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Horst EA, Mayorga EJ, Baumgard LH. International Symposium on Ruminant Physiology: Integrating our understanding of stress physiology. J Dairy Sci 2025; 108:7675-7695. [PMID: 39947603 DOI: 10.3168/jds.2024-25794] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 11/13/2024] [Indexed: 06/22/2025]
Abstract
Abiotic stressors reduce farm animal productivity, and one of the most globally studied is heat stress (HS) because it compromises almost every profitability metric. Surprisingly, the biological consequences of seemingly very different stressors are highly conserved. Thus, although this review focuses on the broad impact of stress, describing the biology and etiology of how HS alters farm animal productivity provides the conceptual foundation for how all stressors can become pathological. Suboptimal production during HS was traditionally thought to result from hypophagia. However, independent of feed intake, HS affects a plethora of endocrine, physiological, metabolic, circulatory, and immunological variables. It is becoming increasingly clear that these changes are chronologically causal and that the etiological epicenter is a compromised gastrointestinal tract (GIT) barrier. A hyperpermeable GIT allows luminal contents to infiltrate, and these antigens stimulate an immune response with local and systemic inflammatory implications. Once activated, most leukocytes switch from oxidative phosphorylation to aerobic glycolysis and increase their glucose utilization. The glucose requirement of an intensely triggered immune system can exceed 2 kg/d in a lactating dairy cow. Whole-body metabolic adjustments are coordinated to ensure glucose is prioritized for the immune system and this is primarily characterized by increased basal and stimulated circulating insulin, hypercortisolemia, and hyperprolactinemia. This hormonal profile is accompanied by decreased adipose tissue mobilization and skeletal muscle insulin resistance. Interestingly, the aforementioned physiology is almost identical to distinctly different abiotic and biotic stressors. For example, feed restriction, weaning, cold stress, and noise stress all have a similar metabolic and inflammatory footprint, and this physiology can be closely recapitulated by experimentally-induced immune activation. Ultimately, these stressors are "psychological" and emanate their pathology from a compromised GIT barrier. Stress negatively affects GIT epithelia via at least 2 mechanisms: (1) mast cell degranulation and (2) immune cell creation of an apical pro-oxidant environment that paradoxically favors pathogen colonization. The metabolic, physiological, and immunological consequences of stress are highly conserved, and these analogous responses are symmetrical because the GIT is seemingly ground zero for all of them.
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Affiliation(s)
- E A Horst
- Elanco Animal Health, Greenfield, IN 46140
| | - E J Mayorga
- Department of Animal Science, Iowa State University, Ames, IA 50011
| | - L H Baumgard
- Department of Animal Science, Iowa State University, Ames, IA 50011.
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Feng S, Zou R, Wang Y, Huang Y, Zhou Q, Huang Q, Xu H. Stress hyperglycemia ratio as a mortality predictor in non-diabetic septic patients: a retrospective cohort analysis. BMC Infect Dis 2025; 25:752. [PMID: 40414847 DOI: 10.1186/s12879-025-11151-7] [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: 04/12/2025] [Accepted: 05/20/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND The stress hyperglycemia ratio (SHR) is associated with adverse events in critically ill patients. However, the relationship between SHR and mortality in non-diabetic septic patients remains unclear. This study aimed to investigate the correlation between SHR and mortality in non-diabetic septic patients. METHODS This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care (MIMIC-IV) database at Beth Israel Deaconess Medical Center in Boston. The study population was stratified into four groups based on quartiles of the SHR. The primary outcome was in-hospital mortality, while the secondary outcome was ICU mortality. Kaplan-Meier curves, the Log-rank test, and Cox regression analysis were employed to assess the association between SHR and all-cause mortality. Restricted cubic splines (RCS) regression analysis was conducted to explore the nonlinear relationship between SHR and outcomes. Additionally, subgroup analyses were performed to investigate differences among various patient subgroups. RESULTS This study included a cohort of 1,200 patients, with a median age of 68.44 years, and 43.42% were female. The in-hospital mortality and Intensive Care Unit (ICU) mortality rates were 19.67% and 15.42%, respectively. Cox regression analysis revealed that an elevated SHR was independently associated with both in-hospital mortality (Hazard Ratio [HR], 1.50; 95% Confidence Interval [CI], 1.05-2.13; P = 0.02) and ICU mortality (HR, 1.53; 95% CI, 1.04-2.24; P = 0.03). Furthermore, the relationship between SHR and mortality exhibited a U-shaped pattern, indicating that an increase in SHR correlates with an elevated risk of adverse events. The results of subgroup analyses were generally consistent with these findings. CONCLUSIONS In non-diabetic critically ill septic patients, SHR is significantly associated with an increased risk of adverse events. Consequently, SHR emerges as a potential predictor of poor outcomes in non-diabetic septic patients admitted to the ICU.
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Affiliation(s)
- Siyu Feng
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China
| | - Rui Zou
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China
| | - Yue Wang
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China
| | - Yuqin Huang
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China
| | - Quan Zhou
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China
| | - Qiang Huang
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China
| | - Huaqiang Xu
- Department of Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, 441300, China.
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Zhang X, Li Y, Yang Q, Wu S, Song Y, Luo Z, Xu J. Prognostic value of glycemic gap in ST-segment elevation myocardial infarction-associated acute kidney injury. BMC Nephrol 2025; 26:243. [PMID: 40375168 PMCID: PMC12080177 DOI: 10.1186/s12882-025-04167-3] [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: 02/16/2025] [Accepted: 05/08/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND Stress-induced hyperglycemia (SIH) is a common phenomenon in acute myocardial infarction and is associated with poor prognosis. The relationship between glycemic gap (GG), a marker of SIH, and ST-segment elevation myocardial infarction (STEMI)-associated acute kidney injury (STAAKI) remains unclear. This study aims to explore the predictive value of GG for the risk of STAAKI after percutaneous coronary intervention (PCI) in STEMI patients. METHODS This study retrospectively selected patients diagnosed with STEMI who underwent primary PCI. Logistic regression analysis was used to identify the risk factors associated with STAAKI. To examine the dose-response relationship between GG and STAAKI, restricted cubic splines (RCS) were employed. The predictive accuracy of the models was assessed using Delong test, net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS This study included 595 patients, the incidence of STAAKI was 9.2%. Multivariate logistic regression showed LVEF (OR per 1% increase = 0.931, 95% CI: 0.895 ~ 0.969), NT-proBNP (OR per 1 pg/mL increase = 1.579, 95% CI: 1.212 ~ 2.057), and GG (OR per 1 mmol/L increase = 1.379, 95% CI: 1.223 ~ 1.554) as independent predictors of STAAKI. RCS analysis indicated a linear dose-response relationship between GG and STAAKI. After integrating GG, the new model could significantly improve the risk model for STAAKI (Z = 2.77, NRI = 0.780, and IDI = 0.095; All P < 0.05). CONCLUSION GG is an independent risk factor for the occurrence of STAAKI after PCI in STEMI patients, and integrating GG can significantly improve risk modeling regarding STAAKI. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Xiaofu Zhang
- Department of Cardiology, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, China
| | - Yong Li
- Department of Cardiology, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, China
| | - Qinghuan Yang
- Department of Cardiology, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, China
| | - Siwen Wu
- Department of Cardiology, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, China
| | - Yang Song
- Department of Cardiology, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, China
| | - Ziyun Luo
- Department of Nephrology, Yichun People's Hospital, Yichun, Jiangxi, 336000, China.
| | - Jianping Xu
- Department of Cardiology, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, China.
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Dei Cas A, Aldigeri R, Eletto E, Ticinesi A, Nouvenne A, Prati B, Vazzana A, Antonini M, Moretti V, Balestreri E, Spigoni V, Fantuzzi F, Schirò S, Ruffini L, Sverzellati N, Meschi T, Bonadonna R. Hyperglycemia in the diabetic range, but not previous diagnosis of diabetes mellitus, is an independent indicator of poor outcome in patients hospitalized for severe COVID-19. Acta Diabetol 2025:10.1007/s00592-025-02507-1. [PMID: 40314776 DOI: 10.1007/s00592-025-02507-1] [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] [Received: 01/24/2025] [Accepted: 03/29/2025] [Indexed: 05/03/2025]
Abstract
AIMS Diabetes mellitus (DM) and hyperglycemia are associated with poor outcome(s) in COVID-19 hospitalized patients, but their independent impact on prognosis remains unclear. We aimed to assess the impact of DM and hyperglycemia on COVID-19 outcomes. METHODS Clinical data/records from COVID-19 patients admitted to the Parma University-Hospital (February 23rd to March 31st, 2020) were retrieved and analysed (NCT04550403). Fasting plasma glucose (FPG), inflammatory markers and the main biochemical variables were collected at admission. Patients underwent chest high-resolution CT and arterial blood gas analysis to determine the PaO2/FiO2 ratio (P/F ratio). The primary outcome was a composite of intensive care unit admission and/or death. RESULTS Among 756 subjects, 143 (19%) had DM. These patients were older with higher comorbidity rates. The primary outcome occurred in 61.5% DM patients versus 43.4% without DM (p < 0.001). In multivariable analysis (accuracy UC = 0.93), older age, cardiovascular and kidney diseases, FPG ≥ 126 mg/dl, C-reactive protein, and P/F ratio, but not previous DM, were independent risk indicators. CONCLUSIONS DM indicated poor COVID-19 outcomes, but not when adjusted for other clinical variables/comorbities, suggesting that its impact was mostly driven by concomitant factors. The independent role of fasting hyperglycemia points to the need for further research on its contribution to COVID-19.
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Affiliation(s)
- Alessandra Dei Cas
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Raffaella Aldigeri
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Elisa Eletto
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Antonio Nouvenne
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Beatrice Prati
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Angela Vazzana
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Monica Antonini
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Valentina Moretti
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Emanuela Balestreri
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Valentina Spigoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Federica Fantuzzi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Silvia Schirò
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Livia Ruffini
- Nuclear Medicine, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Nicola Sverzellati
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Radiological Sciences, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Riccardo Bonadonna
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy.
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
- Endocrinology, Diabetology and Metabolic Diseases, University of Verona and University Hospital of Verona, Verona, Italy.
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Goswami S, Gist KM, Bjornstad P, Ciccia E, Deep A, Gelbart B, Menon S, Marinari E, Ollberding NJ, Qutob D, Seo J, Soranno DE, Van Wyk B, Starr MC. Hyperglycemia and kidney outcomes in critically ill children and young adults on continuous kidney replacement therapy. Pediatr Nephrol 2025:10.1007/s00467-025-06777-3. [PMID: 40272476 DOI: 10.1007/s00467-025-06777-3] [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] [Received: 10/09/2024] [Revised: 03/27/2025] [Accepted: 03/28/2025] [Indexed: 04/25/2025]
Abstract
BACKGROUND There are limited studies evaluating hyperglycemia in children treated with continuous kidney replacement therapy (CKRT). We evaluated the association of hyperglycemia with kidney outcomes in critically ill children treated with CKRT for acute kidney injury (AKI) or fluid overload. METHODS Secondary analysis of the multicenter retrospective observational Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) study (34 centers, 9 countries). Primary exposure was hyperglycemia on days 0-7 of CKRT (average serum glucose of ≥ 150 mg/dL). Average serum glucose < 150 mg/dL was defined as euglycemic. We stratified the hyperglycemic group with cut-offs ≥ 180 mg/dL, ≥ 200 mg/dL, or ≥ 250 mg/dL. The primary outcome was MAKE-90 (death by 90 days or persistent kidney dysfunction [> 125% baseline serum creatinine, or dialysis dependence]). RESULTS Of 985 participants, 48% (473) had average serum glucose > 150 mg/dL during days 0-7 of CKRT. There were higher rates of death in the hyperglycemic group (44% vs. 32%, p < 0.001) and longer length of stay among survivors (42 vs. 38 days, p = 0.017) compared to the euglycemic group. Those with average glucose ≥ 150 mg/dL had higher unadjusted odds of MAKE-90 (OR: 1.36, 95% CI 1.02-1.81); this finding did not remain after multivariate adjustment. Those with average glucose ≥ 180 mg/dL had higher adjusted odds of MAKE-90 (aOR: 1.44, 95% CI 1.02-2.04). In adjusted analysis, each 10 mg/dL increase in glucose was associated with 3% increased odds of MAKE-90. CONCLUSIONS Hyperglycemia is associated with worse kidney outcomes among young persons on CKRT for AKI or fluid overload. Further studies are needed to evaluate the causality and determine appropriate glucose ranges in this high-risk population.
