.001), creatinine (aHR = 1.60;95% CI = 1.01, 2.54; P value = 0.043), osmolality (aHR = 4.37;95% CI = 2.34, 8.14; P value = 0.001), and glucose (aHR = 2.41;95% CI = 1.40, 4.18; P value = 0.001) were more likely to have a fatal prognosis. Conversely, mortality risk was lower among patients with high concentrations of lymphocytes (aHR = 0.47;95% CI = 0.30, 0.72; P value = 0.001). CONCLUSION SARS-CoV-2 viral load and serum biomarkers such as BUN, creatinine, glucose, osmolarity, and lymphocytes could help physicians identify individuals who require closer monitoring.
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Affiliation(s)
| | | | - Mónica A. Díaz-Cureño
- Department of Medical Research and Teaching, Hospital Juárez de México, CDMX, Mexico
| | | | | | | | - Verónica Fernandez-Sánchez
- Department of Research, Hospital Juárez de México, CDMX, Mexico
- Faculty of Superior Studies Iztacala, UNAM, State of Mexico, Mexico
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10
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Han B. [Limitations and challenges of glucocorticoids in the treatment of paroxysmal nocturnal hemoglobinuria]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2025; 46:193-197. [PMID: 40355348 PMCID: PMC12038475 DOI: 10.3760/cma.j.cn121090-20241213-00568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Indexed: 05/14/2025]
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that mainly occurs in young adults and is characterized by bone marrow failure, persistent intravascular hemolysis and thrombosis, all of which can cause severe end-organ damage, increase the risk of early death, and cause a severe disease burden in patients. In China, based on the historic reasons, glucocorticoids are still routinely used in many places. However, the effects of glucocorticoids on PNH hemolysis are uncertain. Evidence-based medical data and clinical benefits for glucocorticoid on PNH are missing, but the long-term use of glucocorticoids significantly increases the risk of adverse reactions in patients. Since PNH needs a lifelong follow-up and management, long-term glucocorticoid therapy will unavoidably seriously damage the health of patients. Therefore, glucocorticoids are not recommended for the treatment of PNH, either from domestic or overseas guidelines, or expert consensus. In this article, the limitations and challenges of glucocorticoids in the treatment of PNH were expounded upon, in order to encourage more effective and safe strategies to be accepted in China.
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Affiliation(s)
- B Han
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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11
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Fang YJ, Hsieh HH, Lin HJ, Lin CL, Lee WY, Chen CH, Tsai FJ, You BJ, Tien N, Lim YP. Relationship between venous thromboembolism and inflammatory bowel disease in Taiwan: a nationwide retrospective cohort study. BMC Cardiovasc Disord 2025; 25:153. [PMID: 40050756 PMCID: PMC11884027 DOI: 10.1186/s12872-025-04600-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 02/21/2025] [Indexed: 03/10/2025] Open
Abstract
BACKGROUND Inflammation significantly influences thrombosis development, with venous thromboembolism (VTE) risk linked to various systemic inflammatory diseases, but not fully established in inflammatory bowel disease (IBD). Using a population-based cohort study conducted in Taiwan, we investigated the impact of IBD on the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE), as well as the impact of anti-IBD treatments. METHODS A study was conducted on a cohort of patients with IBD diagnosed between 2010 and 2019 using the National Health Insurance database. The risks of VTE, DVT, and PE, as well as anti-IBD treatment use, were examined using Cox proportional hazard regression analysis. RESULTS The overall number of person-years recorded for 12,126 patients with IBD (mean age: 49.18 years; 55.31% male) and 12,126 controls (mean age: 49.19 years; 55.31% male) was 64,057 and 72,056, with a follow-up duration for the two cohorts was 5.28 and 5.94 years, respectively. After adjusting for age, gender, and comorbidities, the adjusted hazard ratios (aHRs) of VTE, DVT, and PE in patients with IBD were 5.58 [95% confidence interval (CI) = 3.97-7.87], 5.48 (95% CI = 3.83-7.86), and 4.96 (95% CI = 2.00-12.35) times higher, respectively, than those in the control cohort. Male patients with IBD and those under the age of 50 were more likely to develop VTE (aHR = 8.54, 95% CI = 2.00-12.35; aHR = 15.75, 95% CI = 5.73-43.26, respectively). Compared to the cohort of patients with IBD receiving no treatment, patients receiving anti-IBD treatments did not show a significant change in the risk of developing VTE. Additionally, compared to the IV steroid cohort, patients with IBD who only used oral steroids had a substantially lower incidence of VTE, particularly with average doses of ≤ 80 mg (aHR = 0.24, 95% CI = 0.10-0.59). CONCLUSION Patients with IBD are at an increased risk of developing VTE, particularly DVT and PE. While our study found that anti-IBD treatments did not significantly alter this risk, proactive management of associated factors and close monitoring remains essential for preventing VTE in this population. Identifying and addressing specific associated factors should be prioritized in clinical practice to mitigate the heightened risk of VTE in IBD patients.
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Affiliation(s)
- Yi-Jen Fang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung, Taiwan
- Digestive Disease Center, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Hui-Hsia Hsieh
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 66, Sec. 1, Fengxing Rd., Tanzi Dist, Taichung, 427213, Taiwan.
- Department of Pharmacy, College of Pharmacy, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan.
| | - Heng-Jun Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Wan-Yi Lee
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 66, Sec. 1, Fengxing Rd., Tanzi Dist, Taichung, 427213, Taiwan
- Department of Pharmacy, College of Pharmacy, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan
| | - Chi-Hua Chen
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 66, Sec. 1, Fengxing Rd., Tanzi Dist, Taichung, 427213, Taiwan
| | - Fuu-Jen Tsai
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan
- Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan
| | - Bang-Jau You
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan
| | - Ni Tien
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
| | - Yun-Ping Lim
- Department of Pharmacy, College of Pharmacy, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan.
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
- Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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12
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Hu S, Gu Y, Zhao T, Zhang K, Li J, Zhou C, Song H, Liu Z, Ji X, Duan J. Steroids combined with anticoagulant in acute/subacute severe cerebral venous thrombosis. Chin Med J (Engl) 2025:00029330-990000000-01460. [PMID: 40033789 DOI: 10.1097/cm9.0000000000003502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to analyses were used to evaluated associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyzed relationships between these changes and functional improvements. RESULTS A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs. 82.5%, OR = 2.98, P = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes (P <0.05). CONCLUSION Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov, NCT05990894.
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Affiliation(s)
- Shimin Hu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
- Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Yaqin Gu
- Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
- Intracranial Hypertension & Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Tingyu Zhao
- Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
- Intracranial Hypertension & Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Kaiyuan Zhang
- Department of Radiology & Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Jingkai Li
- Department of Radiology & Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Chen Zhou
- Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China
| | - Haiqing Song
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Zhi Liu
- Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Xunming Ji
- Intracranial Hypertension & Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
- Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Jiangang Duan
- Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
- Intracranial Hypertension & Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
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13
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Hansen SB, Dreyer AF, Jørgensen NT, Al-Jorani H, Bislev LS, Boesen VB, Borresen SW, Christensen LL, Glintborg D, Hauge EM, Hetland ML, Jensen RC, Just SA, Keller KK, Klose M, Laugesen K, Locht H, Lund ML, Stankovic J, Stewart PM, Tei RMH, Voss A, Feldt-Rasmussen U, Jørgensen JOL, Andersen MS. Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone. JAMA Netw Open 2025; 8:e251029. [PMID: 40100216 PMCID: PMC11920843 DOI: 10.1001/jamanetworkopen.2025.1029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 01/10/2025] [Indexed: 03/20/2025] Open
Abstract
Importance The widespread use of glucocorticoid (GC) therapy may result in GC-induced adrenal insufficiency (GIAI), but the prevalence and clinical implications remain uncertain. Objective To ascertain the prevalence and symptoms of GIAI. Design, Setting, and Participants Cross-sectional multicenter study at 3 Danish hospitals. Baseline data were collected March 2021 to March 2024 from an ongoing randomized clinical trial. Participants were patients with polymyalgia rheumatica and/or giant cell arteritis who were investigated a median (IQR) of 39 (25-62) days after planned cessation of prednisolone treatment. Exposure Prednisolone treatment a median (IQR) of 13 (10-20) months in duration. Main outcomes and measures Primary outcome GIAI was defined as a stimulated plasma cortisol level less than 420 nmol/L in response to a short 250 μg corticotropin test (SST). Secondary outcomes were adrenal insufficiency symptoms assessed by the Addison disease-specific quality of life questionnaire (AddiQoL-30), body composition, and muscle function. Results Of 267 patients included (145 female [55%]; median [IQR] age 73 [68-78] years), 5 (1.9%; 95% CI, 0.8%-4.3%) had GIAI, whereas 75 (34%; 95% CI, 28%-41%) had symptoms compatible with adrenal insufficiency defined by an AddiQoL-30 score 85 or lower (symptomatic group). The symptomatic group had lower basal cortisol levels compared with the asymptomatic group (263 nmol/L; 95% CI, 242-283 nmol/L vs 309 nmol/L; 95% CI, 295-324 nmol/L; P < .001). Factors associated with a low AddiQoL-30 score included female sex (prevalence ratio [PR], 1.68; 95% CI, 1.13-2.51), increased body fat percentage (PR, 2.33; 95% CI, 1.21-4.50), reduced handgrip strength (PR, 2.71; 95% CI, 1.44-5.10) and low Short Physical Performance Battery score (PR, 2.78; 95% CI, 1.42-5.42). Conclusions and Relevance This cross-sectional study of 267 patients with polymyalgia rheumatica or giant cell arteritis found a GIAI prevalence of 1.9% after cessation of prednisolone. This is much lower than previously reported and speaks against routine screening, which should be restricted to patients with overt symptoms. The high prevalence of symptoms of adrenal insufficiency in association with lower basal cortisol levels substantiate the clinical challenges of steroid withdrawal and merit future research.
