Rheumatoid arthritis elevates cardiovascular disease risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of low-density lipoprotein (LDL) metabolism, increases LDL-receptor breakdown in the liver, which elevates LDL-cholesterol levels. In addition, PCSK9 has direct effects on thrombogenesis and atherosclerotic plaque formation.We aimed to investigate (1) the impact of glucocorticoids and biological disease-modifying antirheumatic drug (bDMARD) treatments on PCSK9 and LDL-cholesterol levels, (2) whether this influence is different when autoantibodies are present and (3) the association between PCSK9 and LDL cholesterol.

In this post hoc analysis of the NORD-STAR trial, 296 newly diagnosed patients starting methotrexate with glucocorticoids, certolizumab pegol, abatacept or tocilizumab were included. Serum PCSK9 and LDL-cholesterol levels were measured at baseline and 24 weeks. Linear regression models were used to analyse the difference in PCSK9 and LDL cholesterol between glucocorticoid and bDMARD treatments at 24 weeks. In the second analysis, the interactions between the treatment groups and autoantibody status were added to the model.

After 24 weeks, PCSK9 levels were higher in the glucocorticoid group than in the combined bDMARD treatment group (-276.0 (95% CI -468.2 to -83.9)). When compared with the bDMARD treatment, these increases were more pronounced in autoantibody-positive patients. Changes in LDL cholesterol exhibited a pattern distinct from PCSK9, as it increased in all treatments.

Glucocorticoid treatment was associated with increased PCSK9 levels after 24 weeks. When compared with the bDMARD treatments, these increases were more pronounced in rheumatoid factor, anticitrullinated protein antibody and antinuclear antibody-positive patients. Our data provide a potential mechanistic link between glucocorticoid treatment and cardiovascular disease.

Inger Bendix Foundation for Medical Research.

EudraCT2011-004720-35, NCT01491815.

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.

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.

Evaluate benefits and harms of prophylactic intraoperative methylprednisolone in subpopulations undergoing infant heart surgery.

Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial, a double-blind randomized placebo-controlled trial.

Twenty-four congenital heart centers.

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).

Methylprednisolone (30 mg/kg) vs. placebo administered into cardiopulmonary bypass pump-priming fluid.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Prognostic and Epidemiologic; Level IV.

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).

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.

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.

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.

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.

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).

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.

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.

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.

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.

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).

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.

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.

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.

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).

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.

ClinicalTrials.gov, NCT05990894.

The widespread use of glucocorticoid (GC) therapy may result in GC-induced adrenal insufficiency (GIAI), but the prevalence and clinical implications remain uncertain.

To ascertain the prevalence and symptoms of GIAI.

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.

Prednisolone treatment a median (IQR) of 13 (10-20) months in duration.

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.

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).

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.

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.

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.

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.

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.

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.

It is unclear how drug-interaction with apixaban influences recurrent venous thromboembolism (VTE) and bleedings in cancer patients.

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.

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.

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.

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.

One-hundred ninety-eight adult cancer patients with a confirmed CVC-associated DVT diagnosis from February 2013 and February 2021 were included.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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).

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.

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.

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.

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).

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/).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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?

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.

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).

In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.

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.

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.

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].

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.