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Affiliation(s)
- Shrea Goswami
- Division of Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Katja M Gist
- Department of Pediatrics, Colorado Children's Hospital, Aurora, CO, USA
| | - Petter Bjornstad
- Division of Endocrinology, Department of Pediatrics, and Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Eileen Ciccia
- Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO, USA
| | - Akash Deep
- King's College Hospital, London, England
| | - Ben Gelbart
- Royal Children's Hospital, University of Melbourne, Murdoch Children's Research Institute, Melbourne, VIC, Australia
| | - Shina Menon
- Division of Nephrology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
| | | | | | - Dua Qutob
- Sidra Medicine and Weil Cornel Medicine, Doha, Qatar
| | - JangDong Seo
- Department of Pediatrics, Colorado Children's Hospital, Aurora, CO, USA
| | - Danielle E Soranno
- Division of Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
- Weldon School of Bioengineering, Purdue University, West Lafayette, IN, USA
| | - Brynna Van Wyk
- University of Iowa Stead Family Children's Hospital, Carver College of Medicine, Iowa City, IA, USA
| | - Michelle C Starr
- Division of Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
- Division of Child Health Service Research, Department of Pediatrics, Indiana University School of Medicine, 410 W 10 th Street, Suite 2000 A, Indianapolis, IN, 46202, USA.
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Xu H, Lv J, Lin F, Liu L. Combined glycated hemoglobin index and red cell distribution width predict in-hospital mortality in critically ill sepsis patients based on MIMIC-IV analysis. Sci Rep 2025; 15:12266. [PMID: 40210921 PMCID: PMC11986117 DOI: 10.1038/s41598-025-94179-8] [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: 11/10/2024] [Accepted: 03/12/2025] [Indexed: 04/12/2025] Open
Abstract
Red cell distribution width (RDW) and glycated hemoglobin index (HGI) is considered an important tool for assessing the prognosis of sepsis patients, closely related to the risk of mortality associated with sepsis. This study investigates the association between the HGI combined with RDW and the risk of in-hospital mortality in patients with sepsis. We analyzed data from 13,726 sepsis patients who were admitted to the intensive care unit (ICU) for more than 24 h, sourced from the American Medical Information Mart for Intensive Care (MIMIC-IV) database. Kaplan-Meier survival curves and multivariable Cox regression analyses were employed to assess the impact of various variables on patient outcomes, stratified by quartiles of HGI and RDW. Additionally, restricted cubic spline (RCS) analysis was utilized to explore how changes in HGI and RDW might influence the studied outcomes. The results indicated that the highest quartile (Q4) of the combined metrics significantly increased in-hospital mortality compared to the lowest quartile (Q1) (p < 0.0001). Multivariable Cox regression analysis revealed that patients in Q4 faced the highest risk of in-hospital mortality (hazard ratio: 1.22, 95% confidence interval: [1.10-1.36], p < 0.001). RCS analysis demonstrated a nonlinear relationship between HGI-RDW and the risk of adverse outcomes. Further analysis identified significantly elevated risks in patients over 65 years old, those who were widowed, those receiving macrolide antibiotics, and those with congestive heart failure or severe liver disease. In conclusion, elevated levels of the combined HGI and RDW metrics are independent risk factors for adverse outcomes in critically ill patients with sepsis, associated with increased mortality.
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Affiliation(s)
- Huan Xu
- Department of Infectious Diseases, Lishui People's Hospital, The First Affiliated Hospital of Lishui University, No. 1188 Liyang Street, Lishui, 323000, Zhejiang, China
| | - Jiaojian Lv
- Department of Infectious Diseases, Lishui People's Hospital, The First Affiliated Hospital of Lishui University, No. 1188 Liyang Street, Lishui, 323000, Zhejiang, China
| | - Feifei Lin
- Department of Laboratory Medicine, Lishui People'S Hospital, The First Affiliated Hospital of Lishui University, Lishui, 323000, Zhejiang, China
| | - Luxiang Liu
- Department of Infectious Diseases, Lishui People's Hospital, The First Affiliated Hospital of Lishui University, No. 1188 Liyang Street, Lishui, 323000, Zhejiang, China.
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Yeşildal K, Gültop F, Berktaş CK, Akkılıç M, Turgut N. The impact of insulin requirement on mortality and morbidity in non-diabetic covid-19 patients in the intensive care unit: A retrospective, observational study. BMC Anesthesiol 2025; 25:160. [PMID: 40205573 PMCID: PMC11983789 DOI: 10.1186/s12871-025-03037-7] [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: 02/27/2025] [Accepted: 03/28/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND COVID-19 ranges from asymptomatic cases to severe disease with high mortality. Corticosteroids are crucial in treatment, reducing mortality and morbidity. However, the use of corticosteroids poses additional challenges in maintaining glycemic control in COVID-19 patients This study aims to eva-luate the impact of insulin requirement on mortality and morbidity in non-diabetic ICU patients and investigate its correlation with disease severity. METHODS This retrospective cohort study included non-diabetic COVID-19 patients aged ≥ 18 years admitted to the ICU of Prof. Dr. Cemil Taşcıoğlu City Hospital (Turkey) between September 1, 2020, and May 31, 2021. Patients requiring ≥ 24 h of insulin therapy were compared with those who did not need insulin. Data on demographics, severity scores (SOFA, APACHE II, SAPS II), insulin initiation and duration, corticosteroid therapy, mechanical ventilation, antiviral and immunomodulatory treatments, laboratory markers, and infection parameters were analyzed. Mortality and incidence of new-onset diabetes mellitus within the first six months post-discharge were assessed. Statistical analyses were performed using SPSS v22.0, with p < 0.05 considered statistically significant. RESULTS Patients with insulin requirements had higher SOFA (p = 0.001), APACHE II (p < 0.001), and SAPS II (p = 0.041) scores, along with increased mechanical ventilation duration (p < 0.001). While corticosteroid type had no effect, > 1 mg/kg/day methylprednisolone or equivalent dexamethasone significantly increased insulin demand (p = 0.002). Among laboratory markers, only peak CRP levels were significantly higher in insulin-requiring patients (p = 0.001). ICU and total hospital stays were significantly longer in the insulin group (p < 0.001). Although in-hospital mortality was similar, 6-month mortality was significantly higher in insulin-requiring patients (p = 0.022). New-onset DM rates were 4.2% in the non-insulin group vs. 31.1% in the insulin group (p = 0.001). CONCLUSIONS Insulin requirement in non-diabetic COVID-19 ICU patients is a predictor of 6-month mortality. High-dose corticosteroids exacerbate glycemic dysregulation, increasing insulin needs. SARS-CoV-2-induced beta-cell damage and hyperinflammation-related stress hyperglycemia elevate the risk of post-discharge DM. Close monitoring and diabetes screening are essential in this population.
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Affiliation(s)
- Kadir Yeşildal
- Prof. Dr. Cemil Taşcıoğlu City Hospital. Anaestesiology and Reanimation, Ministry of Health, Istanbul, Turkey
| | - Fethi Gültop
- Ankara Etlik City Hospital. Anaestesiology and Reanimation, Ministry of Health, Ankara, Turkey.
| | - Cansu Kılınç Berktaş
- Prof. Dr. Cemil Taşcıoğlu City Hospital. Anaestesiology and Reanimation, Ministry of Health, Istanbul, Turkey
| | - Müslüm Akkılıç
- Prof. Dr. Cemil Taşcıoğlu City Hospital. Anaestesiology and Reanimation, Ministry of Health, Istanbul, Turkey
| | - Namigar Turgut
- Prof. Dr. Cemil Taşcıoğlu City Hospital. Anaestesiology and Reanimation, Ministry of Health, Istanbul, Turkey
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Xia D, Luo X, Zhu Y, Zhu J, Xie Y. Assessment of stress hyperglycemia ratio to predict mortality in critically ill patients with sepsis: a retrospective cohort study from the MIMIC-IV database. Front Endocrinol (Lausanne) 2025; 16:1496696. [PMID: 40225322 PMCID: PMC11985425 DOI: 10.3389/fendo.2025.1496696] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 02/10/2025] [Indexed: 04/15/2025] Open
Abstract
Introduction The stress hyperglycemia ratio (SHR) is a new insulin resistance assessment tool for patients, which has been linked to clinical adverse events. We aimed to explore the SHR-mortality relationship in critically ill patients with sepsis. Methods Patients diagnosed with sepsis, along with blood glucose and hemoglobin A1c levels measured within 24 hours of admission, were retrospectively included in the analysis from the MIMIC-IV database between 2008 to 2019. Patients were stratified into quartile groups (quartile 1 (Q1) to quartile 4 (Q4)) according to SHR level, with 28-day mortality as the primary outcome. The SHR and short term mortality association in patients with sepsis was investigated via Cox regression and Kaplan-Meier analyses. The robustness of the results was verified via multivariate adjustments, multicollinearity, least absolute shrinkage and selection operator (LASSO), and the Boruta algorithm method. The complex relationships among the SHR, short-term mortality were estimated via restricted cubic spline (RCS) analyses. Results 2407 sepsis patients were involved, with a median age of 67 years, and 59.5% were male. Overall, 28-day, 60-day and 90-day mortality were 17.49% (n=421), 21.31% (n=513) and 23.89% (n=575), respectively. After adjusting confounding variables, the SHR was associated with greater short-term mortality, including 28-day (hazard ratio (HR)=1.14, 95% confidence interval (CI)=1.04-1.24, p=0.005; Q4 vs. Q1 (reference group), HR=1.41, 95% CI=1.06-1.87, p=0.017, p_trend=0.005), 60-day (HR=1.12, 95% CI=1.02-1.70, p=0.015; Q4 vs. Q1, HR=1.32, 95% CI=1.02-1.72, p=0.037, p_trend=0.021) and 90-day (HR=1.11, 95% CI=1.02-1.22, p=0.019; Q4 vs. Q1, HR=1.32, 95% CI=1.03-1.68, p=0.027, p_trend=0.017) mortality. Furthermore, the RCS analysis revealed a quasi U-shaped relationship with regards to SHR and short-term mortality in sepsis. The mortality rate increased with a SHR value larger or smaller than 0.9. Conclusions Our research revealed that SHR could serve as a novel indicator for predicting short-term mortality in sepsis patients. SHR demonstrated a quasi U-shaped relationship with short-term mortality in sepsis.
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Affiliation(s)
| | - Xing Luo
- *Correspondence: Xing Luo, ; Youfeng Zhu,
| | - Youfeng Zhu
- Department of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan
University, Guangzhou, Guangdong, China
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Prantner D, Vogel SN. Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α. J Leukoc Biol 2025; 117:qiae215. [PMID: 39360990 DOI: 10.1093/jleuko/qiae215] [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: 08/08/2024] [Accepted: 09/30/2024] [Indexed: 03/30/2025] Open
Abstract
Approximately one million cases of sepsis in the United States occur annually. The early phase of sepsis features dramatic changes in host metabolism and inflammation. While examining the effects of metabolic pathways on inflammation, we discovered that the highly reactive glycolytic metabolite, methylglyoxal (MG), accumulates intracellularly during classical activation of macrophages. Herein, we explored the role of glycolysis and the master regulator of glycolysis, Hypoxia-Inducing Factor-1α (HIF-1α), in inflammation and MG accumulation in mouse and human macrophages. To determine how HIF-1α regulates the inflammatory response of macrophages, we correlated HIF-1α stabilization with proinflammatory gene expression and MG-adduct accumulation in WT vs HIF1a-deficient macrophages treated with LPS or LPS + IFN-γ. A nearly complete loss of HIF-1α protein expression in response to the hypoxia mimetic, cobalt chloride, confirmed the phenotype of the HIF1a-deficient macrophages. Moreover, absence of HIF-1α was also associated with decreased MG accumulation. Increasing the glucose concentration in cultured macrophages was sufficient to cause accumulation of endogenous MG-adducts which correlated with increased Tnf and Il1b expression during classical activation. The use of the MG antagonist, aminoguanidine, led to a significant decrease in Tnf and Il1b expression in both mouse macrophages and the THP-1 human macrophage cell line. Although off-target effects cannot be ruled out, these results are consistent with the possibility that MG regulates cytokine expression in classically activated macrophages. Collectively, this work suggests that HIF-1α stabilization is upstream of MG accumulation and that targeting the activity of HIF-1α in macrophages may be therapeutic during sepsis by limiting endogenous MG accumulation.