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Affiliation(s)
- Simon Bøggild Hansen
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark
- Aarhus University, Department of Clinical Medicine, Aarhus, Denmark
| | - Anja Fenger Dreyer
- Odense University Hospital, Department of Endocrinology, Odense, Denmark
- University of Southern Denmark, Research Unit OPEN, Department of Clinical Research, Odense, Denmark
| | - Nanna Thurmann Jørgensen
- University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen, Denmark
- Copenhagen University Hospital, Rigshospitalet, Department of Nephrology and Endocrinology, Copenhagen, Denmark
| | - Hajir Al-Jorani
- Odense University Hospital, Department of Endocrinology, Odense, Denmark
- University of Southern Denmark, Research Unit OPEN, Department of Clinical Research, Odense, Denmark
| | - Lise Sofie Bislev
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark
- Aarhus University, Department of Clinical Medicine, Aarhus, Denmark
- Randers Hospital, Department of Internal Medicine, Randers, Denmark
| | - Victor Brun Boesen
- Copenhagen University Hospital, Rigshospitalet, Department of Nephrology and Endocrinology, Copenhagen, Denmark
| | - Stina Willemoes Borresen
- Copenhagen University Hospital, Rigshospitalet, Department of Nephrology and Endocrinology, Copenhagen, Denmark
| | - Louise Lehmann Christensen
- Odense University Hospital, Department of Endocrinology, Odense, Denmark
- University of Southern Denmark, Research Unit OPEN, Department of Clinical Research, Odense, Denmark
| | - Dorte Glintborg
- Odense University Hospital, Department of Endocrinology, Odense, Denmark
| | - Ellen Margrethe Hauge
- Aarhus University, Department of Clinical Medicine, Aarhus, Denmark
- Aarhus University Hospital, Department of Rheumatology, Aarhus, Denmark
| | - Merete Lund Hetland
- University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen, Denmark
- Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark
| | | | - Søren Andreas Just
- Svendborg Hospital–Odense University Hospital, Department of Medicine, Section of Rheumatology, Svendborg, Denmark
| | - Kresten Krarup Keller
- Aarhus University, Department of Clinical Medicine, Aarhus, Denmark
- Aarhus University Hospital, Department of Rheumatology, Aarhus, Denmark
| | - Marianne Klose
- Copenhagen University Hospital, Rigshospitalet, Department of Nephrology and Endocrinology, Copenhagen, Denmark
| | - Kristina Laugesen
- Aarhus University Hospital, Department of Clinical Epidemiology, Aarhus, Denmark
- Aarhus University Hospital, Department of Clinical Biochemistry, Aarhus, Denmark
| | - Henning Locht
- Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark
| | - Marie Louise Lund
- Copenhagen University Hospital, Rigshospitalet, Department of Nephrology and Endocrinology, Copenhagen, Denmark
| | - Jelena Stankovic
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark
- Aarhus University, Department of Clinical Medicine, Aarhus, Denmark
| | - Paul M. Stewart
- University of Leeds, Faculty of Medicine and Health, Leeds, United Kingdom
| | - Randi Maria Hanghøj Tei
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark
| | - Anne Voss
- Odense University Hospital, Department of Rheumatology, Odense, Denmark
| | - Ulla Feldt-Rasmussen
- University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen, Denmark
- Copenhagen University Hospital, Rigshospitalet, Department of Nephrology and Endocrinology, Copenhagen, Denmark
| | - Jens Otto L. Jørgensen
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark
- Aarhus University, Department of Clinical Medicine, Aarhus, Denmark
| | - Marianne Skovsager Andersen
- Odense University Hospital, Department of Endocrinology, Odense, Denmark
- University of Southern Denmark, Research Unit OPEN, Department of Clinical Research, Odense, Denmark
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14
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Moussally M, Paski SC, Cohen B, Holubar SD. Preoperative Optimization of Crohn's Patients before Abdominopelvic Surgery. Clin Colon Rectal Surg 2025; 38:85-95. [PMID: 39944311 PMCID: PMC11813612 DOI: 10.1055/s-0044-1786380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/27/2025]
Abstract
In this article, we review and identify modifiable risk factors associated with postoperative complications of Crohn's disease. We highlight the importance of factors such as nutrition, corticosteroids, immunomodulators, abscesses, ideal timing of surgery, and biologic and small-molecule therapy on surgical outcomes. Herein, we discuss the strategies for attenuating these risk factors. Special consideration is given to venous thromboembolism prophylaxis in this patient population.
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Affiliation(s)
- Moustafa Moussally
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Shirley C. Paski
- Department of Gastroenterology, Hepatology, and Human Nutrition, Cleveland, Ohio
| | - Benjamin Cohen
- Department of Gastroenterology, Hepatology, and Human Nutrition, Cleveland, Ohio
| | - Stefan D. Holubar
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
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15
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Zhang B, Yang N, Li L. Bullous pemphigoid and hypercoagulability: a review. Expert Rev Clin Immunol 2025; 21:323-332. [PMID: 39772971 DOI: 10.1080/1744666x.2025.2450766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 12/25/2024] [Accepted: 01/05/2025] [Indexed: 01/11/2025]
Abstract
INTRODUCTION Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies against hemidesmosomal proteins in the basal membrane zone. The presence of a high incidence of thrombotic events has led to the identification of a hypercoagulable state in BP patients. AREAS COVERED This review highlights the interactions between coagulation and immune-inflammatory responses based on the currently available literature, as well as individual changes in characteristic coagulation parameters in BP. This review is based on publications up to August 2024 that were retrieved by a selective search in the PubMed database. EXPERT OPINION The hypercoagulable state and bullous pemphigoid (BP) have a reciprocally enhancing effect on each other. For clinicians, it is crucial to closely monitor the fluctuations in circulating coagulation markers among BP patients, such as D-dimer, fibrinogen, and fibrin degradation products (FDP). Furthermore, considering the interplay between coagulation and immune-inflammatory responses in BP, targeting the shared pathways in treatment strategies could be beneficial for patients who exhibit both BP and a hypercoagulable state.
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Affiliation(s)
- Bingjie Zhang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Nan Yang
- Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Li Li
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
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16
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Liu Z, Zhang L, Peng W, Chen Q, Hou Y, Zhan L, Li G. Advances in sulodexide-based long-term anticoagulation for a myasthenia gravis patient with giant thymoma. Front Pharmacol 2025; 16:1543612. [PMID: 40078295 PMCID: PMC11900545 DOI: 10.3389/fphar.2025.1543612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 01/20/2025] [Indexed: 03/14/2025] Open
Abstract
This case report describes a geriatric male patient with myasthenia gravis (MG) secondary to giant thymoma, presenting with progressive muscle weakness and ptosis. The diagnosis of MG was confirmed through pathology, imaging, and laboratory evaluations. Considering the significant surgical risks associated with the giant thymoma, adjuvant chemotherapy was initiated. Unfortunately, 2 weeks following chemotherapy, the patient developed acute respiratory failure and sudden loss of consciousness. Emergency endotracheal intubation was performed, and he was then transferred to the intensive care unit (ICU) and treated with immunoglobulin, plasmapheresis, prednisone, and pyridostigmine. During ICU hospitalization, the patient developed severe lower limb edema accompanied by increased skin temperature, particularly on the left side. Ultrasound imaging confirmed extensive thrombosis in the left iliac and femoral veins, with thrombosis involving 50%-67% of the venous lumen. To prevent the risk of pulmonary embolism (PE), an inferior vena cava filter was implanted, and low-molecular weight heparin (LMWH) was prescribed for anticoagulation. Unfortunately, the patient later experienced intermittent melena and heparin-induced thrombocytopenia (HIT), with hemoglobin levels decreasing to 55 g/L and platelet counts decreasing to 57 × 109/L. Given the adverse events associated with LMWH, sulodexide (SDX) was substituted as a novel anticoagulant with multiple benefits, including reduced thrombosis and bleeding risk, anti-inflammatory effects, and vascular endothelium protection. SDX demonstrated excellent efficacy and safety, with no adverse effects observed during the 3-year follow-up period. In conclusion, SDX should be considered an ideal potential option for long-term anticoagulation in patients with complex conditions such as MG with both thrombotic and bleeding risks.
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Affiliation(s)
- Zhou Liu
- Department of Intensive Care Unit, Renmin Hospital of Wuhan University, Wuhan, China
| | - Liang Zhang
- Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Peng
- Department of Intensive Care Unit, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qianqian Chen
- Department of Intensive Care Unit, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yanguang Hou
- Department of Intensive Care Unit, Renmin Hospital of Wuhan University, Wuhan, China
| | - Liying Zhan
- Department of Intensive Care Unit, Renmin Hospital of Wuhan University, Wuhan, China
| | - Guang Li
- Department of Intensive Care Unit, Renmin Hospital of Wuhan University, Wuhan, China
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Svalastoga M, Larsen TL, Brekke J, Enden T, Frøen H, Garresori H, Jacobsen EM, Porojnicu AC, Ree AH, Torfoss D, Velle EO, Wik HS, Ghanima W, Sandset PM, Dahm AEA. Effect of drug interactions with apixaban on clinical outcomes in cancer patients with venous thromboembolism. Front Oncol 2025; 15:1520725. [PMID: 39931081 PMCID: PMC11807833 DOI: 10.3389/fonc.2025.1520725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/02/2025] [Indexed: 02/13/2025] Open
Abstract
Introduction It is unclear how drug-interaction with apixaban influences recurrent venous thromboembolism (VTE) and bleedings in cancer patients. Methods A post-hoc analysis of a single-arm interventional clinical trial on apixaban treatment of cancer patients with VTE to investigate whether the occurrence of any of the endpoints could be associated with the concurrent use of an interacting drug. Drugs taken by the patients during the trial period were categorized as either increasing bleeding risk, increasing thrombosis risk, both or neither. Results 298 patients were divided into groups based on whether they used no interacting drugs (controls, n=74), drugs increasing bleeding risk (n=55), drugs increasing thrombosis risk (n=8), or both (n=161). Odds ratios (OR) were calculated for recurrent VTE, clinically relevant non-major bleeding (CRNMB), and major bleeding during the 36-month follow-up period. Each patient took a median of 13 different drugs over the study period. 67% of the patients used drugs expected to both increase bleeding and thrombosis. The use of fluconazole appeared associated with CRNMB (OR 3.6, 95% confidence interval (CI) 0.99-13), but not with major bleeding (OR 0.56, 95% CI 0.06 - 4.8). Non-steroid anti-inflammatory drugs were not associated with CRNMB (OR 1.0, 95% CI 0.25-4.1) or major bleedings (OR 0.72, 95% CI 0.14 - 3.6). Use of antiplatelet therapy was not associated with CRNMB (OR 0.75, 95% CI, 0.22 - 2.58) or major bleeding (OR 0.2, 95% CI, 0.02-1.6). There were no major bleedings in 23 patients using aprepitant nor in the 10 patients taking macrolides. We found no association between drugs and recurrent VTE, except that there were no recurrent VTE in 19 patients using bevacizumab. Conclusions Despite the high number of drugs taken that could potentially interact with apixaban, none were found to clearly influence clinical outcomes, except that fluconazole may increase the risk of CRNMB.