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Affiliation(s)
- Daniel Prantner
- Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore St., Suite 380, Baltimore, MD 21201, USA
| | - Stefanie N Vogel
- Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore St., Suite 380, Baltimore, MD 21201, USA
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10
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Xu J, Liang C, Yao S, Wang F. Melatonin Exerts Positive Effects on Sepsis Through Various Beneficial Mechanisms. Drug Des Devel Ther 2025; 19:1333-1345. [PMID: 40026332 PMCID: PMC11871935 DOI: 10.2147/dddt.s509735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 02/12/2025] [Indexed: 03/05/2025] Open
Abstract
In recent years, our understanding of sepsis has greatly advanced. However, due to the complex pathological and physiological mechanisms of sepsis, the mechanisms of sepsis are currently not fully elucidated, and it is difficult to translate the research results into specific sepsis treatment methods. Melatonin possesses broad anti-inflammatory, antioxidant, and immune-regulatory properties, making it a promising therapeutic agent for sepsis. In recent years, further research has deepened our understanding of the potential mechanisms and application prospects of melatonin in sepsis. The mechanisms underlying the protective effects of melatonin in sepsis are multifaceted. In this review, based on a substantial body of clinical trials and animal research findings, we first highlighted the significance of melatonin as an important biomarker for disease progression and prognosis in sepsis. We also described the extensive regulatory mechanisms of melatonin in sepsis-induced organ damage. In addition to its broad anti-inflammatory, and anti-oxidant effects, melatonin exerts positive effects by regulating metabolic disorders, hemodynamics, cell autophagy, cellular ion channels, endothelial cell permeability, ferroptosis and other complex pathological mechanisms. Furthermore, as a safe exogenous supplement with low toxicity, melatonin demonstrates positive synergistic effects with other anti-sepsis agents. In the face of the urgent medical challenge of transforming the increasing knowledge of sepsis molecular mechanisms into therapeutic interventions to improve patient prognosis, melatonin seems to be a promising option.
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Affiliation(s)
- Jing Xu
- Department of Critical Care Medicine, Capital Medical University Electric Power Teaching Hospital/State Grid Beijing Electric Power Hospital, Beijing, People’s Republic of China
| | - Cui Liang
- Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Shanglong Yao
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Fuquan Wang
- Department of Pain Management, China-Japan Friendship Hospital, Beijing, People’s Republic of China
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11
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Christa M, Dennis F, Philip R, Jakob L, Timo S. Admission glucose, HbA1c levels and inflammatory cytokines in patients with acute ST-elevation myocardial infarction. Clin Proteomics 2025; 22:8. [PMID: 39962379 PMCID: PMC11834255 DOI: 10.1186/s12014-025-09530-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 02/04/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND To investigate the association between admission glucose and HbA1c values and inflammatory plasma proteins in hospitalized patients with acute ST-elevation myocardial infarction (STEMI). METHODS This analysis was based on 345 STEMI patients recorded by the population-based Myocardial Infarction Registry Augsburg between 2009 and 2013. Using the OLINK inflammatory panel, a total of 92 protein biomarkers were measured in arterial blood samples, which were obtained within the scope of cardiac catheterization immediately after admission. The associations between admission glucose and HbA1c levels and the 92 protein markers were investigated using multivariable linear regression models. RESULTS Admission glucose showed significantly positive associations with the inflammatory markers IL-10, IL-8, IL-6, FGF-21, IL-7, ST1A1, MCP-1, 4E-BP1, SIRT2, STAMBP and IL-18R1 after Bonferroni adjustment. HbA1c values were only significantly associated with IL-18R1. In stratified analyses, admission glucose was not significantly associated with any plasma protein in the diabetes subgroup, while there were several protein markers that showed significantly positive associations with admission glucose in STEMI patients without known diabetes, namely IL-10, CCL20, IL-8, MCP-1 and IL-6. CONCLUSIONS Admission glucose in patients hospitalized due to an acute STEMI seems to be related to an inflammatory and immune-related response, expressed by an increase in inflammation-related plasma proteins in particular in non-diabetic patients with stress hyperglycemia. The present results may open new avenues for the development of biomarkers suitable as potential diagnostic or prognostic clinical markers.
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Affiliation(s)
- Meisinger Christa
- Epidemiology, Medical Faculty, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany.
| | - Freuer Dennis
- Epidemiology, Medical Faculty, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Raake Philip
- Department of Cardiology, Respiratory Medicine and Intensive Care, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Linseisen Jakob
- Epidemiology, Medical Faculty, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Schmitz Timo
- Epidemiology, Medical Faculty, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
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12
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Mehdi SF, Qureshi MH, Pervaiz S, Kumari K, Saji E, Shah M, Abdullah A, Zahoor K, Qadeer HA, Katari DK, Metz C, Mishra L, LeRoith D, Tracey K, Brownstein MJ, Roth J. Endocrine and metabolic alterations in response to systemic inflammation and sepsis: a review article. Mol Med 2025; 31:16. [PMID: 39838305 PMCID: PMC11752782 DOI: 10.1186/s10020-025-01074-z] [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: 10/17/2024] [Accepted: 01/09/2025] [Indexed: 01/23/2025] Open
Abstract
Severe sepsis is cognate with life threatening multi-organ dysfunction. There is a disturbance in endocrine functions with alterations in several hormonal pathways. It has frequently been linked with dysfunction in the hypothalamic pituitary-adrenal axis (HPA). Increased cortisol or cortisolemia is evident throughout the acute phase, along with changes in the hypothalamic pituitary thyroid (HPT) axis, growth hormone-IGF-1 axis, insulin-glucose axis, leptin, catecholamines, renin angiotensin aldosterone axis, ghrelin, glucagon, hypothalamic pituitary gonadal (HGA) axis, and fibroblast growth factor-21. These changes and metabolic alterations constitute the overall response to infection in sepsis. Further research is essential to look into the hormonal changes that occur during sepsis, not only to understand their potential relevance in therapy but also because they may serve as prognostic indicators.
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Affiliation(s)
- Syed Faizan Mehdi
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | | | - Salman Pervaiz
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Karishma Kumari
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Edwin Saji
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Mahnoor Shah
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Ahmad Abdullah
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Kamran Zahoor
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Hafiza Amna Qadeer
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Disha Kumari Katari
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Christine Metz
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Lopa Mishra
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | - Derek LeRoith
- Division of Endocrinology, Diabetes & Bone Disease, Icahn School of Medicine at Mt. Sinai, New York, NY, USA
| | - Kevin Tracey
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA
| | | | - Jesse Roth
- The Feinstein Institutes for Medical Research/Northwell Health, Manhasset, NY, USA.
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13
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Li XH, Yang XL, Dong BB, Liu Q. Predicting 28-day all-cause mortality in patients admitted to intensive care units with pre-existing chronic heart failure using the stress hyperglycemia ratio: a machine learning-driven retrospective cohort analysis. Cardiovasc Diabetol 2025; 24:10. [PMID: 39780223 PMCID: PMC11714879 DOI: 10.1186/s12933-025-02577-z] [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: 11/07/2024] [Accepted: 01/03/2025] [Indexed: 01/11/2025] Open
Abstract
Chronic heart failure (CHF) poses a significant threat to human health. The stress hyperglycemia ratio (SHR) is a novel metric for accurately assessing stress hyperglycemia, which has been correlated with adverse outcomes in various major diseases. However, it remains unclear whether SHR is associated with 28-day mortality in patients with pre-existing CHF who were admitted to intensive care units (ICUs). This study retrospectively recruited patients who were admitted to ICUs with both acute critical illness and pre-existing CHF from the Medical Information Mart for Intensive Care (MIMIC) database. Characteristics were compared between the survival and non-survival groups. The relationship between SHR and 28-day all-cause mortality was analyzed using restricted cubic splines, receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. The importance of the potential risk factors was assessed using the Boruta algorithm. Prediction models were constructed using machine learning algorithms. A total of 913 patients were enrolled. The risk of 28-day mortality increased with higher SHR levels (P < 0.001). SHR was independently associated with 28-day all-cause mortality, with an unadjusted hazard ratio (HR) of 1.45 (P < 0.001) and an adjusted HR of 1.43 (P < 0.001). Subgroup analysis found that none of the potential risk factors, such as demographics, comorbidities, and drugs, affected the relationship (P for interaction > 0.05). The area under the ROC (AUC) curve for SHR was larger than those for admission blood glucose and HbA1c; the cut-off for SHR was 0.57. Patients with SHR higher than the cut-off had a significantly lower 28-day survival probability (P < 0.001). SHR was identified as one of the key factors for 28-day mortality by the Boruta algorithm. The predictive performance was verified through four machine learning algorithms, with the neural network algorithm being the best (AUC 0.801). For patients with both acute critical illness and pre-existing CHF, SHR was an independent predictor of 28-day all-cause mortality. Its prognostic performance surpasses those of HbA1c and blood glucose, and prognostic models based on SHR provide clinicians with an effective tool to make therapeutic decisions.
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Affiliation(s)
- Xiao-Han Li
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No.1st, Jian She Eastern Road, Zhengzhou, 450052, Henan Province, People's Republic of China
- Faculty of Medicine, Khon Kaen University, No 123, Mittraphap Road, Khon Kaen, 40002, Thailand
| | - Xing-Long Yang
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No.1st, Jian She Eastern Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Bin-Bin Dong
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No.1st, Jian She Eastern Road, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Qi Liu
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No.1st, Jian She Eastern Road, Zhengzhou, 450052, Henan Province, People's Republic of China.
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14
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Defante MLR, Mendes BX, de Souza MDM, De Hollanda Morais BADA, Martins OC, Prizão VM, Parolin SAEC. Tight Versus Liberal Blood Glucose Control in Patients With Diabetes in the ICU: A Meta-Analysis of Randomized Controlled Trials. J Intensive Care Med 2024; 39:1250-1255. [PMID: 38751353 DOI: 10.1177/08850666241255671] [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: 06/06/2024]
Abstract
Introduction: Glycemia is an important factor among critically ill patients in the intensive care unit (ICU). There is conflicting evidence on the preferred strategy of blood glucose control among patients with diabetes in the ICU. We aimed to conduct a meta-analysis comparing tight with liberal blood glucose in critically ill patients with diabetes in the ICU. Methods: We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing tight versus liberal blood glucose control in critically ill patients with diabetes from inception to December 2023. We pooled odds-ratios (OR) and 95% confidence intervals (CI) with a random-effects model for binary endpoints. We used the Review Manager 5.17 and R version 4.3.2 for statistical analyses. Risk of bias assessment was performed with the Cochrane tool for randomized trials (RoB2). Results: Eight RCTs with 4474 patients were included. There was no statistically significant difference in all-cause mortality (OR 1.11; 95% CI 0.95-1.28; P = .18; I² = 0%) between a tight and liberal blood glucose control. RoB2 identified all studies at low risk of bias and funnel plot suggested no evidence of publication bias. Conclusion: In patients with diabetes in the ICU, there was no statistically significant difference in all-cause mortality between a tight and liberal blood glucose control. PROSPERO registration: CRD42023485032.
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Affiliation(s)
- Maria L R Defante
- Department of Medicine, Redentor University Center, Itaperuna, Brazil
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15
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Qi L, Geng X, Feng R, Wu S, Fu T, Li N, Ji H, Cheng R, Wu H, Wu D, Huang L, Long Q, Wang X. Association of glycemic variability and prognosis in patients with traumatic brain injury: A retrospective study from the MIMIC-IV database. Diabetes Res Clin Pract 2024; 217:111869. [PMID: 39332533 DOI: 10.1016/j.diabres.2024.111869] [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: 04/10/2024] [Revised: 07/28/2024] [Accepted: 09/24/2024] [Indexed: 09/29/2024]
Abstract
BACKGROUND Elevated glycemic variability (GV) often occurs in intensive care unit (ICU) patients and is associated with patient prognosis. However, the association between GV and prognosis in ICU patients with traumatic brain injury (TBI) remains unclear. METHOD Clinical data of ICU patients with TBI were obtained from the Medical Information Mart for Intensive Care (MIMIC) -IV database. The coefficient of variation (CV) was utilized to quantify GV, while the Glasgow Coma Scale (GCS) was employed to evaluate the consciousness status of TBI patients. Pearson linear correlation analysis, linear regression, COX regression and restricted cubic spline (RCS) were used to investigate the relationship between CV and consciousness impairment, as well as the risk of in-hospital mortality. RESULT A total of 1641 ICU patients with TBI were included in the study from the MIMIC-IV database. Pearson linear correlation and restricted cubic spline (RCS) analysis results showed a negative linear relationship between CV and the last GCS (P = 0.002) with no evidence of nonlinearity (P for nonlinear = 0.733). Multivariable linear regression suggested a higher CV was associated with a lower discharge GCS [β (95 %CI) = -1.86 (-3.08 ∼ -0.65), P = 0.003]. Furthermore, multivariable COX regression indicated that CV ≥ 0.3 was a risk factor for in-hospital death in TBI patients [HR (95 %CI) = 1.74 (1.15-2.62), P = 0.003], and this result was also consistent across sensitivity and subgroup analyses. CONCLUSION Higher GV is related to poorer consciousness outcomes and increased risk of in-hospital death in ICU patients with TBI. Additional research is needed to understand the logical relationship between GV and TBI progression.
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Affiliation(s)
- Linrui Qi
- Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
| | - Xin Geng
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
| | - Rongliang Feng
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Department of Neurosurgery, the First People's Hospital of Zhaoqing City, Zhaoqing 526060, China.
| | - Shuaishuai Wu
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
| | - Tengyue Fu
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
| | - Ning Li
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
| | - Hongming Ji
- Department of Neurosurgery, Shanxi Provincial People's Hospital, Fifth Hospital of Shanxi Medical University, Shanxi Provincial Key Laboratory of Intelligent, Big Data and Digital Neurosurgery, Shanxi Provincial Key Laboratory of Intelligent Brain Tumor, Taiyuan 030012, China.
| | - Rui Cheng
- Department of Neurosurgery, Shanxi Provincial People's Hospital, Fifth Hospital of Shanxi Medical University, Shanxi Provincial Key Laboratory of Intelligent, Big Data and Digital Neurosurgery, Shanxi Provincial Key Laboratory of Intelligent Brain Tumor, Taiyuan 030012, China.
| | - Hao Wu
- Department of Neurosurgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China.
| | - Dan Wu
- Department of Neurosurgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China.
| | - Lian Huang
- Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
| | - Qingshan Long
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Department of Neurosurgery, Zhongshan Torch Development Zone People's Hospital, Zhongshan 528400, China.
| | - Xiangyu Wang
- Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
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16
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Ma C, Jiang W, Li J, Sun W, Zhang J, Xu P, Guo Y, Ning N, Li J, Zhao B, Mao E, Gao C. Association of Stress Hyperglycemia Ratio and in-Hospital Mortality in Patients with Sepsis: A Two Center Retrospective Cohort Study. J Inflamm Res 2024; 17:7939-7950. [PMID: 39494208 PMCID: PMC11531714 DOI: 10.2147/jir.s476898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 10/18/2024] [Indexed: 11/05/2024] Open
Abstract
INTRODUCTION In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels. METHODS Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients. RESULTS A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile. DISCUSSION In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.
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Affiliation(s)
- Chaoping Ma
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Weisong Jiang
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Juan Li
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Wenwu Sun
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Jiyuan Zhang
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Peixian Xu
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Yiran Guo
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Ning Ning
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Jiaoyan Li
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Bing Zhao
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Enqiang Mao
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Chengjin Gao
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
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Zhang S, Gao L, Li S, Luo M, Xi Q, Lin P, Zhao Z, Zhao Q, Yang T, Zeng Q, Huang Z, Li X, Duan A, Wang Y, Luo Q, Guo Y, Liu Z. Is pulmonary vascular remodeling an intermediate link between hyperglycemia and adverse outcomes in patients with idiopathic pulmonary arterial hypertension? Insights from a multi-center cohort study. Cardiovasc Diabetol 2024; 23:384. [PMID: 39468502 PMCID: PMC11520901 DOI: 10.1186/s12933-024-02476-9] [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: 08/24/2024] [Accepted: 10/16/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Hyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS This multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] - 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes. RESULTS During a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P < 0.001) and ABG (HR 1.317, 95% CI: 1.134, 1.529 per 1.0-unit increment, P < 0.001) were independent predictors of primary endpoint events. Mediation analysis indicated that pulmonary vascular resistance mediated 5.65% and 14.62% of the associations between SHR and ABG and clinical worsening events, respectively. The addition of SHR significantly improved reclassification, discrimination ability, and model fit beyond the clinical risk prediction model. CONCLUSIONS SHR is positively associated with clinical worsening in patients with IPAH. The association appeared to be partially mediated through the pathway of pulmonary vascular remodeling, indicating that SHR may serve as a valuable indicator for providing additional risk information.
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Affiliation(s)
- Sicheng Zhang
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Luyang Gao
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Sicong Li
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Manqing Luo
- Department of Cardiology, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, No. 134, East Street, Gulou District, Fuzhou, 350001, Fujian, China
| | - Qunying Xi
- Center for Pulmonary Vascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Ping Lin
- Department of Pulmonary and Critical Care Medicine, The 900Th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, China
| | - Zhihui Zhao
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Qing Zhao
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Tao Yang
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Qixian Zeng
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Zhihua Huang
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Xin Li
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Anqi Duan
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Yijia Wang
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Qin Luo
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China.
| | - Yansong Guo
- Department of Cardiology, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, No. 134, East Street, Gulou District, Fuzhou, 350001, Fujian, China.
| | - Zhihong Liu
- Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China.
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Li L, Zhou L, Peng X, Zhang Z, Zhang Z, Xiong Y, Hu Z, Yao Y. Association of stress hyperglycemia ratio and mortality in patients with sepsis: results from 13,199 patients. Infection 2024; 52:1973-1982. [PMID: 38679664 DOI: 10.1007/s15010-024-02264-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 04/08/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND The stress hyperglycemia ratio (SHR), adjusted for average glycemic status, is suggested for assessing actual blood glucose levels. Its link with adverse outcomes is known in certain populations, yet its impact on sepsis patients' prognosis is unclear. This study explores the association between SHR and mortality in sepsis. METHODS We included 13,199 sepsis patients in this study and categorized SHR into distinct groups. Additionally, we utilized restricted cubic spline analysis to evaluate the correlation between SHR as a continuous variable and mortality. The primary outcome was 1-year all-cause mortality. Logistic regression and Cox proportional hazards models were employed to assess the associations between the SHR and both in-hospital mortality and 1-year mortality, respectively. RESULTS Among the study participants, 4,690 (35.5%) patients died during the 1-year follow-up. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and 1-year mortality. Using an SHR of 0.99 as the reference point, the hazard ratio for predicted 1-year mortality increased by 1.17 (95% CI 1.08 to 1.27) per standard deviation above 0.99, whereas each standard deviation increase predicted the hazard ratio of 0.52 (95% CI 0.39 to 0.69) below 0.99. Furthermore, we found that SHR could enhance the predictive performance of conventional severity scores. CONCLUSION There exists a U shaped association between SHR and mortality in sepsis patients, where both low and high SHR values are associated with an increased risk of poor outcomes.
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Affiliation(s)
- Le Li
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Likun Zhou
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Xi Peng
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Zhuxin Zhang
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Zhenhao Zhang
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Yulong Xiong
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Zhao Hu
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China
| | - Yan Yao
- Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Peking Union Medical College, Fuwai Hospital, Beijing, 100037, China.
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Ning YL, Xu XH, Niu XL, Zhang Y, Zhou JH, Sun C. The triglyceride-glucose index dynamic trajectory reveals the association between the clinical subphenotype of insulin resistance and mortality in patients with sepsis. BMC Infect Dis 2024; 24:1083. [PMID: 39354398 PMCID: PMC11443761 DOI: 10.1186/s12879-024-10005-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: 08/01/2024] [Accepted: 09/26/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. METHODS In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. RESULTS A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00-1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. CONCLUSION Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients.
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Affiliation(s)
- Yi-Le Ning
- Department of Pulmonary and Critical Care Medicine (PCCM), Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
- The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiang-Hui Xu
- The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Critical Care Medicine, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiao-Li Niu
- Department of Pulmonary and Critical Care Medicine (PCCM), Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yu Zhang
- Department of Critical Care Medicine, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
| | - Ji-Hong Zhou
- Department of Pulmonary and Critical Care Medicine (PCCM), Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
| | - Ce Sun
- The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China.
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20
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Ghosh I, Sangha S, Pandey G, Srivastava A. Efficacy of Polymyxin B Hemoperfusion for Treatment of Sepsis. Indian J Crit Care Med 2024; 28:930-934. [PMID: 39411305 PMCID: PMC11471987 DOI: 10.5005/jp-journals-10071-24805] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 08/20/2024] [Indexed: 10/19/2024] Open
Abstract
Objectives To study the efficacy of polymyxin B hemoperfusion in addition to standard care for sepsis treatment. Materials and methods Fifty sepsis patients (mean age 54.26 ± 14.64 years; 68% males) were randomized to either the case group (n = 25; receiving Polymyxin B hemoperfusion in addition to standard ICU care) or the control group (n = 25; receiving standard ICU care only). The patients were followed up at frequent intervals of 6, 12, 24, 48, and 72 hours. A last follow-up on day 7 was done. The duration of the ICU stay and survival until day 7 were recorded. Changes in clinical and biochemical parameters were also noted and compared. Results Mean sequential organ failure assessment (SOFA) scores at admission were 3.44 ± 1.00 and 2.80 ± 0.82, respectively, in cases and controls. Cases as compared to controls showed faster, and sustainable improvement. No significant difference between the two groups was seen for mortality at day 7. Conclusion Polymyxin B hemoperfusion tends to show a faster recovery and a non-significant trend towards reduced mortality in ICU-admitted sepsis patients. How to cite this article Ghosh I, Sangha S, Pandey G, Srivastava A. Efficacy of Polymyxin B Hemoperfusion for Treatment of Sepsis. Indian J Crit Care Med 2024;28(10):930-934.