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Affiliation(s)
- Marte Svalastoga
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trine-Lise Larsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Haematology, Akershus University Hospital, Lørenskog, Norway
| | - Jorunn Brekke
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Tone Enden
- Department of Radiology, Oslo University Hospital, Oslo, Norway
| | - Hege Frøen
- Department of Medicine, Baerum Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | - Herish Garresori
- Department of Oncology, Stavanger University Hospital, Stavanger, Norway
| | | | | | - Anne Hansen Ree
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Dag Torfoss
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Elin Osvik Velle
- Department of Medicine, Volda Hospital, Møre and Romsdal Hospital Trust Volda, Volda, Norway
| | | | - Waleed Ghanima
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Clinic of Internal Medicine, Østfold Hospital, Grålum, Norway
| | - Per Morten Sandset
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Haematology, Oslo University Hospital, Oslo, Norway
| | - Anders Erik Astrup Dahm
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Haematology, Akershus University Hospital, Lørenskog, Norway
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Ngo D, Chen J, Nguyen C, Choi K, Pullarkat V. Patterns of interventions for central venous catheter-associated deep vein thrombosis and outcomes in cancer patients. J Oncol Pharm Pract 2025; 31:12-16. [PMID: 38166462 DOI: 10.1177/10781552231219995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
PURPOSE This letter evaluated the impact of different management strategies, specifically the presence or absence of therapeutic anticoagulation, on clinical outcomes for central venous catheter (CVC)-associated deep vein thrombosis (DVT) in cancer patients. METHODS One-hundred ninety-eight adult cancer patients with a confirmed CVC-associated DVT diagnosis from February 2013 and February 2021 were included. RESULTS Incidence of symptomatic recurrent venous thromboembolism (VTE) was similar between patients who received therapeutic anticoagulation and those who did not (14% vs 16%, p = 0.807). In addition, therapeutic anticoagulation did not significantly alter the incidence of grade 3 and above bleeding events despite most patients having hematologic malignancies (9% vs 8%, p = 0.826). CONCLUSION AND RELEVANCE Therapeutic anticoagulation was not associated with a reduction in the incidence of recurrent VTE or increase the incidence of bleeding in adult cancer patients following a CVC-associated DVT diagnosis.
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Affiliation(s)
- Dat Ngo
- Department of Pharmacy, City of Hope, Duarte, CA, USA
| | - Jason Chen
- Department of Pharmacy, City of Hope, Duarte, CA, USA
| | - Chris Nguyen
- Department of Pharmacy, City of Hope, Duarte, CA, USA
| | - Kathy Choi
- Department of Pharmacy, City of Hope, Duarte, CA, USA
| | - Vinod Pullarkat
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA
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19
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Rudman Y, Michaelis M, Shimon I, Dotan I, Shochat T, Kushnir S, Fleseriu M, Akirov A. Can we predict the risk of venous thromboembolism in patients with Cushing's syndrome: a nationwide cohort analysis. Pituitary 2024; 28:10. [PMID: 39729122 DOI: 10.1007/s11102-024-01482-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/05/2024] [Indexed: 12/28/2024]
Abstract
PURPOSE Patients with Cushing's syndrome (CS) have an increased venous thromboembolism (VTE) risk with most studies focusing on the perioperative period. The purpose of this study was to assess the 5-year VTE risk and identify predictors of VTE at CS diagnosis. METHODS A comparative nationwide retrospective cohort study of 609 patients (mean age 48.1 ± 17.2 years, 65.0% women) with CS, and 3018 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS and adrenal cancer were excluded. The time-to-event of pulmonary embolism (PE) or deep vein thrombosis (DVT) within 5 years of CS diagnosis was examined. VTE risk was calculated with death as competing event. RESULTS VTE occurred in 16 cases (2.6%), compared to 17 (0.56%) controls (hazard ratio [HR] 4.71, 95% CI, 2.38-9.33). The 5-year HRs for PE and DVT were 7.47 (95% CI, 2.66-20.98) and 3.32 (95% CI, 1.36-8.12), respectively. After excluding patients and controls with current or prior malignancy the risk for VTE was 7.57 (95% CI, 2.98-19.20). Patients with CS ≥ 60 years at diagnosis (HR, 3.49; 95% CI, 1.30-9.35), with hypertension (HR, 5.53; 95% CI, 1.26-24.27), ischemic heart disease (HR, 3.60; 95% CI, 1.25-10.36), kidney disease (HR, 4.85; 95% CI, 1.39-16.90), or VTE event prior to CS diagnosis (HR, 33.65; 95% CI, 10.07-112.42) had an increased risk of VTE within five years. CONCLUSIONS In this large cohort of patients with CS, the 5-year VTE risk was 5 times higher compared with matched controls. Key baseline predictors included age ≥ 60, hypertension, heart/kidney disease, and prior VTE.
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Affiliation(s)
- Yaron Rudman
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, 49100, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Michal Michaelis
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Internal Medicine E, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
| | - Ilan Shimon
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, 49100, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Idit Dotan
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, 49100, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tzippy Shochat
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Biostatistics Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Shiri Kushnir
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Research Authority, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Maria Fleseriu
- Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
| | - Amit Akirov
- Institute of Endocrinology, Beilinson Hospital, Rabin Medical Center, 49100, Petah Tikva, Israel.
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Cenerini G, Chimera D, Pagnini M, Bazzan E, Conti M, Turato G, Celi A, Neri T. The Intricate Relationship Between Pulmonary Fibrosis and Thrombotic Pathology: A Narrative Review. Cells 2024; 13:2099. [PMID: 39768190 PMCID: PMC11674501 DOI: 10.3390/cells13242099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk-benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.
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Affiliation(s)
- Giovanni Cenerini
- UO Pneumologia, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, Italy; (G.C.); (D.C.)
| | - Davide Chimera
- UO Pneumologia, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, Italy; (G.C.); (D.C.)
| | - Marta Pagnini
- Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy; (M.P.); (T.N.)
| | - Erica Bazzan
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy; (E.B.); (M.C.); (G.T.)
| | - Maria Conti
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy; (E.B.); (M.C.); (G.T.)
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy
| | - Graziella Turato
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy; (E.B.); (M.C.); (G.T.)
| | - Alessandro Celi
- Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy; (M.P.); (T.N.)
| | - Tommaso Neri
- Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy; (M.P.); (T.N.)
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21
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Liu Y, Tang Y, Le WB, Chen D, Liang D, Xu F, Liang S, Zhong Y, Zeng C. The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy. Ren Fail 2024; 46:2374448. [PMID: 38973428 PMCID: PMC11232635 DOI: 10.1080/0886022x.2024.2374448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/25/2024] [Indexed: 07/09/2024] Open
Abstract
BACKGROUND Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.
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Affiliation(s)
- Yunyun Liu
- Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yujie Tang
- Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei-Bo Le
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Dacheng Chen
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Dandan Liang
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Feng Xu
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Shaoshan Liang
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yongzhong Zhong
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Caihong Zeng
- Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Yu J, Fu L, Jin G, Gao F, Ding L, Hong L, Lv S, Jin J, Tang L, Feng W, Zhang K, Xu C. Immune thrombocytopenia increases the risk of thrombosis: A two-sample Mendelian randomization study. Int J Cardiol 2024; 414:132417. [PMID: 39098611 DOI: 10.1016/j.ijcard.2024.132417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 07/19/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Immune thrombocytopenia (ITP) is a prevalent autoimmune bleeding disorder, with the primary objective of treatment being the prevention of bleeding. Clinical investigations have indicated that individuals with ITP face an elevated risk of thrombosis, and the occurrence of thromboembolic events in ITP patients can be attributed to a multitude of factors. However, establishing a definitive causal relationship between ITP and thrombosis remains challenging. METHODS A two-sample Mendelian randomization (MR) study utilizing summary data from FinnGen consortium and UK Biobank was undertaken to investigate the causal association between ITP and thrombosis. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary analyses were conducted using the MR-Egger, weighted median, and MR-PRESSO approaches. RESULTS Based on IVW method, there was a statistically significant but small positive correlation between ITP and thrombosis. Specifically, ITP patients exhibited a suggestive positive correlation with myocardial infarction and deep-vein thrombosis. However, our investigation did not identify any causal relationship between ITP and cerebral infarction, arterial embolism, other arterial embolisms, pulmonary embolism, thrombophlebitis, or portal vein thrombosis. Sensitivity analyses further confirmed the accuracy and robustness of these findings. CONCLUSIONS This study presents empirical support for the causal relationship between ITP and thrombosis. It is important to note that a diminished platelet count does not serve as a preventive measure against thrombus formation. Consequently, when managing a newly diagnosed ITP patient, clinicians need to be aware that there is a slight elevation in the risk of thrombosis during treatment.
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MESH Headings
- Humans
- Mendelian Randomization Analysis
- Purpura, Thrombocytopenic, Idiopathic/epidemiology
- Purpura, Thrombocytopenic, Idiopathic/complications
- Purpura, Thrombocytopenic, Idiopathic/genetics
- Purpura, Thrombocytopenic, Idiopathic/diagnosis
- Purpura, Thrombocytopenic, Idiopathic/blood
- Thrombosis/epidemiology
- Thrombosis/etiology
- Thrombosis/diagnosis
- Thrombosis/genetics
- Risk Factors
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Affiliation(s)
- Jieni Yu
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Leihua Fu
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Gan Jin
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China; Department of Vascular and Hernia Surgery, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Feidan Gao
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Lina Ding
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Li Hong
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Shanmei Lv
- Department of Laboratory, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Jing Jin
- Department of Hematology, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Liming Tang
- Department of Vascular and Hernia Surgery, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Weiying Feng
- Department of Vascular and Hernia Surgery, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China
| | - Kejie Zhang
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen City,Fujian Province, People's Republic of China
| | - Chao Xu
- Department of Vascular and Hernia Surgery, Shaoxing People's Hospital. Shaoxing City, Zhejiang Province, People's Republic of China.
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23
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Ratnasamy PP, Diatta F, Allam O, Kauke-Navarro M, Grauer JN. Risk of Postoperative Complications After Total Hip and Total Knee Arthroplasty in Behcet Syndrome Patients. J Am Acad Orthop Surg Glob Res Rev 2024; 8:01979360-202410000-00005. [PMID: 39392934 PMCID: PMC11469891 DOI: 10.5435/jaaosglobal-d-24-00040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 07/22/2024] [Accepted: 08/10/2024] [Indexed: 10/13/2024]
Abstract
BACKGROUND Behcet syndrome (BS), a multisystem autoimmune disorder, has unclear effects on outcomes after total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study assessed the relative risk of perioperative adverse events in patients with BS. METHODS This retrospective cohort study used the PearlDiver M157Ortho data set, a large national administrative database. Total hip arthroplasty and TKA patients with BS were identified and matched 1:4 to those without BS based on patient age, sex, Elixhauser Comorbidity Index scores, and procedure performed (THA or TKA). The incidence of 90-day adverse events was determined and compared by multivariate analysis. 5-year survival to revision surgeries was assessed and compared with the log-rank test. RESULTS After matching, 282 THA/TKA patients with BS were identified and compared with 1127 without BS. On multivariate analysis, patients with BS were at independently greater risk of aggregated any (odds ratio [OR] 2.16, P < 0.0001), serious (OR 1.78, P = 0.0051), and minor (OR 2.39, P < 0.0001) adverse events compared with those without BS. No significant difference was observed in 5-year survival to revision surgery (P = 0.3). CONCLUSIONS Patients with BS undergoing THA or TKA experienced markedly greater 90-day postoperative adverse events. The findings underscore the need for optimized perioperative management for patients with BS undergoing arthroplasty.