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Affiliation(s)
- Indranil Ghosh
- Department of Medicine and Nephrology, Army Hospital (R&R), New Delhi, India
| | - Sukhwinder Sangha
- Department of Medicine and Nephrology, Command Hospital (WC), Chandimandir, Panchkula, Haryana, India
| | - Gaurav Pandey
- Medical Specialist, Sector Hospital, ITBP, Leh, Ladakh, India
| | - Atul Srivastava
- Department of Nephrology, Medicine and Nephrology, Command Hospital (SC), Pune, India
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Agarwal K, Kirti R, Shyama S, Kumar P, Biswas R, Ojha VS. Long-term outcome of patients with diabetic-range hyperglycemia first detected during admission for COVID-19: A single-center observational study. J Family Med Prim Care 2024; 13:3374-3380. [PMID: 39228533 PMCID: PMC11368375 DOI: 10.4103/jfmpc.jfmpc_140_24] [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: 01/27/2024] [Revised: 04/26/2024] [Accepted: 04/27/2024] [Indexed: 09/05/2024] Open
Abstract
Background and Objective Diabetic-range hyperglycemia has been reported for the first time in many patients during their hospitalization with coronavirus disease 2019 (COVID-19). This study was undertaken to determine the proportion of such patients who actually have new-onset diabetes mellitus rather than transient hyperglycemia during acute illness. Methods This descriptive study included patients with diabetic-range hyperglycemia first detected at or during admission for COVID-19 but no prior history of diabetes. The study protocol involved patient identification, data recording from the case-notes, and telephonic follow-ups. Blood sugar levels done at least two weeks after discharge or the last dose of steroids, whichever was later, were recorded, and patients were categorized as diabetic, pre-diabetic, or non-diabetic accordingly. Results Out of 86 patients, ten (11.6%) were found to have developed diabetes, and 13 (15.1%) had pre-diabetes on follow-up. About 63 (73.3%) patients had become normoglycemic. Eight (80%) out of the ten patients with new-onset diabetes were on treatment, with five (50%) achieving the target glycemic levels. The associations of new-onset diabetes with age, gender, comorbidities, intensive care stay, and steroid administration were not found to be statistically significant (p-values 0.809, 0.435, 0.324, 0.402, and 0.289, respectively). Interpretation and Conclusions While a majority of post-COVID patients with diabetic-range hyperglycemia returned to a normoglycemic state after the acute illness had settled down, one in ten developed new-onset diabetes, and an additional one in seven had impaired glucose tolerance. Thus, regular glucose screening is crucial for such patients and lifestyle modifications should be encouraged to reduce the risk of diabetes. Loss to follow-up and reliance on a single set of blood sugar readings for classification were some of the limitations of this study.
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Affiliation(s)
- Ketan Agarwal
- Department of General Medicine, All India Institute of Medical Sciences Patna, Phulwari Sharif, Patna, Bihar, India
| | - Ravi Kirti
- Department of General Medicine, All India Institute of Medical Sciences Patna, Phulwari Sharif, Patna, Bihar, India
| | - Shyama Shyama
- Department of General Medicine, All India Institute of Medical Sciences Patna, Phulwari Sharif, Patna, Bihar, India
| | - Pragya Kumar
- Department of Community and Family Medicine, All India Institute of Medical Sciences Patna, Phulwari Sharif, Patna, Bihar, India
| | - Ratnadeep Biswas
- Department of General Medicine, All India Institute of Medical Sciences Patna, Phulwari Sharif, Patna, Bihar, India
| | - Vishnu S. Ojha
- Department of General Medicine, All India Institute of Medical Sciences Patna, Phulwari Sharif, Patna, Bihar, India
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Hu J, Yang H, Yu M, Yu C, Qiu J, Xie G, Sheng G, Kuang M, Zou Y. Admission blood glucose and 30-day mortality in patients with acute decompensated heart failure: prognostic significance in individuals with and without diabetes. Front Endocrinol (Lausanne) 2024; 15:1403452. [PMID: 39036046 PMCID: PMC11257984 DOI: 10.3389/fendo.2024.1403452] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 06/24/2024] [Indexed: 07/23/2024] Open
Abstract
Objective Diabetes is a significant risk factor for acute heart failure, associated with an increased risk of mortality. This study aims to analyze the prognostic significance of admission blood glucose (ABG) on 30-day mortality in Chinese patients with acute decompensated heart failure (ADHF), with or without diabetes. Methods This retrospective study included 1,462 participants from the JX-ADHF1 cohort established between January 2019 to December 2022. We conducted multivariate cox regression, restricted cubic spline, receiver operating characteristic curve analysis, and mediation analysis to explore the association and potential mechanistic pathways (inflammation, oxidative stress, and nutrition) between ABG and 30-day mortality in ADHF patients, with and without diabetes. Results During the 30-day follow-up, we recorded 20 (5.36%) deaths in diabetic subjects and 33 (3.03%) in non-diabetics. Multivariate Cox regression revealed that ABG was independently associated with 30-day mortality in ADHF patients, with a stronger association in diabetics than non-diabetics (hazard ratio: Model 1: 1.71 vs 1.16; Model 2: 1.26 vs 1.19; Model 3: 1.65 vs 1.37; Model 4: 1.76 vs 1.33). Further restricted cubic spline analysis indicated a U-shaped relationship between ABG and 30-day mortality in non-diabetic ADHF patients (P for non-linearity < 0.001), with the lowest risk at ABG levels approximately between 5-7 mmol/L. Additionally, receiver operating characteristic analysis demonstrated that ABG had a higher predictive accuracy for 30-day mortality in diabetics (area under curve = 0.8751), with an optimal threshold of 13.95mmol/L. Finally, mediation analysis indicated a significant role of inflammation in ABG-related 30-day mortality in ADHF, accounting for 11.15% and 8.77% of the effect in diabetics and non-diabetics, respectively (P-value of proportion mediate < 0.05). Conclusion Our study confirms that ABG is a vital indicator for assessing and predicting 30-day mortality risk in ADHF patients with diabetes. For ADHF patients, both with and without diabetes, our evidence suggests that physicians should be alert and closely monitor any changes in patient conditions when ABG exceeds 13.95 mmol/L for those with diabetes and 7.05 mmol/L for those without. Timely adjustments in therapeutic strategies, including endocrine and anti-inflammatory treatments, are advisable.
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Affiliation(s)
- Jing Hu
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Hongyi Yang
- Department of Ultrasound, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Meng Yu
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Changhui Yu
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Jiajun Qiu
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Guobo Xie
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Guotai Sheng
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Maobin Kuang
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Yang Zou
- Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
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Zhang Q, Xiang H, Xu Q, Hu Z, Xue Y, Wang J, Ji K. Stress hyperglycemia ratio linked to worse prognosis in Cardiac Intensive Care Unit patients: A retrospective observational study. Diabetes Res Clin Pract 2024; 209:111598. [PMID: 38431225 DOI: 10.1016/j.diabres.2024.111598] [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: 11/09/2023] [Revised: 02/17/2024] [Accepted: 02/25/2024] [Indexed: 03/05/2024]
Abstract
AIMS This study aimed to delineate correlation between stress hyperglycemia ratio (SHR) and clinical outcomes among patients in the cardiac intensive care unit (CICU). METHODS Participants were categorized based on their SHR threshold values. Key outcomes were short-term mortality and major adverse cardiovascular events (MACEs) at 1-year follow-up. The association between SHR and outcomes was estimated using inverse probability of treatment weighting (IPTW) and Kaplan-Meier analyses. The C-statistic was used to gauge the predictive capability of SHR. RESULTS The study included 1,133 patients from the Medical Information Mart for Intensive Care IV and 412 from the Second Affiliated Hospital of Wenzhou Medical University. Kaplan-Meier curves revealed that individuals with elevated SHR exhibited higher 90-day mortality and MACEs. When considering SHR levels and diabetes status simultaneously, those with increased SHR but non-diabetes had the highest 90-day mortality and MACEs. SHR was associated with short-term mortality and MACEs (HRadjusted 1.63 95%CI 1.15-2.30; HRIPTW 1.47 95%CI 1.05-2.05). Upon integrating SHR into the foundational model, the C-statistic was 0.821, outperforming other hyperglycemia metrics. CONCLUSION SHR is a valuable indicator for predicting poor outcomes in CICU patients. Its utility spans potential risk stratification and offers insights for tailoring prognostic treatments to CICU patients.
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Affiliation(s)
- Qianqian Zhang
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Huaqiang Xiang
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Qianqian Xu
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Zesong Hu
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Yangjing Xue
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Jie Wang
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
| | - Kangting Ji
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
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Bang HJ, Youn CS, Park KN, Oh SH, Kim HJ, Kim SH, Park SH. Glucose control and outcomes in diabetic and nondiabetic patients treated with targeted temperature management after cardiac arrest. PLoS One 2024; 19:e0298632. [PMID: 38330019 PMCID: PMC10852315 DOI: 10.1371/journal.pone.0298632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 01/27/2024] [Indexed: 02/10/2024] Open
Abstract
Hyperglycemia is commonly observed in critically ill patients and postcardiac arrest patients, with higher glucose levels and variability associated with poorer outcomes. In this study, we aim to compare glucose control in diabetic and nondiabetic patients using glycated hemoglobin (HbA1c) levels, providing insights for better glucose management strategies. This retrospective observational study was conducted at Seoul St. Mary's Hospital from February 2009 to May 2022. Blood glucose levels were measured hourly for 48 h after return of spontaneous circulation (ROSC), and a glucose management protocol was followed to maintain arterial blood glucose levels between 140 and 180 mg/dL using short-acting insulin infusion. Patients were categorized into four groups based on diabetes status and glycemic control. The primary outcomes assessed were neurological outcome and mortality at 6 months after cardiac arrest. Among the 332 included patients, 83 (25.0%) had a previous diabetes diagnosis, and 114 (34.3%) had an HbA1c of 6.0% or higher. At least one hyperglycemic episode was observed in 314 patients (94.6%) and hypoglycemia was found in 63 patients (19.0%) during 48 h. After the categorization, unrecognized diabetes was noticed in 51 patients with median HbA1c of 6.3% (interquartile range [IQR] 6.1-6.6). Patients with inadequate diabetes control had the highest initial HbA1c level (7.0%, IQR 6.5-7.8) and admission glucose (314 mg/dL, IQR 257-424). Median time to target glucose in controlled diabetes was significantly shorter with the slowest glucose reducing rate. The total insulin dose required to reach the target glucose level and cumulative insulin requirement during 48 h were different among the categories (p <0.001). Poor neurological outcomes and mortality were more frequently observed in patients with diagnosed diabetes. Occurrence of a hypoglycemic episode during the 48 h after ROSC was independently associated with poor neurologic outcomes (odds ratio [OR] 3.505; 95% confidence interval [CI], 2.382-9.663). Surviving patients following cardiac arrest exhibited variations in glucose hemodynamics and outcomes according to the categories based on their preexisting diabetes status and glycemic condition. Specifically, even experiencing a single episode of hypoglycemia during the acute phase could have an influence on unfavorable neurological outcomes. While the classification did not directly affect neurological outcomes, the present results indicate the need for a customized approach to glucose control based on these categories.
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Affiliation(s)
- Hyo Jin Bang
- Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chun Song Youn
- Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyu Nam Park
- Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Hoon Oh
- Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyo Joon Kim
- Department of Emergency Medicine, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soo Hyun Kim
- Department of Emergency Medicine, Eunpyeong St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Hyun Park
- Department of Emergency Medicine, Yeouido St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Dicle Y, Aydin E, Seker U. Investigation of the protective activity of baicalein on the lungs via regulation of various cellular responses in rats exposed to experimental sepsis. Toxicol Res (Camb) 2024; 13:tfad112. [PMID: 38178997 PMCID: PMC10762668 DOI: 10.1093/toxres/tfad112] [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: 07/10/2023] [Revised: 10/27/2023] [Accepted: 11/20/2023] [Indexed: 01/06/2024] Open
Abstract
Backgrounds In the present study, a cecal ligation and puncture (CLP)-induced experimental sepsis rat model was used to explore the effects of baicalein on inflammatory cytokine levels and oxidative stress as well as the possible regulatory role of nuclear factor-kappa B (NF-κB). Methods For that purpose, 42 Wistar albino rats were equally divided into control, sham, sepsis, B50 + S, B100 + S, S + B50, and S + B100 groups. The B50 + S and B100 + S groups received baicalein before the induction of sepsis, while the S + B50 and S + B100 groups received baicalein afterwards. Experimental sepsis in related groups is generated through ligation of cecum and a puncture in cecal wall. Serum samples were used for tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) analyses, and tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), IL-6, and NF-κB levels were measured. Results Compared to the control group, there were significantly increases in the serum TNF-α, IL-6, tissue MDA, and NF-κB levels and decreases in the tissue SOD and GSH levels in the septic group (P < 0.05). Compared to the septic group, inflammation and oxidative stress were reduced in the baicalein-treated groups. Although all of the pre- and post-treatment protocols alleviated inflammation and oxidative stress to varying degrees, pre-treatment with 100 mg/kg was the most successful. Conclusions Findings of this study indicated that baicalein has the potential to reduce sepsis-related oxidative stress and inflammation in the lungs and that pathological outcomes could be regulated via NF-κB transcription factor activity.