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Affiliation(s)
- Philip P. Ratnasamy
- From the Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT
| | - Fortunay Diatta
- From the Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT
| | - Omar Allam
- From the Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT
| | - Martin Kauke-Navarro
- From the Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT
| | - Jonathan N. Grauer
- From the Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT
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24
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Kępski J, Szmit S, Lech-Marańda E. Time Relationship between the Occurrence of a Thromboembolic Event and the Diagnosis of Hematological Malignancies. Cancers (Basel) 2024; 16:3196. [PMID: 39335167 PMCID: PMC11430228 DOI: 10.3390/cancers16183196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/07/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
OBJECTIVES Venous and arterial thromboembolism (VTE/ATE) often coexist with onco-hematologic diagnosis. This study aimed to assess the time relationship between the diagnosis of VTE/ATE and blood cancers. The second aim was to identify VTE/ATE risk factors related to the type of hematology disease and cardiac history. METHODS A total of 1283 patients underwent cardio-oncology evaluation at the Institute of Hematology and Transfusion Medicine in Warsaw from March 2021 through March 2023 (2 years), and 101 (7.8%) cases were identified with VTE/ATE. RESULTS ATE compared with VTE significantly occurred more often before the diagnosis and treatment of hematologic malignancy: 33/47 (70.2%) vs. 15/54 (27.8%), p < 0.0001. The risk of a VTE episode is exceptionally high in the first months after the diagnosis of an onco-hematological disease and the initiation of anticancer treatment. The higher frequency of VTE was associated with acute myeloid leukemia (17 cases/270 patients/6.30%/p = 0.055), acute lymphocytic leukemia (7 cases/76 patients/9.21%/p = 0.025), and chronic myeloproliferative disease (7 cases/48 patients/14.58%/p = 0.0003). Only the risk of VTE was significantly increased before (OR = 6.79; 95% CI: 1.85-24.95; p = 0.004) and after diagnosis of myeloproliferative disease (OR = 3.12; 95% CI: 1.06-9.16; p = 0.04). CONCLUSIONS ATEs occur more often than VTE before a diagnosis of blood cancer. The risk of VTE is exceptionally high before and after diagnosis of chronic myeloproliferative disease.
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Affiliation(s)
- Jarosław Kępski
- Department of Cardio-Oncology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Sebastian Szmit
- Department of Cardio-Oncology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Ewa Lech-Marańda
- Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
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Bloom CI, Yang F, Hubbard R, Majeed A, Wedzicha JA. Association of Dose of Inhaled Corticosteroids and Frequency of Adverse Events. Am J Respir Crit Care Med 2024; 211:54-63. [PMID: 39088770 PMCID: PMC11755354 DOI: 10.1164/rccm.202402-0368oc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 08/01/2024] [Indexed: 08/03/2024] Open
Abstract
BACKGROUND Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment and significantly improve morbidity and mortality. Adverse effects of oral corticosteroids are well documented, but less is known about ICS. METHODS We conducted observational studies in adults with asthma using two different UK nationwide datasets: Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD. The exposure was incident ICS; the outcomes were major adverse cardiac events (MACE), arrhythmia, pulmonary embolism (PE) and pneumonia over 12-months. Our main analyses used a cohort method with stabilized inverse probability treatment weighting to balance confounding between exposed and unexposed patients. Secondary analyses included nested case-control studies, and self-controlled case series. ICS was treated both as a categorical and continuous variable. Absolute risk was estimated using weighted flexible parametric models. FINDINGS From 162,202 patients in our main cohort, there was an association with all outcomes at medium daily ICS dose or higher (HR, 95%CI at 201-599mcg: MACE=2.63, 1.66-4.15, arrhythmia=2.21, 1.60-3.04, PE=2.10, 1.37-3.22, pneumonia=2.25, 1.77-2.85; at ≥600mcg: MACE=4.63, 2.62-8.17, arrhythmia=2.91, 1.72-4.91, PE=3.32, 1.69-6.50, pneumonia=4.09, 2.98-5.60). There were no associations with lower doses of ICS. Secondary analyses produced similar results. The number needed to harm (95%CI) using 12-months of ICS 201-599mcg: MACE=473 (344-754), arrhythmia=567 (395-1006), PE=1221 (744-3388) and pneumonia=230 (177-327) and using ICS ≥600mcg: MACE=224 (148-461), arrhythmia=396 (228-1523), PE=577 (309-4311), pneumonia=93 (69-141). INTERPRETATION Short-term use of low dose ICS was not associated with adverse effects. Moderate-high daily ICS doses were associated with an increased risk, but low-frequency, of cardiovascular events, pulmonary embolism and pneumonia. It is important for clinicians to adhere to guideline recommendations to use the lowest effective ICS dose. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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Affiliation(s)
- Chloë I Bloom
- Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland;
| | - Freda Yang
- Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Richard Hubbard
- Nottingham University, Nottingham, United Kingdom of Great Britain and Northern Ireland
| | - Azeem Majeed
- Imperial College London, School of Public Health, London, United Kingdom of Great Britain and Northern Ireland
| | - Jadwiga A Wedzicha
- Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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He ML, Zheng Y, Tian SX. Cronkhite-Canada syndrome complicated with pulmonary embolism: A case report. World J Clin Cases 2024; 12:4820-4826. [PMID: 39070830 PMCID: PMC11235495 DOI: 10.12998/wjcc.v12.i21.4820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/23/2024] [Accepted: 06/11/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Cronkhite-Canada syndrome (CCS) is a rare disease, that causes gastrointestinal polyps, ectodermal abnormalities, and gastrointestinal symptoms. CCS is prone to thromboembolism, but clinical workers have not yet established a clinical consciousness of preventing thromboembolism. The present case illustrates pulmonary embolism (PE) complicated by CCS. CASE SUMMARY A 46-year-old male patient presented with mucus, purulent, and bloody stool. Ectodermal changes included skin pigmentation, alopecia, and nail dystrophy. Colonoscopy revealed the presence of multiple polyps. After a comprehensive evaluation, the patient was diagnosed with CCS. During the disease, he was also diagnosed with pulmonary embolism, Riehl's melanosis, and intestinal flora imbalance. After symptomatic treatment with omeprazole, mesalazine, rivaroxaban, nutritional support, and regulation of intestinal flora, the patient's symptoms were significantly relieved. CONCLUSION CCS complicated with PE was reported for the first time in China in this study. Despite the fact that CCS is extremely rare, patients with CCS should be classified as a high-risk venous thromboembolism (VTE) population, and emphasis should be placed on venous thromboembolism risk assessment and stratification, deep venous thromboembolism screening, prevention of VTE, and careful long-term follow-up.
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Affiliation(s)
- Mao-Lang He
- College of Medicine, Shihezi University, Shihezi 832099, Xinjiang Uygur Autonomous Region, China
| | - Yong Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
| | - Shu-Xin Tian
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
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Tian H, Xie C, Teng B, Zeng Q, Zhao Y, Li F, Jiang C, Chen Z. The genetic effects of hormones modulated by the Pituitary-Thyroid/Adrenal/Gonadal axis on the risk of developing venous thromboembolism: a mendelian randomization study. BMC Cardiovasc Disord 2024; 24:383. [PMID: 39054435 PMCID: PMC11270940 DOI: 10.1186/s12872-024-04039-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 07/10/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. METHODS A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. RESULTS A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. CONCLUSIONS Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.
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Affiliation(s)
- Hao Tian
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China
| | - Chaozheng Xie
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Biyun Teng
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China
| | - Qiu Zeng
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China
| | - Yu Zhao
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China
| | - Fenghe Li
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China
| | - Chuli Jiang
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China
| | - Zheng Chen
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 N. Youyi Street, Chongqing, 400016, China.
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Sobiecka M, Siemion-Szczesniak I, Burakowska B, Kurzyna M, Dybowska M, Tomkowski W, Szturmowicz M. Sarcoidosis-associated pulmonary hypertension due to pulmonary arteries stenosis - a case report. BMC Pulm Med 2024; 24:346. [PMID: 39014431 PMCID: PMC11251360 DOI: 10.1186/s12890-024-03152-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 07/08/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND Sarcoidosis-associated pulmonary hypertension (SAPH) is listed in Group 5 of the clinical classification of pulmonary hypertension, due to its complex and multifactorial pathophysiology. The most common cause of SAPH development is advanced lung fibrosis with the associated destruction of the vascular bed, and/or alveolar hypoxia. However, a substantial proportion of SAPH patients (up to 30%) do not have significant fibrosis on chest imaging. In such cases, the development of pulmonary hypertension may be due to the lesions directly affecting the pulmonary vasculature, such as granulomatous angiitis, pulmonary veno-occlusive disease, chronic thromboembolism or external compression of vessels by enlarged lymph nodes. Based on the case of a 69-year-old female who developed SAPH due to pulmonary arteries stenosis, diagnostic difficulties and therapeutic management are discussed. CASE PRESENTATION The patient, non-smoking female, diagnosed with stage II sarcoidosis twelve years earlier, presented with progressive dyspnoea on exertion, dry cough, minor haemoptysis and increasing oedema of the lower limbs. Computed tomography pulmonary angiography (CTPA) showed complete occlusion of the right upper lobe artery and narrowing of the left lower lobe artery, with post-stenotic dilatation of the arteries of the basal segments. The vascular pathology was caused by adjacent, enlarged lymph nodes with calcifications and fibrotic tissue surrounding the vessels. Pulmonary artery thrombi were not found. The patient was treated with systemic corticosteroid therapy and subsequently with balloon pulmonary angioplasty. Partial improvement in clinical status and hemodynamic parameters has been achieved. CONCLUSIONS An appropriate screening strategy is required for early detection of pulmonary hypertension in sarcoidosis patients. Once SAPH diagnosis is confirmed, it is crucial to determine the appropriate phenotype of pulmonary hypertension and provide the most effective treatment plan. Although determining SAPH phenotype is challenging, one should remember about the possibility of pulmonary arteries occlusion.
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Affiliation(s)
- Malgorzata Sobiecka
- 1 st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland.
| | - Izabela Siemion-Szczesniak
- 1 st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland
| | - Barbara Burakowska
- Department of Radiology, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland
| | - Marcin Kurzyna
- Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology European Health Center Otwock, Medical Centre for Postgraduate Education, Otwock, Poland
| | - Malgorzata Dybowska
- 1 st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland
| | - Witold Tomkowski
- 1 st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland
| | - Monika Szturmowicz
- 1 st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, Warsaw, 01-138, Poland
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30
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Coutinho JM, van de Munckhof A, Aguiar de Sousa D, Poli S, Aaron S, Arauz A, Conforto AB, Krzywicka K, Hiltunen S, Lindgren E, Sánchez van Kammen M, Shu L, Bakchoul T, Belder R, van den Berg R, Boumans E, Cannegieter S, Cano-Nigenda V, Field TS, Fragata I, Heldner MR, Hernández-Pérez M, Klok FA, Leker RR, Lucas-Neto L, Molad J, Nguyen TN, Saaltink DJ, Saposnik G, Sharma P, Stam J, Thijs V, van der Vaart M, Werring DJ, Wong Ramos D, Yaghi S, Yeşilot N, Tatlisumak T, Putaala J, Jood K, Arnold M, Ferro JM. Reducing the global burden of cerebral venous thrombosis: An international research agenda. Int J Stroke 2024; 19:599-610. [PMID: 38494462 PMCID: PMC11292977 DOI: 10.1177/17474930241242266] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/04/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.
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Affiliation(s)
- Jonathan M Coutinho
- Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
| | - Anita van de Munckhof
- Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
| | - Diana Aguiar de Sousa
- Stroke Center, Centro Hospitalar Universitário Lisboa Central, Institute of Anatomy, Faculdade de Medicina, Universidade de Lisboa, and L Lopes Lab, Instituto de Medicina Molecular JLA, Lisbon, Portugal
| | - Sven Poli
- Department of Neurology & Stroke, University of Tübingen, Tübingen, Germany
- Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
| | | | - Antonio Arauz
- Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City, Mexico
| | - Adriana B Conforto
- LIM-44, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Katarzyna Krzywicka
- Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
| | - Sini Hiltunen
- Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Erik Lindgren
- Department of Neurology, Sahlgrenska University Hospital and Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Mayte Sánchez van Kammen
- Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
| | - Liqi Shu
- Brown University, Providence, RI, USA
| | - Tamam Bakchoul
- Centre for Clinical Transfusion Medicine, Medical Faculty of Tübingen, University of Tübingen, Tübingen, Germany
| | - Rosalie Belder
- Netherlands Thrombosis Foundation, Voorschoten, The Netherlands
| | - René van den Berg
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
| | | | - Suzanne Cannegieter
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Vanessa Cano-Nigenda
- Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City, Mexico
| | - Thalia S Field
- Vancouver Stroke Program, Division of Neurology, University of British Columbia, Vancouver, BC, Canada
| | - Isabel Fragata
- Stroke Center, Centro Hospitalar Universitário Lisboa Central, Institute of Anatomy, Faculdade de Medicina, Universidade de Lisboa, and L Lopes Lab, Instituto de Medicina Molecular JLA, Lisbon, Portugal
- NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Mirjam R Heldner
- Inselspital Bern, University Hospital and University of Bern, Bern, Switzerland
| | | | - Frederikus A Klok
- Department of Medicine—Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
| | - Ronen R Leker
- Hadassah—Hebrew University Medical Center, Jerusalem, Israel
| | - Lia Lucas-Neto
- North Lisbon University Hospital Center and Lisbon Medical School, Lisbon, Portugal
| | | | | | | | - Gustavo Saposnik
- Stroke Outcomes & Decision Neuroscience Research Unit, University of Toronto, Toronto, ON, Canada
| | - Pankaj Sharma
- Royal Holloway University of London, London, United Kingdom
| | - Jan Stam
- Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
| | - Vincent Thijs
- Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
- Department of Medicine, The University of Melbourne, Parkville, VIC, Australia
| | | | - David J Werring
- UCL Queen Square Institute of Neurology, London, United Kingdom
| | - Diana Wong Ramos
- Portugal AVC-União de Sobreviventes, Familiares e Amigos, Portugal
| | | | - Nilüfer Yeşilot
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Turgut Tatlisumak
- Department of Neurology, Sahlgrenska University Hospital and Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Jukka Putaala
- Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Katarina Jood
- Department of Neurology, Sahlgrenska University Hospital and Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Marcel Arnold
- Inselspital Bern, University Hospital and University of Bern, Bern, Switzerland
| | - José M Ferro
- Hospital da Luz, University of Lisbon, Lisbon, Portugal
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Yafasova A, Fosbøl EL, Gustafsson F, Krintel SB, Kristensen SL, Schou M, Petersen JK, Sun G, Rossing K, Doi SN, Køber L, Butt JH. Long-Term Risk of VTE in Sarcoidosis: A Nationwide Cohort Study. Chest 2024; 166:136-145. [PMID: 38295951 DOI: 10.1016/j.chest.2024.01.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 01/20/2024] [Accepted: 01/23/2024] [Indexed: 02/26/2024] Open
Abstract
BACKGROUND Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse. RESEARCH QUESTION Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population? STUDY DESIGN AND METHODS Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE. RESULTS We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15). INTERPRETATION In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.
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Affiliation(s)
- Adelina Yafasova
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
| | - Emil L Fosbøl
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Finn Gustafsson
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Sophine B Krintel
- Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Søren L Kristensen
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Morten Schou
- Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, Denmark
| | - Jeppe K Petersen
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Guoli Sun
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Kasper Rossing
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Seiko N Doi
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Lars Køber
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Jawad H Butt
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Cardiology, Zealand University Hospital, Roskilde, Denmark
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Székely H, Tóth LM, Rancz A, Walter A, Farkas N, Sárközi MD, Váncsa S, Erőss B, Hegyi P, Miheller P. Anti-tumor Necrosis Factor Alpha Versus Corticosteroids: A 3-fold Difference in the Occurrence of Venous Thromboembolism in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis. J Crohns Colitis 2024; 18:773-783. [PMID: 37952112 PMCID: PMC11140625 DOI: 10.1093/ecco-jcc/jjad193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is complex, and the role of medication is not precisely defined. We aimed to assess the effects of anti-tumor necrosis factor alpha [anti-TNFα] drugs and conventional anti-inflammatory therapy, namely corticosteroids [CS], immunomodulators [IM], and 5-aminosalicylates [5-ASA] on VTE in IBD. METHODS A systematic search was performed in five databases on November 22, 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios [OR] with 95% confidence intervals [CI], using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS The quantitative analysis included 16 observational studies, with data from 91 322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE [proportion: 0.05, CI: 0.02-0.10], than patients treated with CS [proportion: 0.16, CI: 0.07-0.32], with OR = 0.42 [CI: 0.25-0.71]. IMs resulted in similar proportions of VTE compared with biologics [0.05, CI: 0.03-0.10], with OR = 0.94 [CI: 0.67-1.33]. The proportion of patients receiving 5-ASA having VTE was 0.09 [CI: 0.04-0.20], with OR = 1.00 [CI: 0.61-1.62]. CONCLUSIONS Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.
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Affiliation(s)
- Hajnal Székely
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Laura Mária Tóth
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Anett Rancz
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Hematology, Medical School, Semmelweis University, Budapest, Hungary
| | - Anna Walter
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Nelli Farkas
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | | | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Bálint Erőss
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Pál Miheller
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
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Myllylahti L, Niskanen L, Lassila R, Haukka J. A pharmacoepidemiological nested case-control study of risk factors for venous thromboembolism with the focus on diabetes, cancer, socioeconomic group, medications, and comorbidities. Diab Vasc Dis Res 2024; 21:14791641241236894. [PMID: 38904171 PMCID: PMC11193353 DOI: 10.1177/14791641241236894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/22/2024] Open
Abstract
OBJECTIVES A pharmacoepidemiological study to assess VTE risk factors in a diabetes-rich population. METHODS The study comprised 299,590 individuals. We observed 3450 VTEs and matched them with 15,875 controls using a nested case-control approach and collected data on comorbidities and prescriptions. By multivariable conditional logistic regression, we calculated ORs with 95%CIs for comorbidities and medications to evaluate their associations with VTE. RESULTS Diabetes (aOR 2.16; 95%CI 1.99-2.34), inflammatory bowel disease (1.84; 1.27-2.66), and severe psychiatric disorders (1.72; 1.43-2.05) had the strongest associations among the non-cancer comorbidities. Pancreatic (12.32; 7.11-21.36), stomach (8.57; 4.07-18.03), lung and bronchus (6.26; 4.16-9.43), and ovarian (6.72; 2.95-15.10) cancers were ranked as high-risk for VTE. Corticosteroids, gabapentinoids, psychotropic drugs, risedronic acid, and pramipexole were most strongly associated (aOR exceeding 1.5) with VTE. Insulin (3.86; 3.33-4.47) and sulphonylureas (2.62; 2.18-3.16) had stronger associations than metformin (1.65; 1.49-1.83). Statins and lercanidipine (0.78; 0.62-0.98) were associated with a lowered risk of VTE. CONCLUSIONS In this cohort, with 50% diabetes prevalence, pancreatic, stomach, lung and bronchus, and ovarian cancers were strongly associated with VTE. Corticosteroids, gabapentinoids, and psychotropic medications had the strongest associations with VTE among medications. This may be valuable for generating hypotheses for the further research. Lercanidipine may be a novel protective medication against VTE.
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Affiliation(s)
- Lasse Myllylahti
- Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
| | - Leo Niskanen
- Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
- Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
| | - Riitta Lassila
- Unit of Coagulation Disorders, Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
- Research Program Unit in Systems Oncology, University of Helsinki, Helsinki, Finland
- The Finnish Institute of Health and Welfare, Helsinki, Finland
| | - Jari Haukka
- Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Valle A, Narain S, Barilla-Labarca ML, Marder G. The differential role of SSa/SSb and Ro52 antibodies in defining clinical phenotypes in idiopathic inflammatory myopathies. Semin Arthritis Rheum 2024; 65:152407. [PMID: 38377624 DOI: 10.1016/j.semarthrit.2024.152407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 01/04/2024] [Accepted: 01/26/2024] [Indexed: 02/22/2024]
Abstract
OBJECTIVE In idiopathic inflammatory myopathies, anti-SSa/SSb and anti-Ro52 are associated with interstitial lung disease (ILD), yet few studies have compared their prognostic utility. Our study analyzes clinical phenotypes associated with anti-SSa/SSb and anti-Ro52 positivity in IIM and their association with ILD. METHODS We performed a retrospective analysis of IIM patients >18-years-old, seen at Northwell Myositis Center 2007- 2018 who met 2017 EULAR/ACR criteria with available anti-SSa/SSb data. Patients who were anti-SSa/SSb(-) and anti-Ro52(+) were excluded from anti-SSa/SSb subgroup analysis but included in Ro52 subgroup analysis. Organ manifestations, pulmonary function tests (PFTs) and comorbidities were recorded. Statistical analyses included Chi-square, Fisher's Exact, Wilcoxon Rank Sum, McNemar's test. RESULTS Of 94 patients included in the final analysis, 35% (33/94) were anti-SSa/SSb positive (+). Of 60 patients with anti-Ro52 data, 42% (25/60) were (+). ILD was more common in anti-SSa/SSb (+) versus anti-SSa/SSb negative patients and anti-Ro52(+) versus anti-Ro52 negative patients (58% vs 25%; p = 0.003 and 64% vs.26%; p = 0,004 respectively). Anti-SSa/SSb (+) was not associated with increased ILD severity based on PFTs. Anti-Ro52(+) group had lower DLCO than anti-Ro52(-) (47% vs 68%; p = 0.003). Anti-SSa/SSb positivity did not confer a difference in the frequency of other manifestations. Elevated rates of venous thromboembolism (VTE) (10%-12%) and osteoporosis (13-17%) were observed independent of anti-SSa/SSb or anti-Ro52 status. CONCLUSION In IIM anti-SSa/SSb or anti-Ro52 positivity is associated with higher ILD rate. Both assays are useful to confer ILD risk, but anti-Ro52 is more predictive of severe ILD. High frequencies of osteoporosis and VTE were observed in all subgroups.