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Affiliation(s)
- Yalcin Dicle
- Department of Medical Microbiology, Faculty of Medicine, Mardin Artuklu University, 47200, Mardin, Türkiye
| | - Elif Aydin
- Tavsanli Vocational School of Health Services, Kutahya Health Sciences University, 43300, Kutahya, Türkiye
| | - Ugur Seker
- Department of Histology and Embryology, Faculty of Medicine, Mardin Artuklu University, 47200, Mardin, Türkiye
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Hryciw BN, Ghossein J, Rochwerg B, Meggison H, Fernando SM, Kyeremanteng K, Tran A, Seely AJE. Glycemic Variability As a Prognostic Factor for Mortality in Patients With Critical Illness: A Systematic Review and Meta-Analysis. Crit Care Explor 2024; 6:e1025. [PMID: 38222872 PMCID: PMC10786590 DOI: 10.1097/cce.0000000000001025] [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] [Indexed: 01/16/2024] Open
Abstract
OBJECTIVES To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness. DATA SOURCES We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023. STUDY SELECTION We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU. DATA EXTRACTION Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty of pooled estimates. DATA SYNTHESIS We included 41 studies (n = 162,259). We demonstrate that increased sd, coefficient of variance, glycemic lability index, and decreased time in range are probably associated with increased mortality in critically ill patients (moderate certainty) and that increased mean absolute glucose, mean amplitude of glycemic excursion, and detrended fluctuation analysis may be associated with increased mortality (low certainty). CONCLUSIONS We found a consistent association between increased measures of glycemic variability and higher short-term mortality in patient with critical illness. Further research should focus on standardized measurements of glycemic variation and complexity, along with their utility as therapeutic targets and prognostic markers.
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Affiliation(s)
- Brett N Hryciw
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Jamie Ghossein
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Bram Rochwerg
- Department of Medicine, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
| | - Hilary Meggison
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Shannon M Fernando
- Department of Critical Care, Lakeridge Health Corporation, Oshawa, ON, Canada
| | - Kwadwo Kyeremanteng
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Alexandre Tran
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Andrew J E Seely
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Division of Thoracic Surgery, Department of Surgery, The Ottawa Hospital, Ottawa, ON, Canada
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada
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Zhang L, Shi X, Qiu H, Liu S, Yang T, Li X, Liu X. Protein modification by short-chain fatty acid metabolites in sepsis: a comprehensive review. Front Immunol 2023; 14:1171834. [PMID: 37869005 PMCID: PMC10587562 DOI: 10.3389/fimmu.2023.1171834] [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: 02/22/2023] [Accepted: 09/15/2023] [Indexed: 10/24/2023] Open
Abstract
Sepsis is a major life-threatening syndrome of organ dysfunction caused by a dysregulated host response due to infection. Dysregulated immunometabolism is fundamental to the onset of sepsis. Particularly, short-chain fatty acids (SCFAs) are gut microbes derived metabolites serving to drive the communication between gut microbes and the immune system, thereby exerting a profound influence on the pathophysiology of sepsis. Protein post-translational modifications (PTMs) have emerged as key players in shaping protein function, offering novel insights into the intricate connections between metabolism and phenotype regulation that characterize sepsis. Accumulating evidence from recent studies suggests that SCFAs can mediate various PTM-dependent mechanisms, modulating protein activity and influencing cellular signaling events in sepsis. This comprehensive review discusses the roles of SCFAs metabolism in sepsis associated inflammatory and immunosuppressive disorders while highlights recent advancements in SCFAs-mediated lysine acylation modifications, such as substrate supplement and enzyme regulation, which may provide new pharmacological targets for the treatment of sepsis.
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Affiliation(s)
- Liang Zhang
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, China
| | - Xinhui Shi
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, China
| | - Hongmei Qiu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, China
| | - Sijia Liu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, China
| | - Ting Yang
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, China
| | - Xiaoli Li
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, China
| | - Xin Liu
- Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing, China
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Tsai YH, Hung KY, Fang WF. Use of Peak Glucose Level and Peak Glycemic Gap in Mortality Risk Stratification in Critically Ill Patients with Sepsis and Prior Diabetes Mellitus of Different Body Mass Indexes. Nutrients 2023; 15:3973. [PMID: 37764757 PMCID: PMC10534504 DOI: 10.3390/nu15183973] [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: 08/24/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Sepsis remains a critical concern in healthcare, and its management is complicated when patients have pre-existing diabetes and varying body mass indexes (BMIs). This retrospective multicenter observational study, encompassing data from 15,884 sepsis patients admitted between 2012 and 2017, investigates the relationship between peak glucose levels and peak glycemic gap in the first 3 days of ICU admission, and their impact on mortality. The study reveals that maintaining peak glucose levels between 141-220 mg/dL is associated with improved survival rates in sepsis patients with diabetes. Conversely, peak glycemic gaps exceeding 146 mg/dL are linked to poorer survival outcomes. Patients with peak glycemic gaps below -73 mg/dL also experience inferior survival rates. In terms of predicting mortality, modified Sequential Organ Failure Assessment-Peak Glycemic Gap (mSOFA-pgg) scores outperform traditional SOFA scores by 6.8% for 90-day mortality in overweight patients. Similarly, the modified SOFA-Peak Glucose (mSOFA-pg) score demonstrates a 17.2% improvement over the SOFA score for predicting 28-day mortality in underweight patients. Importantly, both mSOFA-pg and mSOFA-pgg scores exhibit superior predictive power compared to traditional SOFA scores for patients at high nutritional risk. These findings underscore the importance of glycemic control in sepsis management and highlight the potential utility of the mSOFA-pg and mSOFA-pgg scores in predicting mortality risk, especially in patients with diabetes and varying nutritional statuses.
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Affiliation(s)
- Yi-Hsuan Tsai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.-H.T.); (K.-Y.H.)
| | - Kai-Yin Hung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.-H.T.); (K.-Y.H.)
- Department of Nutritional Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
- Department of Nursing, Mei Ho University, Pingtung 91202, Taiwan
| | - Wen-Feng Fang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.-H.T.); (K.-Y.H.)
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan
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Angelis D, Jaleel MA, Brion LP. Hyperglycemia and prematurity: a narrative review. Pediatr Res 2023; 94:892-903. [PMID: 37120652 DOI: 10.1038/s41390-023-02628-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/11/2023] [Accepted: 04/15/2023] [Indexed: 05/01/2023]
Abstract
Hyperglycemia is commonly encountered in extremely preterm newborns and physiologically can be attributed to immaturity in several biochemical pathways related to glucose metabolism. Although hyperglycemia is associated with a variety of adverse outcomes frequently described in this population, evidence for causality is lacking. Variations in definitions and treatment approaches have further complicated the understanding and implications of hyperglycemia on the immediate and long-term effects in preterm newborns. In this review, we describe the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research. IMPACT: Hyperglycemia is common and less well described than hypoglycemia in extremely preterm newborns. Hyperglycemia can be attributed to immaturity in several cellular pathways involved in glucose metabolism in this age group. Hyperglycemia has been shown to be associated with a variety of adverse outcomes frequently described in this population; however, evidence for causality is lacking. Variations in definitions and treatment approaches have complicated the understanding and the implications of hyperglycemia on the immediate and long-term effects outcomes. This review describes the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research.
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Affiliation(s)
- Dimitrios Angelis
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Mambarambath A Jaleel
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Luc P Brion
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
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30
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Pan LN, Pan SA, Hong GL, Chen KW. A New Nomogram for Predicting 30-Day In-Hospital Mortality Rate of Acute Cholangitis Patients in the Intensive Care Unit. Emerg Med Int 2023; 2023:9961438. [PMID: 37599814 PMCID: PMC10435307 DOI: 10.1155/2023/9961438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 07/19/2023] [Accepted: 07/27/2023] [Indexed: 08/22/2023] Open
Abstract
Purpose Acute cholangitis (AC) is a widespread acute inflammatory disease and the main cause of septic shock, which has a high death rate in hospitals. At present, the prediction models for short-term mortality of AC patients are still not ideal. We aimed at developing a new model that could forecast the short-term mortality rate of AC patients. Methods Data were extracted from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). There were a total of 506 cases of AC patients that were included. Patients were given a 7 : 3 split between the training set and the validation set after being randomly assigned to one of the groups. Multivariate logistic regression was used to create an AC patient predictive nomogram for 30-day mortality. The overall efficacy of the model is evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA). Results Out of 506 patients, 14.0% (71 patients) died. The training cohort had 354 patients, and the validation cohort had 152 patients. GCS, SPO2, albumin, AST/ALT, glucose, potassium, PTT, and peripheral vascular disease were the independent risk factors according to the multivariate analysis results. The newly established nomogram had better prediction performance than other common scoring systems (such as SOFA, OASIS, and SAPS II). For two cohorts, the calibration curve demonstrated coherence between the nomogram and the ideal observation (P > 0.05). The clinical utility of the nomogram in both sets was revealed by decision curve analysis. Conclusion The novel prognostic model was effective in forecasting the 30-day mortality rate for acute cholangitis patients.
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Affiliation(s)
- Li-Na Pan
- Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Shen-Ao Pan
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou 325035, China
| | - Guang-Liang Hong
- Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Kun-Wei Chen
- Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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de Baat A, Trinh B, Ellingsgaard H, Donath MY. Physiological role of cytokines in the regulation of mammalian metabolism. Trends Immunol 2023:S1471-4906(23)00110-2. [PMID: 37423882 DOI: 10.1016/j.it.2023.06.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/09/2023] [Accepted: 06/09/2023] [Indexed: 07/11/2023]
Abstract
The innate cytokine system is involved in the response to excessive food intake. In this review, we highlight recent advances in our understanding of the physiological role of three prominent cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), in mammalian metabolic regulation. This recent research highlights the pleiotropic and context-dependent functions in the immune-metabolic interplay. IL-1β is activated in response to overloaded mitochondrial metabolism, stimulates insulin secretion, and allocates energy to immune cells. IL-6 is released by contracting skeletal muscle and adipose tissue and directs energy from storing tissues to consuming tissues. TNF induces insulin resistance and prevents ketogenesis. Additionally, the therapeutic potential of modulating the activity of each cytokine is discussed.
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Affiliation(s)
- Axel de Baat
- Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland; Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Beckey Trinh
- The Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark
| | - Helga Ellingsgaard
- The Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark
| | - Marc Y Donath
- Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland; Department of Biomedicine, University of Basel, Basel, Switzerland.
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Barbosa M, Marques-Sá J, Carvalho C, Fernandes V. Is elevated blood glucose at admission associated with poor outcomes in hospitalized COVID-19 patients? ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 67:e000649. [PMID: 37364151 PMCID: PMC10661009 DOI: 10.20945/2359-3997000000649] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 02/27/2023] [Indexed: 06/28/2023]
Abstract
Objective Hyperglycemia has been suggested as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19). The aim of our work was to evaluate the association between blood glucose levels at admission (BGA) and disease outcomes in hospitalized COVID-19 patients. Subjects and methods Retrospective study including all adult COVID-19 patients admitted to a Portuguese hospital from March to August 2020 with BGA measurement. Subjects were categorized into two groups: BGA < 140 mg/dL and ≥ 140 mg/dL. Statistical analysis was performed using SPSSv26® (significance defined as p < 0.05). Results We included 202 patients: median age 74 (60-86) years; 43.1% female; 31.2% with diabetes. The median BGA was 130.5 (108-158) mg/dL. When compared to normoglycemic, patients with BGA ≥ 140 mg/dL were older (p = 0.013), more vaccinated for influenza (p = 0.025) and had more comorbidities (hypertension, heart failure and peripheral arterial disease, p < 0.05). The last group presented higher leucocyte and neutrophile count, higher procalcitonin and prothrombin time, and lower lymphocyte count. Concerning prognosis, BGA ≥ 140 mg/dL was associated with higher rates of mechanical ventilation requirement and intensive care unit admission (p < 0.001), shock (p = 0.011), in-hospital mortality (p = 0.022) and 30-day mortality (p = 0.037). Considering only non-diabetic patients (n = 139), those with hyperglycemia presented higher rates of severity indicators (polypnea, SatO2 ≤ 93% and PaO2/FiO2 ≤ 300) and an association with poor outcomes was also found, namely mechanical ventilation requirement and in-hospital/30-day mortality (p < 0.05). Conclusion Hyperglycemia at admission was associated with poor outcomes in COVID-19 patients, even in those without known pre-existing diabetes. Glycemic testing should be recommended for all COVID-19 patients.