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Affiliation(s)
- Ana Valle
- Division of Rheumatology, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, United States; Department of Internal Medicine, Montefiore Medical Center, Bronx, NY, United States
| | - Sonali Narain
- Division of Rheumatology, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, United States.
| | - Maria-Louise Barilla-Labarca
- Division of Rheumatology, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, United States
| | - Galina Marder
- Division of Rheumatology, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, United States
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Cho EB, Min JH, Waters P, Jeon M, Ju ES, Kim HJ, Kim SH, Shin HY, Kang SY, Lim YM, Oh SY, Lee HL, Sohn E, Lee SS, Oh J, Kim S, Huh SY, Cho JY, Seok JM, Kim BJ, Kim BJ. Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder. Front Immunol 2024; 15:1320094. [PMID: 38576611 PMCID: PMC10991751 DOI: 10.3389/fimmu.2024.1320094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 03/05/2024] [Indexed: 04/06/2024] Open
Abstract
Background Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.
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Affiliation(s)
- Eun Bin Cho
- Department of Neurology, Gyeongsang Institute of Health Science, Gyeongsang National University, College of Medicine, Jinju, Republic of Korea
- Department of Neurology, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Ju-Hong Min
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Neurology, Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
| | - Patrick Waters
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Miyoung Jeon
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Samsung Research Institute of Future Medicine, Seoul, Republic of Korea
| | - Eun-Seon Ju
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Samsung Research Institute of Future Medicine, Seoul, Republic of Korea
| | - Ho Jin Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea
| | - Su-Hyun Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea
| | - Ha Young Shin
- Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sa-Yoon Kang
- Department of Neurology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Young-Min Lim
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sun-Young Oh
- Department of Neurology, Chonbuk National University Hospital, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea
| | - Hye Lim Lee
- Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Eunhee Sohn
- Department of Neurology, Chungnam National University Hospital, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
| | - Sang-Soo Lee
- Department of Neurology, Chungbuk National University Hospital, School of Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Jeeyoung Oh
- Department of Neurology, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Republic of Korea
| | - Sunyoung Kim
- Department of Neurology, Ulsan University Hospital, Ulsan University, College of Medicine, Ulsan, Republic of Korea
| | - So-Young Huh
- Department of Neurology, Kosin University Hospital, College of Medicine, Kosin University, Busan, Republic of Korea
| | - Joong-Yang Cho
- Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Jin Myoung Seok
- Department of Neurology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Byung-Jo Kim
- Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Byoung Joon Kim
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Neurology, Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea
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Einarsdottir MJ, Kibiwott Kirui B, Li H, Olsson D, Johannsson G, Nyberg F, Ragnarsson O. Impact of chronic oral glucocorticoid treatment on mortality in patients with COVID-19: analysis of a population-based cohort. BMJ Open 2024; 14:e080640. [PMID: 38490654 PMCID: PMC10946357 DOI: 10.1136/bmjopen-2023-080640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 03/05/2024] [Indexed: 03/17/2024] Open
Abstract
OBJECTIVES While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes. DESIGN Population-based observational cohort study. SETTINGS Population-based register data in Sweden. PARTICIPANTS All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153). OUTCOME MEASURES Any prior oral GC use was defined as ≥1 GC prescription during 12 months before index. High exposure was defined as ≥2 GC prescriptions with a cumulative prednisolone dose ≥750 mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses. RESULTS 3378 deaths occurred in subjects with any prior GC exposure (n=48 806; 6.9%) and 14 850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction. CONCLUSION Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.
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Affiliation(s)
- Margret J Einarsdottir
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
| | - Brian Kibiwott Kirui
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Huiqi Li
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Daniel Olsson
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
- Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Gudmundur Johannsson
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
| | - Fredrik Nyberg
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
| | - Oskar Ragnarsson
- Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Goteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
- Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
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Yamashita A, Nagae C, Umezawa Y, Mori M, Ashikaga T, Akita M, Suzuki N, Yamazaki S, Takayama S, Taki M. Hemostatic balance between pro- and anticoagulant is maintained during glucocorticoid treatment. Pediatr Blood Cancer 2024; 71:e30812. [PMID: 38078567 DOI: 10.1002/pbc.30812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/27/2023] [Accepted: 11/29/2023] [Indexed: 01/11/2024]
Abstract
BACKGROUND Glucocorticoids are associated with an increased risk of venous thrombosis. Glucocorticoid treatment increases coagulation factor and anticoagulant levels; however, its effect on hemostatic function remains unclear. This study aimed to investigate the changes in comprehensive coagulation profiles after glucocorticoid treatment in noninflammatory diseases to elucidate the direct contribution of glucocorticoids to hemostatic function. PROCEDURE Patients diagnosed with primary immune thrombocytopenia requiring glucocorticoid treatment were prospectively enrolled in this study. Changes in coagulation factors and anticoagulants during glucocorticoid treatment and changes in thrombin generation potential were determined in the absence and presence of soluble thrombomodulin (sTM). RESULTS Seven treatment cases (four for steroid pulse therapy and three for oral glucocorticoid therapy) in six patients with immune thrombocytopenia were examined. After glucocorticoid treatment, activated partial thromboplastin time significantly shortened, and activities of factor VIII, IX, XI, and XII significantly increased, except for von Willebrand factor antigen. Moreover, antithrombin and protein C (PC) activities significantly increased after glucocorticoid treatment. Two major parameters of thrombin generation potential, endogenous thrombin potential (ETP) and peak thrombin (Peak), significantly increased in the absence of sTM after glucocorticoid treatment. However, no significant increases in either parameter were observed in the presence of sTM. ETP-TM and Peak-TM ratios, which represent resistance to the anticoagulant effect of the PC pathway, significantly decreased after glucocorticoid treatment, suggesting that anticoagulant function via the PC pathway is elevated after glucocorticoid treatment. CONCLUSIONS As glucocorticoids increase intrinsic coagulation factor and anticoagulant levels, hemostatic balance between pro- and anticoagulant functions is maintained.
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Affiliation(s)
- Atsuki Yamashita
- Department of Pediatrics, St. Marianna University Yokohama Seibu Hospital, Yokohama, Japan
| | - Chiai Nagae
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Yotaro Umezawa
- Department of Pediatrics, St. Marianna University Yokohama Seibu Hospital, Yokohama, Japan
| | - Mika Mori
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tomoko Ashikaga
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Mieko Akita
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Noriko Suzuki
- Department of Clinical Laboratory, St Marianna University School of Medicine Hospital, Kawasaki, Japan
| | - Satoshi Yamazaki
- Department of Clinical Laboratory, St Marianna University School of Medicine Hospital, Kawasaki, Japan
| | - Shigenobu Takayama
- Faculty of Health Science, Daito Bunka University, Higashimatsuyama, Japan
| | - Masashi Taki
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan
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Fazal ZA, Avina-Galindo AM, Marozoff S, Kwan J, Lu N, Avina-Zubieta JA. Risk of venous thromboembolism in patients with rheumatoid arthritis: a meta-analysis of observational studies. BMC Rheumatol 2024; 8:5. [PMID: 38308337 PMCID: PMC10836002 DOI: 10.1186/s41927-024-00376-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 01/21/2024] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND Thrombotic events, such as venous thromboembolism (VTE) are a major health complication linked to rheumatoid arthritis (RA). We performed a meta-analysis to evaluate the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in adults with RA compared to the general population. METHODS MEDLINE and EMBASE databases were searched from inception to April 2022 to identify publications meeting the following criteria: (1) prospective and retrospective original data from cohort or case-control studies; (2) pre-specified RA definition; (3) clearly defined VTE outcomes; (4) reported risk estimate and 95% confidence intervals (95% CIs); (5) at least sex- and age-matched to comparison group; and (6) English language. Of 372 studies screened, 14 were included (602,760 RA patients, 123,076 VTE events) and their quality was assessed by an adaptation of the STROBE quality scoring scale. RESULTS The pooled risk ratios of VTE, DVT and PE in patients with RA were 1.57 (95% CI 1.41-1.76), 1.58 (95% CI 1.26-1.97) and 1.57 (95% CI 1.30-1.88), respectively. The I2 value of 92%, 94% and 92% for VTE, DVT and PE analyses, suggesting considerable heterogeneity. There were no significant differences in risk estimates among the five subgroup analyses: quality score (P = 0.35, I2 = 0%); sex (P = 0.31, I2 = 1.7%); study year (P = 0.81, I2 = 0%); population source (P = 0.35, I2 = 0%); study design (P = 0.62, I2 = 0%). CONCLUSIONS Results show that patients with RA are at a higher risk of VTE, DVT and PE compared to the general population.
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Affiliation(s)
- Zahra A Fazal
- Arthritis Research Canada, 230-2238 Yukon Street, BC, V5Y 3P2, Vancouver, Canada
- Faculty of Land and Food Systems, University of British Columbia, Vancouver, Canada
| | | | - Shelby Marozoff
- Arthritis Research Canada, 230-2238 Yukon Street, BC, V5Y 3P2, Vancouver, Canada
| | - Jessie Kwan
- Arthritis Research Canada, 230-2238 Yukon Street, BC, V5Y 3P2, Vancouver, Canada
- Faculty of Science, University of British Columbia, Vancouver, Canada
| | - Na Lu
- Arthritis Research Canada, 230-2238 Yukon Street, BC, V5Y 3P2, Vancouver, Canada
| | - J Antonio Avina-Zubieta
- Arthritis Research Canada, 230-2238 Yukon Street, BC, V5Y 3P2, Vancouver, Canada.
- Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada.
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Sammartino F, Dean SM, Baria MR. Superficial Vein Thrombosis After Intra-articular Particulate Steroid Injection for Knee Osteoarthritis. Am J Phys Med Rehabil 2024; 103:e10-e11. [PMID: 37903599 DOI: 10.1097/phm.0000000000002359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2023]
Abstract
ABSTRACT Intra-articular steroid injections for knee osteoarthritis are a routine procedure in musculoskeletal clinics. While their role in osteoarthritis care is debatable, they serve as an important therapeutic option to relieve osteoarthritis-associated pain. Potential risks are self-limited (increased pain flare, local skin irritation, flushing, insomnia) or severe (septic arthritis, intravascular medication placement, and the deleterious effect on cartilage and bone). In our experience, more serious adverse events are rare. In this case, we present a complication secondary to intra-articular steroid administration that has not previously been reported in the literature: superficial vein thrombosis. This will raise awareness among clinicians, improve the informed consent process, and provide an approach for the management of subsequent injections.
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Affiliation(s)
- Francesco Sammartino
- From the Department of Physical Medicine and Rehabilitation, The Ohio State University, Columbus, Ohio (FS, MRB); and Division of Cardiovascular Medicine, The Ohio State University, Davis Heart Lung Institute, Columbus, Ohio (SMD)
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Yang J, Zhou J, Yang J, Lou H, Zhao B, Chi J, Tang W. Dark chocolate intake and cardiovascular diseases: a Mendelian randomization study. Sci Rep 2024; 14:968. [PMID: 38200066 PMCID: PMC10781976 DOI: 10.1038/s41598-023-50351-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Previous intervention studies have shown some benefits of dark chocolate for the cardiovascular system, but it has not been established whether dark chocolate intake is associated with the risk of cardiovascular diseases (CVDs). To investigate the causality between dark chocolate intake and the risk of CVDs, a Mendelian randomization (MR) study was conducted. We obtained summary-level data on dark chocolate intake and CVDs from publicly available genome-wide association studies. In this MR study, the main approach was to use a fixed-effect model with inverse variance weighted (IVW) and evaluate the robustness of the results via sensitivity analysis. We found that dark chocolate intake was significantly associated with the reduction of the risk of essential hypertension (EH) (OR = 0.73; 95% CI 0.60-0.88; p = 1.06 × 10-3), as well as with the suggestive association to the reduced risk of venous thromboembolism (OR = 0.69; 95% CI 0.50-0.96; p = 2.81 × 10-2). However, no association was found between dark chocolate intake and the other ten CVDs. Our study provides evidence for a causality between dark chocolate intake and a reduced risk of EH, which has important implications for the prevention of EH in the population.
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Affiliation(s)
- Juntao Yang
- Department of Cardiology, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, People's Republic of China
| | - Jiedong Zhou
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, People's Republic of China
| | - Jie Yang
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, People's Republic of China
| | - Haifei Lou
- Department of Cardiology, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, People's Republic of China
| | - Bingjie Zhao
- School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, People's Republic of China
| | - Jufang Chi
- Department of Cardiology, Zhuji People's Hospital, Zhuji, 311800, Zhejiang, People's Republic of China
| | - Weiliang Tang
- Department of Cardiology, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, People's Republic of China.
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Yamanaka T, Ishihara T, Hara T, Ichinohe Y, Fukatsu T. Right-sided iliac vein compression syndrome: when the vein is compressed between the internal and external iliac arteries-a case report. Eur Heart J Case Rep 2024; 8:ytae011. [PMID: 38239308 PMCID: PMC10794860 DOI: 10.1093/ehjcr/ytae011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 12/22/2023] [Accepted: 01/03/2024] [Indexed: 01/22/2024]
Abstract
Background In its normal anatomical relationship, the inferior vena cava is located on the right side of the abdominal aorta. Iliac vein compression syndrome (IVCS) is a pathological condition in which a blood clot is formed due to blood flow obstruction when the left common iliac vein is compressed between the right common iliac artery and the vertebral body. Therefore, right-sided IVCS (RIVCS) is rare. The effectiveness of treatment for RIVCS has not been sufficiently investigated. Case summary A 51-year-old man developed deep vein thrombosis in the right lower extremity and non-massive pulmonary embolism during steroid treatment for IgA nephropathy. Magnetic resonance angiography (MRA) suggested iliac compression syndrome. Symptoms improved with the use of direct oral anticoagulants and compression stockings. At the 8-month follow-up, the clinical course was uneventful. Discussion The causes of RIVCS in this case are believed to be the effects of steroids, prolonged sitting, and compression of the right external iliac vein. However, considering that deep vein thrombosis did not form in the left lower limb where there was no venous compression, it can be considered that the compression of the right external iliac vein had a significant impact. This case has been followed up for 8 months with anticoagulants and is progressing well. This is the first case to report the course of RIVCS treated conservatively with anticoagulant therapy for 8 months. This case suggested that conservative treatment is effective for RIVCS.
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Affiliation(s)
- Tetsuo Yamanaka
- Department of Cardiology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo 102-8798, Japan
| | - Tatsuhiko Ishihara
- Department of Cardiology, Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, 6-25-1 Kamiyouga, Setagaya-ku, Tokyo 158-8531, Japan
| | - Toru Hara
- Department of Cardiology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo 102-8798, Japan
| | - Yoshimaro Ichinohe
- Department of Cardiology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo 102-8798, Japan
| | - Toru Fukatsu
- Department of Cardiology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo 102-8798, Japan
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Jin ZY, Li CM, Zheng K, Qu H, Yang WT, Wen JH, Zhang WD, Ren HL. Nomogram for predicting pulmonary embolism in gynecologic inpatients with isolated distal deep venous thrombosis. Int J Gynaecol Obstet 2024; 164:324-333. [PMID: 37597155 DOI: 10.1002/ijgo.15050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/29/2023] [Indexed: 08/21/2023]
Abstract
OBJECTIVE To investigate the incidence of isolated distal deep venous thrombosis (IDDVT) concurrent with pulmonary embolism (PE) in gynecologic inpatients, analyze the risk factors for IDDVT with PE, and establish a nomogram model for IDDVT patients with PE. METHODS A total of 260 patients were diagnosed with IDDVT between December 2017 and November 2020. The incidence of PE in these patients was determined using computed tomography pulmonary angiography. Logistic regression analysis was used to identify the related risk factors. On this basis, nomogram risk prediction models were established. RESULTS Among 260 patients with IDDVT, 106 (40.8%) had concurrent PE, of whom 74 (28.5%) experienced silent PE. Univariate logistic analysis demonstrated statistical significance for body mass index (BMI; P = 0.044), glucocorticoid therapy (P = 0.009), hypertension (P < 0.001), and diabetes (P < 0.001). Multivariate logistic analysis revealed that these were independent risk factors for IDDVT with PE that retained statistical significance. A nomogram based on these factors was constructed to predict PE in patients with IDDVT. Its receiver operating characteristic (ROC) showed an area under the curve of 0.710 (95% confidence interval 0.642-0.779), with prediction sensitivity of 64.2% and prediction specificity of 76.6%. CONCLUSIONS In the present study, a high prevalence of PE was found in gynecologic inpatients with IDDVT. Glucocorticoid therapy, hypertension, diabetes, and BMI were independent risk factors for IDDVT patients with PE. Taking these risk factors into account, a nomogram risk prediction model was developed to help facilitate early detection of concurrent PE.
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Affiliation(s)
- Zhen-Yi Jin
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Chun-Min Li
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Kai Zheng
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hong Qu
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Wen-Tao Yang
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jia-Hao Wen
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Wang-De Zhang
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hua-Liang Ren
- Department of Vascular Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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An AW, Chen X, Urbauer DL, Bruera E, Hui D. Impact of Dosing and Duration of Dexamethasone on Serious Corticosteroid-Related Adverse Events. J Pain Symptom Manage 2024; 67:59-68. [PMID: 37769822 DOI: 10.1016/j.jpainsymman.2023.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/07/2023] [Accepted: 09/14/2023] [Indexed: 10/03/2023]
Abstract
CONTEXT Corticosteroids are commonly prescribed in oncology, but few studies have examined its adverse events (AEs) compared to placebo control. OBJECTIVES Using data from a double-blind, placebo-controlled randomized trial, we evaluated the association between the dose and duration of dexamethasone and serious AEs. METHODS This is a pre-planned secondary analysis of the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial in which patients were randomized to dexamethasone 8 mg BID x1 week, then 4 mg BID x1 week or placebo, followed by an optional open-label phase with 4 mg BID x1 week, then 2 mg BID x1 week. The primary outcome was Grade 3+ AEs (CTCAE v4.03). We evaluated the association between AEs and dexamethasone exposure using multivariable logistic regression. RESULTS Among 119 cancer patients, 32 received intervention followed by open label (mean exposure 243 mg over 27 days), 47 received intervention with no open label, 20 received placebo followed by open label, and 20 received no dexamethasone. The most common AEs included insomnia (31%), dyspepsia (21%), neuropsychiatric symptoms (18%), and infections (17%). Overall, 38 (32%) had Grade 3+ AEs and 27 (23%) were hospitalized. Patients with the greatest exposure to dexamethasone experienced more Grade 3+ AEs compared to those with no exposure (65% vs. 15%); odds ratio of 15.1 (95% CI 1.4-160.8, P = 0.01). CONCLUSION Greater dexamethasone exposure, even at moderate doses, was associated with more serious AEs. Prescribers should cautiously weigh the risks and benefits of dexamethasone use, especially when considering for palliation of symptoms.
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Affiliation(s)
- Amy W An
- Department of Gastrointestinal Medical Oncology (A.W.A.), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
| | - Xi Chen
- Department of Biostatistics (X.C., D.L.U.), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Diana L Urbauer
- Department of Biostatistics (X.C., D.L.U.), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Eduardo Bruera
- Department of Palliative Care (E.B., D.H.), Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - David Hui
- Department of Palliative Care (E.B., D.H.), Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Dhaliwal G, Patrone MV, Bickston SJ. Venous Thromboembolism in Patients with Inflammatory Bowel Disease. J Clin Med 2023; 13:251. [PMID: 38202258 PMCID: PMC10780135 DOI: 10.3390/jcm13010251] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Patients diagnosed with inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, experience chronic inflammation of the gastrointestinal tract. Those with IBD face a higher risk of developing venous thromboembolism (VTE) compared to individuals without IBD. This escalated risk is associated with various factors, some modifiable and others non-modifiable, with disease activity being the primary concern. Interestingly, Janus Kinase inhibitors approved for the treatment of IBD may be associated with an increased risk of VTE but only in patients that have other underlying risk factors leading to an overall increased VTE risk. Several recognized medical societies have recommended the use of VTE prophylaxis for hospitalized individuals with IBD. The association between VTE and IBD and the need for pharmacologic prophylaxis remains under-recognized. Increased awareness of this complication can hopefully protect patients from a potentially deadly complication.
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Affiliation(s)
- Galvin Dhaliwal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA 23219, USA; (M.V.P.); (S.J.B.)
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Papa A, Santini P, De Lucia SS, Maresca R, Porfidia A, Pignatelli P, Gasbarrini A, Violi F, Pola R. Gut dysbiosis-related thrombosis in inflammatory bowel disease: Potential disease mechanisms and emerging therapeutic strategies. Thromb Res 2023; 232:77-88. [PMID: 37951044 DOI: 10.1016/j.thromres.2023.11.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 10/23/2023] [Accepted: 11/03/2023] [Indexed: 11/13/2023]
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and mortality. Chronic inflammation plays a crucial role in the pathogenesis of thrombotic events in patients with IBD. However, many unresolved questions remain, particularly regarding the mechanisms that determine the persistent inflammatory state independent of disease activity. This review explored the role of gut microbiota dysbiosis and intestinal barrier dysfunction, which are considered distinctive features of IBD, in determining pro-thrombotic tendencies. Gut-derived endotoxemia due to the translocation of bacterial lipopolysaccharides (LPS) from the intestine to the bloodstream and the bacterial metabolite trimethylamine-N-oxide (TMAO) are the most important molecules involved in gut dysbiosis-related thrombosis. The pathogenic prothrombotic pathways linked to LPS and TMAO have been discussed. Finally, we present emerging therapeutic approaches that can help reduce LPS-mediated endotoxemia and TMAO, such as restoring intestinal eubiosis, normalizing intestinal barrier function, and counterbalancing the effects of LPS and TMAO.