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Affiliation(s)
- Mariana Barbosa
- Serviço de Endocrinologia, Hospital de Braga, Braga, Portugal,
| | | | - Carla Carvalho
- Escola de Medicina, Universidade do Minho, Braga, Portugal
| | - Vera Fernandes
- Serviço de Endocrinologia, Hospital de Braga, Braga, Portugal
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Zahedi M, Kordrostami S, Kalantarhormozi M, Bagheri M. A Review of Hyperglycemia in COVID-19. Cureus 2023; 15:e37487. [PMID: 37187644 PMCID: PMC10181889 DOI: 10.7759/cureus.37487] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Diabetes mellitus (DM) is one of the most common chronic metabolic disorders worldwide, which increases the risk of common and opportunistic infections. Following the coronavirus disease 2019 (COVID-19) pandemic, a higher incidence rate, more severe forms of the disease, and exacerbation of hyperglycemia and its complications have been observed in patients with DM. Moreover, stress-induced hyperglycemia has been observed in many hospitalized nondiabetic patients after contracting COVID-19. Hyperglycemia worsens prognosis in both diabetic and nondiabetic patients. In this study, the mechanism of new-onset or exacerbation of hyperglycemia, the effect of the treatments used for COVID-19 on hyperglycemia, the importance and appropriate method of blood glucose (blood sugar (BS)) control during the disease, and the possible fate of new-onset hyperglycemia after recovery from COVID-19 to some extent is expressed.
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Affiliation(s)
- Maryam Zahedi
- Department of Internal Medicine, Endocrinology, and Metabolism, Clinical Research Development Unit (CRDU) 5 Azar Hospital, Golestan University of Medical Sciences, Gorgan, IRN
| | - Saba Kordrostami
- Department of Endocrinology and Diabetes, Clinical Research Development Unit (CRDU) 5 Azar Hospital, Golestan University of Medical Sciences, Gorgan, IRN
| | | | - Marziyeh Bagheri
- Department of Internal Medicine, Bushehr University of Medical Sciences, Bushehr, IRN
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Dumas JA, Bunn JY, LaMantia MA, McIsaac C, Senft Miller A, Nop O, Testo A, Soares BP, Mank MM, Poynter ME, Lawrence Kien C. Alteration of brain function and systemic inflammatory tone in older adults by decreasing the dietary palmitic acid intake. AGING BRAIN 2023; 3:100072. [PMID: 37408793 PMCID: PMC10318304 DOI: 10.1016/j.nbas.2023.100072] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 03/12/2023] Open
Abstract
Prior studies in younger adults showed that reducing the normally high intake of the saturated fatty acid, palmitic acid (PA), in the North American diet by replacing it with the monounsaturated fatty acid, oleic acid (OA), decreased blood concentrations and secretion by peripheral blood mononuclear cells (PBMCs) of interleukin (IL)-1β and IL-6 and changed brain activation in regions of the working memory network. We examined the effects of these fatty acid manipulations in the diet of older adults. Ten subjects, aged 65-75 years, participated in a randomized, cross-over trial comparing 1-week high PA versus low PA/high OA diets. We evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory and a resting state scan, cytokine secretion by lipopolysaccharide (LPS)-stimulated PBMCs, and plasma cytokine concentrations. During the low PA compared to the high PA diet, we observed increased activation for the 2-back minus 0-back conditions in the right dorsolateral prefrontal cortex (Broadman Area (BA) 9; p < 0.005), but the effect of diet on working memory performance was not significant (p = 0.09). We observed increased connectivity between anterior regions of the salience network during the low PA/high OA diet (p < 0.001). The concentrations of IL-1β (p = 0.026), IL-8 (p = 0.013), and IL-6 (p = 0.009) in conditioned media from LPS-stimulated PBMCs were lower during the low PA/high OA diet. This study suggests that lowering the dietary intake of PA down-regulated pro-inflammatory cytokine secretion and altered working memory, task-based activation and resting state functional connectivity in older adults.
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Affiliation(s)
- Julie A. Dumas
- Department of Psychiatry, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Janice Y. Bunn
- Department of Medical Biostatistics, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Michael A. LaMantia
- Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Catherine McIsaac
- Clinical Research Center, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Anna Senft Miller
- Department of Psychiatry, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Olivia Nop
- Department of Psychiatry, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Abigail Testo
- Department of Psychiatry, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Bruno P. Soares
- Department of Radiology, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Madeleine M. Mank
- Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - Matthew E. Poynter
- Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
| | - C. Lawrence Kien
- Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
- Department of Pediatrics, Larner College of Medicine, The University of Vermont, Burlington, VT, USA
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Kastl BC, Springer NL. Serum biochemical changes in cats with naturally acquired feline cytauxzoonosis. J Am Vet Med Assoc 2023; 261:517-525. [PMID: 36656676 DOI: 10.2460/javma.22.05.0207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVE The geographical distribution of feline cytauxzoonosis is expanding in the US. Clinical signs of feline cytauxzoonosis, including lethargy, anorexia, and icterus, are similar to hepatic lipidosis and cholangiohepatitis. Hematologic and serum biochemical abnormality patterns may assist practitioners in prioritizing feline cytauxzoonosis as a differential diagnosis over hepatic lipidosis and cholangiohepatitis. SAMPLE Hematology and serum biochemical profiles of cats with naturally acquired feline cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. PROCEDURES Retrospective search and analysis of the Kansas State Veterinary Diagnostic Laboratory or Kansas State University Veterinary Health Center records between January 2007 and June 2018 for cats with cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. RESULTS Patients with acute feline cytauxzoonosis presented with frequent nonregenerative anemia (20/28 [71%]), leukopenia (23/28 [82%]), thrombocytopenia (23/23 [100%]), hyperbilirubinemia (27/28 [97%]), hypoalbuminemia (26/28 [93%]), reduced (18/28 [64%]) or low normal (10/28 [36%]) serum ALP activity, and hyponatremia (23/28 [82%]). Reduced ALP activity was unique to cats with feline cytauxzoonosis relative to hepatic lipidosis and cholangiohepatitis. No correlation between the severity of anemia and the magnitude of hyperbilirubinemia was identified in feline cytauxzoonosis patients. CLINICAL RELEVANCE The combination of nonregenerative anemia, leukopenia, thrombocytopenia, hyperbilirubinemia, and reduced serum ALP activity in icteric cats may increase the clinical suspicion, but is not pathognomonic, for acute feline cytauxzoonosis. Hematologic and serum biochemical abnormalities of naturally acquired feline cytauxzoonosis are like those reported with feline bacterial sepsis. Blood smear evaluation for intraerythrocytic Cytauxzoon felis piroplasms, tissue aspirates for schizont-laden macrophages, and/or molecular testing are required to diagnose feline cytauxzoonosis.
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Affiliation(s)
- Brandy C Kastl
- 1Kansas State Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS
- 2Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS
| | - Nora L Springer
- 1Kansas State Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, Manhattan, KS
- 2Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS
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Yahia A, Szlávecz Á, Knopp JL, Norfiza Abdul Razak N, Abu Samah A, Shaw G, Chase JG, Benyo B. Estimating Enhanced Endogenous Glucose Production in Intensive Care Unit Patients with Severe Insulin Resistance. J Diabetes Sci Technol 2022; 16:1208-1219. [PMID: 34078114 PMCID: PMC9445352 DOI: 10.1177/19322968211018260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Critically ill ICU patients frequently experience acute insulin resistance and increased endogenous glucose production, manifesting as stress-induced hyperglycemia and hyperinsulinemia. STAR (Stochastic TARgeted) is a glycemic control protocol, which directly manages inter- and intra- patient variability using model-based insulin sensitivity (SI). The model behind STAR assumes a population constant for endogenous glucose production (EGP), which is not otherwise identifiable. OBJECTIVE This study analyses the effect of estimating EGP for ICU patients with very low SI (severe insulin resistance) and its impact on identified, model-based insulin sensitivity identification, modeling accuracy, and model-based glycemic clinical control. METHODS Using clinical data from 717 STAR patients in 3 independent cohorts (Hungary, New Zealand, and Malaysia), insulin sensitivity, time of insulin resistance, and EGP values are analyzed. A method is presented to estimate EGP in the presence of non-physiologically low SI. Performance is assessed via model accuracy. RESULTS Results show 22%-62% of patients experience 1+ episodes of severe insulin resistance, representing 0.87%-9.00% of hours. Episodes primarily occur in the first 24 h, matching clinical expectations. The Malaysian cohort is most affected. In this subset of hours, constant model-based EGP values can bias identified SI and increase blood glucose (BG) fitting error. Using the EGP estimation method presented in these constrained hours significantly reduced BG fitting errors. CONCLUSIONS Patients early in ICU stay may have significantly increased EGP. Increasing modeled EGP in model-based glycemic control can improve control accuracy in these hours. The results provide new insight into the frequency and level of significantly increased EGP in critical illness.
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Affiliation(s)
- Anane Yahia
- Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary
- Anane Yahia, Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, 2. Magyar tudosok Blvd., Budapest, H-1117, Hungary.
| | - Ákos Szlávecz
- Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary
| | - Jennifer L. Knopp
- Mechanical Engineering, Centre of Bio-Engineering, University of Canterbury, Christchurch, NZ
| | | | - Asma Abu Samah
- Institute of Energy Infrastructure, Universiti Tenaga Nasional, Jalan Ikram-UNITEN, Kajang, Selangor, Malaysia
| | - Geoff Shaw
- Mechanical Engineering, Centre of Bio-Engineering, University of Canterbury, Christchurch, NZ
| | - J. Geoffrey Chase
- Mechanical Engineering, Centre of Bio-Engineering, University of Canterbury, Christchurch, NZ
| | - Balazs Benyo
- Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary
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Wang YF, Li JW, Wang DP, Jin K, Hui JJ, Xu HY. Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function. Drug Des Devel Ther 2022; 16:1697-1711. [PMID: 35693534 PMCID: PMC9176233 DOI: 10.2147/dddt.s360348] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/28/2022] [Indexed: 12/19/2022] Open
Abstract
Intestinal barrier injury and hyperglycemia are common in patients with sepsis. Bacteria translocation and systemic inflammatory response caused by intestinal barrier injury play a significant role in sepsis occurrence and deterioration, while hyperglycemia is linked to adverse outcomes in sepsis. Previous studies have shown that hyperglycemia is an independent risk factor for intestinal barrier injury. Concurrently, increasing evidence has indicated that some anti-hyperglycemic agents not only improve intestinal barrier function but are also beneficial in managing sepsis-induced organ dysfunction. Therefore, we assume that these agents can block or reduce the severity of sepsis by improving intestinal barrier function. Accordingly, we explicated the connection between sepsis, intestinal barrier, and hyperglycemia, overviewed the evidence on improving intestinal barrier function and alleviating sepsis-induced organ dysfunction by anti-hyperglycemic agents (eg, metformin, peroxisome proliferators activated receptor-γ agonists, berberine, and curcumin), and summarized some common characteristics of these agents to provide a new perspective in the adjuvant treatment of sepsis.
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Affiliation(s)
- Yi-Feng Wang
- Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, People's Republic of China
| | - Jia-Wei Li
- Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, People's Republic of China
| | - Da-Peng Wang
- Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, People's Republic of China
| | - Ke Jin
- Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, People's Republic of China
| | - Jiao-Jie Hui
- Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, People's Republic of China
| | - Hong-Yang Xu
- Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, People's Republic of China
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Norris T, Razieh C, Yates T, Zaccardi F, Gillies CL, Chudasama YV, Rowlands A, Davies MJ, McCann GP, Banerjee A, Docherty AB, Openshaw PJ, Baillie JK, Semple MG, Lawson CA, Khunti K. Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19. Diabetes Care 2022; 45:1132-1140. [PMID: 35275994 PMCID: PMC9174963 DOI: 10.2337/dc21-1709] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 01/30/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.