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Affiliation(s)
- Alfredo Papa
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy.
| | - Paolo Santini
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy; Thrombosis Clinic, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy
| | - Sara Sofia De Lucia
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Rossella Maresca
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Angelo Porfidia
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy; Thrombosis Clinic, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy
| | - Pasquale Pignatelli
- Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro-Napoli, Naples, Italy
| | - Antonio Gasbarrini
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Francesco Violi
- Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro-Napoli, Naples, Italy
| | - Roberto Pola
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Rome, Italy; Thrombosis Clinic, Agostino Gemelli University Polyclinic Foundation IRCCS, Rome, Italy
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Pofi R, Caratti G, Ray DW, Tomlinson JW. Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad? Endocr Rev 2023; 44:975-1011. [PMID: 37253115 PMCID: PMC10638606 DOI: 10.1210/endrev/bnad016] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/25/2023] [Accepted: 05/26/2023] [Indexed: 06/01/2023]
Abstract
It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.
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Affiliation(s)
- Riccardo Pofi
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
| | - Giorgio Caratti
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
| | - David W Ray
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
- NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK
- Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford OX37LE, UK
| | - Jeremy W Tomlinson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
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Taieb D, Pastré J, Juvin K, Bouvry D, Jeny F, Sanchez O, Uzunhan Y, Valeyre D, Nunes H, Israël-Biet D. Prognostic impact of venous thromboembolism on the course of sarcoidosis: A multicenter retrospective case-control study. Respir Med Res 2023; 84:101050. [PMID: 37897877 DOI: 10.1016/j.resmer.2023.101050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 10/30/2023]
Abstract
Sarcoidosis is an independent risk factor for venous thromboembolism (VTE). However, the characteristics and clinical evolution of sarcoidosis patients presenting a VTE (sarcoidosis/VTE group) in the course of their disease are not known. Consequently, if VTE occurrence is associated with a more severe disease is still pending. We conducted a retrospective case-control study of sarcoidosis/VTE patients compared to matched sarcoidosis controls without VTE in two French tertiary centers, analysed and compared the clinical, biological, functional, imaging and evolutive profiles of the two groups. Sixty-one patients were included with at least one episode of VTE during course of sarcoidosis. At sarcoidosis onset (before/at the time of VTE occurrence) the number of affected organs, radiological stages and pulmonary functional tests were not significantly different between the two groups. In contrast, we found that sarcoidosis/VTE patients required more frequently a systemic immunosuppressive therapy (corticosteroids and/or immunosuppressors, 79% versus 58%; p = 0.008). The functional course was also poorer in sarcoidosis/VTE patients with a more frequent decrease in functional vital capacity (33% versus 18% in sarcoidosis/VTE patients and controls, respectively, p = 0.008). Finally, sarcoidosis/VTE patients presented more frequently with pulmonary hypertension (10% versus 1% in patients and controls, respectively, p = 0.006), and their survival was significantly worse (log-rank p <0.001). The occurrence of VTE during sarcoidosis is associated with a more severe disease and a poorer prognosis. The occurrence of VTE during sarcoidosis might signal a more inflammatory and/or evolutive disease in sarcoidosis/VTE patients and should be taken in consideration when designing therapeutic strategies for them.
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Affiliation(s)
- Dov Taieb
- Service de Pneumologie et Soins Intensifs, Assistance Publique-Hôpitaux de Paris Centre, Hôpital Européen Georges Pompidou, 75015 Paris, France; UFR de Médecine, Université Paris Cité, Paris, France.
| | - Jean Pastré
- Service de Pneumologie et Soins Intensifs, Assistance Publique-Hôpitaux de Paris Centre, Hôpital Européen Georges Pompidou, 75015 Paris, France
| | - Karine Juvin
- Service de Pneumologie et Soins Intensifs, Assistance Publique-Hôpitaux de Paris Centre, Hôpital Européen Georges Pompidou, 75015 Paris, France
| | - Diane Bouvry
- Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, 93009 Bobigny, France
| | - Florence Jeny
- Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, 93009 Bobigny, France; INSERM UMR 1272, Université Sorbonne Paris Nord, Bobigny, France
| | - Olivier Sanchez
- Service de Pneumologie et Soins Intensifs, Assistance Publique-Hôpitaux de Paris Centre, Hôpital Européen Georges Pompidou, 75015 Paris, France; UFR de Médecine, Université Paris Cité, Paris, France
| | - Yurdagül Uzunhan
- Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, 93009 Bobigny, France; INSERM UMR 1272, Université Sorbonne Paris Nord, Bobigny, France
| | | | - Hilario Nunes
- Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, 93009 Bobigny, France; INSERM UMR 1272, Université Sorbonne Paris Nord, Bobigny, France
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Liu SH, Cerri-Droz P, Ling K, Loyst RA, Wang KE, Tsouris N, Komatsu DE, Wang ED. Chronic Steroid Use, Complications, and Readmission Following Open Reduction Internal Fixation of Distal Radius Fracture. JOURNAL OF HAND SURGERY GLOBAL ONLINE 2023; 5:757-762. [PMID: 38106944 PMCID: PMC10721537 DOI: 10.1016/j.jhsg.2023.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/15/2023] [Indexed: 12/19/2023] Open
Abstract
Purpose The increasing incidence of both distal radius fractures (DRFs) and chronic conditions that necessitate long-term steroid use has resulted in a growing intersection between the patient populations of the two. Chronic steroid use is known to increase bone frailty and the likelihood of fractures but may also contribute to poorer outcomes following the repair of DRF. The purpose of this study was to investigate the association between preoperative chronic steroid use, postoperative complications, and readmission after open reduction internal fixation (ORIF) of DRF. Methods The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent DRF ORIF between 2015 and 2021. However, 30-day postoperative complications after DRF ORIF were collected. Multivariate logistic regression analysis was conducted to investigate the relationship among preoperative chronic steroid use, postoperative complications, and patient factors associated with readmission. Results The postoperative complications associated with the steroid cohort were categorized as major, minor, and overall complications. Additionally, pneumonia, stroke, myocardial infarction, bleeding transfusions, deep vein thrombosis, pulmonary embolism, readmission, non-home discharge, and mortality were recorded. Chronic steroid use was found to be independently associated with major , minor, and overall complications, deep vein thrombosis, and readmission. Further investigation of readmission showed that male sex and comorbid chronic obstructive pulmonary disease were the only two patient factors independently associated with a greater likelihood of readmission after DRF ORIF. Conclusions Preoperative chronic steroid use was associated with an increasing rate of postoperative complications after DRF ORIF. Male sex and comorbid chronic obstructive pulmonary disease were characteristics of chronic steroid-use patients independently associated with increased risk of readmission after DRF ORIF. A better understanding of preoperative chronic steroid use as a risk factor for postoperative complications may allow surgeons to improve preoperative risk stratification and patient counseling in the management of DRF. Type of study/level of evidence Prognostic III.
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Affiliation(s)
- Steven H. Liu
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | | | - Kenny Ling
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Rachel A. Loyst
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | | | - Nicholas Tsouris
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - David E. Komatsu
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
| | - Edward D. Wang
- Department of Orthopaedics, Stony Brook University, Stony Brook, NY
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Cavalli CAM, Gabbiadini R, Dal Buono A, Quadarella A, De Marco A, Repici A, Bezzio C, Simonetta E, Aliberti S, Armuzzi A. Lung Involvement in Inflammatory Bowel Diseases: Shared Pathways and Unwanted Connections. J Clin Med 2023; 12:6419. [PMID: 37835065 PMCID: PMC10573999 DOI: 10.3390/jcm12196419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/01/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract, frequently associated with extraintestinal manifestations (EIMs) that can severely affect IBD patients' quality of life, sometimes even becoming life-threatening. Respiratory diseases have always been considered a rare and subsequently neglected extraintestinal manifestations of IBD. However, increasing evidence has demonstrated that respiratory involvement is frequent in IBD patients, even in the absence of respiratory symptoms. Airway inflammation is the most common milieu of IBD-related involvement, with bronchiectasis being the most common manifestation. Furthermore, significant differences in prevalence and types of involvement are present between Crohn's disease and ulcerative colitis. The same embryological origin of respiratory and gastrointestinal tissue, in addition to exposure to common antigens and cytokine networks, may all play a potential role in the respiratory involvement. Furthermore, other causes such as drug-related toxicity and infections must always be considered. This article aims at reviewing the current evidence on the association between IBD and respiratory diseases. The purpose is to raise awareness of respiratory manifestation among IBD specialists and emphasize the need for identifying respiratory diseases in early stages to promptly treat these conditions, avoid worsening morbidity, and prevent lung damage.
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Affiliation(s)
- Carolina Aliai Micol Cavalli
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Roberto Gabbiadini
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
| | - Arianna Dal Buono
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
| | - Alessandro Quadarella
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Alessandro De Marco
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
- Division of Gastroenterology and Digestive Endoscopy, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Cristina Bezzio
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Edoardo Simonetta
- Respiratory Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Stefano Aliberti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
- Respiratory Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
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Hung YT, Hung WK, Chi CC. Effects of Preoperative Chronic Steroid Use on Postoperative Outcomes in Orthopedic Surgery: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel) 2023; 16:1328. [PMID: 37765136 PMCID: PMC10536822 DOI: 10.3390/ph16091328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/17/2023] [Accepted: 09/18/2023] [Indexed: 09/29/2023] Open
Abstract
Higher rates of postoperative complications have been found in preoperative chronic steroid users. However, the effects of preoperative chronic steroid use on outcomes in orthopedic surgery were unclear. We performed a systematic review of cohort studies examining the effects of chronic steroid use on postoperative outcomes following orthopedic surgery and searched PubMed, Embase, and CENTRAL through 29 April 2023. We included 17 studies with 1,546,562 patients. No increase in 30-day mortality (adjusted odds ratio (aOR) 1.40, 95% confidence interval (CI) 0.64-3.09) and composite thromboembolic events (aOR 1.61, 95% CI 0.99-2.63) but increases in 30-day overall complications (aOR 1.42, 95% CI 1.16-1.75), wound dehiscence (aOR 2.91, 95% CI 1.49-5.66), infectious complications (any infection (aOR 1.61, 95% CI 1.44-1.80), sepsis (aOR 2.07, 95% CI 1.34-3.21), superficial surgical site infection (SSI) (aOR 1.73, 95% CI 1.03-2.89) and deep SSI (aOR 1.96, 95% CI 1.26-3.05)), re-admission (aOR 1.62, 95% CI 1.48-1.77), both 30-day (aOR 1.28, 95% CI 1.03-1.59) and 1-year re-operation (aOR 1.78, 95% CI 1.09-2.92), pulmonary embolism (aOR 5.94, 95% CI 1.52-23.29), and deep vein thrombosis (aOR 2.07, 95% CI 1.24-3.46) were detected in preoperative steroid users. An increased risk of adverse outcomes following orthopedic surgery in chronic steroid users was found.
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Affiliation(s)
- Yu-Ting Hung
- Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Wei-Kai Hung
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, 5, Fuxing St., Guishan Dist., Taoyuan 33305, Taiwan;
| | - Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, 5, Fuxing St., Guishan Dist., Taoyuan 33305, Taiwan;
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
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