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Affiliation(s)
- Tom Norris
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, U.K
| | - Cameron Razieh
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
| | - Francesco Zaccardi
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, U.K
| | - Clare L. Gillies
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, U.K
| | - Yogini V. Chudasama
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, U.K
| | - Alex Rowlands
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
| | - Melanie J. Davies
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
| | - Gerry P. McCann
- National Institute for Health Research Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
- Cardiovascular Sciences Department, University of Leicester, Leicester, U.K
| | - Amitava Banerjee
- Institute of Health Informatics, University College London, London, U.K
| | - Annemarie B. Docherty
- Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, U.K
- Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, U.K
| | | | | | - Malcolm G. Semple
- National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, U.K
- Respiratory Medicine, Alder Hey Children’s Hospital, Liverpool, U.K
| | - Claire A. Lawson
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, U.K
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, U.K
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research Applied Research Collaboration–East Midlands, Leicester General Hospital, Leicester, U.K
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Zhang L, Xu J, Qi X, Tao Z, Yang Z, Chen W, Wang X, Pan T, Dai Y, Tian R, Chen Y, Tang B, Liu Z, Tan R, Qu H, Yu Y, Liu J. Development and Validation of a Nomogram for Predicting the Risk of Coronavirus-Associated Acute Respiratory Distress Syndrome: A Retrospective Cohort Study. Infect Drug Resist 2022; 15:2371-2381. [PMID: 35528184 PMCID: PMC9075028 DOI: 10.2147/idr.s348278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 02/12/2022] [Indexed: 12/15/2022] Open
Abstract
Background Since the outbreak of coronavirus disease (COVID-19) in December 2019 in Wuhan, it has spread rapidly worldwide. We aimed to establish and validate a nomogram that predicts the probability of coronavirus-associated acute respiratory distress syndrome (CARDS). Methods In this single-centre, retrospective study, 261 patients with COVID-19 were recruited using positive reverse transcription–polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 in Tongji Hospital at Huazhong University of Science and Technology (Wuhan, China). These patients were randomly distributed into the training cohort (75%) and the validation cohort (25%). The factors included in the nomogram were determined using univariate and multivariate logistic regression analyses based on the training cohort. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in the training and validation cohorts. Results Independent predictive factors, including fasting plasma glucose, platelet, D-dimer, and cTnI, were determined using the nomogram. In the training cohort, the AUC and concordance index were 0.93. Similarly, in the validation cohort, the nomogram still showed great distinction (AUC: 0.92) and better calibration. The calibration plot also showed a high degree of agreement between the predicted and actual probabilities of CARDS. In addition, the DCA proved that the nomogram was clinically beneficial. Conclusion Based on the results of laboratory tests, we established a predictive model for acute respiratory distress syndrome in patients with COVID-19. This model shows good performance and can be used clinically to identify CARDS early. Trial Registration Ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (No.:(2020) Linlun-34th).
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Affiliation(s)
- Li Zhang
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Jing Xu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Xiaoling Qi
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Zheying Tao
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Zhitao Yang
- Emergency Department, Ruijin Hospital affiliate to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Wei Chen
- Department of Pulmonary and Critical Care Medicine, Ruijin Hospital Affiliate to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Xiaoli Wang
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Tingting Pan
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Yunqi Dai
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Rui Tian
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Yang Chen
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Bin Tang
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Zhaojun Liu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Ruoming Tan
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Hongping Qu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Yue Yu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Jialin Liu
- Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Correspondence: Jialin Liu; Yue Yu, Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, People’s Republic of China, Email ;
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Kapłan C, Kalemba A, Krok M, Krzych Ł. Effect of Treatment and Nutrition on Glycemic Variability in Critically Ill Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19084717. [PMID: 35457586 PMCID: PMC9026687 DOI: 10.3390/ijerph19084717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/09/2022] [Accepted: 04/10/2022] [Indexed: 02/04/2023]
Abstract
Nondiabetic hyperglycemia is a dangerous metabolic phenomenon in the intensive care unit. Inattentive treatment of glycemic disorders is a serious health hazard promoting negative outcomes. The aim of our study was to assess glycemic variability and its basic determinants, and to verify its relationship with mortality in patients hospitalized in a mixed ICU (intensive care unit). The medical records of 37 patients hospitalized 13 January−29 February 2020 were analyzed prospectively. The BG (blood glucose) variability during the stay was assessed using two definitions, i.e., the value of standard deviation (SD) from all the measurements performed and the coefficient of variation (CV). A correlation between the BG variability and insulin dose was observed (SD: R = 0.559; p < 0.01; CV: R = 0.621; p < 0.01). There was also a correlation between the BG variability and the total energy daily dose (SD: R = 0.373; p = 0.02; CV: R = 0.364; p = 0.03). Glycemic variability was higher among patients to whom treatment with adrenalin (p = 0.0218) or steroid (p = 0.0292) was applied. The BG variability, expressed using SD, was associated with ICU mortality (ROC = 0.806; 95% CI: 0.643−0.917; p = 0.0014). The BG variability in the ICU setting arises from the loss of balance between the supplied energy and the applied insulin dose and may be associated with a worse prognosis.
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Affiliation(s)
- Cezary Kapłan
- Students’ Scientific Society, Department of Anesthesiology and Intensive Care, School of Medicine in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (C.K.); (M.K.)
| | - Alicja Kalemba
- Students’ Scientific Society, Department of Anesthesiology and Intensive Care, School of Medicine in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (C.K.); (M.K.)
- Correspondence:
| | - Monika Krok
- Students’ Scientific Society, Department of Anesthesiology and Intensive Care, School of Medicine in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (C.K.); (M.K.)
| | - Łukasz Krzych
- Department of Anesthesiology and Intensive Care, School of Medicine in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland;
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Chai C, Chen K, Li S, Cheng G, Wang W, Wang H, Wei D, Peng C, Sun Q, Tang Z. Effect of elevated fasting blood glucose level on the one-year mortality and sequelae in hospitalized COVID-19 patients: a bidirectional cohort study. J Med Virol 2022; 94:3240-3250. [PMID: 35357022 PMCID: PMC9088618 DOI: 10.1002/jmv.27737] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 02/04/2022] [Accepted: 03/22/2022] [Indexed: 12/15/2022]
Abstract
To observe the predictive effect of fasting blood glucose (FBG) level on the prognosis, clinical sequelae, and pulmonary absorption in hospitalized coronavirus disease 2019 (COVID‐19) patients with and without a history of diabetes, respectively, and to evaluate the correlation between the dynamic changes of FBG and poor prognosis. In this bidirectional cohort study, we enrolled 2545 hospitalized COVID‐19 patients (439 diabetics and 2106 without a diabetic history) and followed up for 1 year. The patients were divided according to the level of admission FBG. The dynamic changes of FBG were compared between the survival and the death cases. The prediction effect of FBG on 1‐year mortality and sequelae was analyzed. The 1‐year all cause mortality rate and in‐hospital mortality rate of COVID‐19 patients were J‐curve correlated with FBG (p < 0.001 for both in the nondiabetic history group, p = 0.004 and p = 0.01 in the diabetic history group). FBG ≥ 7.0 mmol/L had a higher risk of developing sequelae (p = 0.025) and have slower recovery of abnormal lung scans (p < 0.001) in patients who denied a history of diabetes. Multivariable Cox regression analysis showed that FBG ≥ 7.0 mmol/L was an independent risk factor for the mortality of COVID‐19 regardless of the presence or deny a history of diabetes (hazard atio [HR] = 10.63, 95% confidence interval [CI]: 7.15−15.83, p < 0.001; HR = 3.9, 95% CI: 1.56−9.77, p = 0.004, respectively). Our study shows that FBG ≥ 7.0 mmol/L can be a predictive factor of 1‐year all‐cause mortality in COVID‐19 patients, independent of diabetes history. FBG ≥ 7.0 mmol/L has an advantage in predicting the severity, clinical sequelae, and pulmonary absorption in COVID‐19 patients without a history of diabetes. Early detection, timely treatment, and strict control of blood glucose when finding hyperglycemia in COVID‐19 patients (with or without diabetes) are critical for their prognosis.
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Affiliation(s)
- Chen Chai
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Department of Emergency Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430022, China
| | - Kui Chen
- Department of Emergency Medicine, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, China
| | - Shoupeng Li
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Department of Emergency Medicine, Huanan Hospital, Shenzhen University, Shenzhen, 518111, China
| | - Gang Cheng
- Computer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wendan Wang
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hongxiang Wang
- Department of hematology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China
| | - Dunshuang Wei
- Department of Emergency Medicine, the Third People's Hospital of Hubei Province, Wuhan, 430030, China
| | - Cao Peng
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qi Sun
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zehai Tang
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Srinivasan V, Lee JH, Menon K, Zimmerman JJ, Bembea MM, Agus MSD. Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference. Pediatrics 2022; 149:S84-S90. [PMID: 34970672 DOI: 10.1542/peds.2021-052888m] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2021] [Indexed: 11/24/2022] Open
Abstract
CONTEXT Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism. OBJECTIVE To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded. DATA EXTRACTION Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers. RESULTS The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 μg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation. LIMITATIONS These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing. CONCLUSIONS We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.
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Affiliation(s)
- Vijay Srinivasan
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Jan Hau Lee
- Children's Intensive Care Unit, KK Women's and Children's Hospital and Duke-National University of Singapore Medical School, Singapore
| | - Kusum Menon
- Division of Pediatric Critical Care, Department of Pediatrics, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada
| | - Jerry J Zimmerman
- Pediatric Critical Care Medicine, Seattle Children's Hospital, Harborview Medical Center and School of Medicine, University of Washington, Seattle, Washington
| | - Melania M Bembea
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Michael S D Agus
- Division of Medical Critical Care, Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts
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Valente T, Valente F, Lucchesi MBB, Punaro GR, Mouro MG, Gabbay MAL, Higa EMS, Dib SA. Relationship between short and long-term glycemic variability and oxidative stress in type 1 diabetes mellitus under daily life insulin treatment. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2021; 65:570-578. [PMID: 33740334 PMCID: PMC10528580 DOI: 10.20945/2359-3997000000338] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 12/17/2020] [Indexed: 11/23/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the heterogeneity of the association between glycemic variability and oxidative stress markers in T1DM patients under daily life insulin treatment. METHODS We studied, in a cross-sectional analysis, 76 T1DM patients without clinical chronic diabetes complications and 22 healthy individuals. Were evaluated the short-term glycemic variability (STGV), long-term glycemic variability (LTGV), oxidative stress markers [8-isoprostaglandin-F2α (Ur-8-iso-PGF2α), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and erythrocytes reduced/oxidized glutathione (GSH/GSSG)] and biochemical dosages (glycaemia, HbA1c, lipidogram, albuminuria). RESULTS Plasmatic NO was positively associated with LTGV (last year average of HbA1c) (8.7 ± 1.6% or 71 ± 18 mmol) (rS: 0.278; p: 0.042). Plasmatic TBARS, erythrocytes GSH/GSSH and Ur-8-iso-PGF-2α didn't show correlation with glycemic variability. GSH/GSSG was inversely correlated with LDL-cholesterol (rS: - 0.417; p: 0.047) and triglycerides (rS: -0.521; p: 0.013). Albuminuria was positive correlated with age (rS: 0.340; p: 0.002), plasmatic NO (rS: 0.267; p 0.049) and TBARS (rS: 0.327; p: 0.015). CONCLUSION In daily life insulin treatment, young T1DM patients have higher plasmatic NO than healthy subjects. However, the correlation between glycemic variability and oxidative stress markers is heterogeneous. Lipid profile and albuminuria are associated with different oxidative stress markers. These data collaborate to explain the controversial results in this issue.
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Affiliation(s)
- Tatiana Valente
- Departamento de Medicina, Divisão de Endocrinologia, Centro de Diabetes da Universidade Federal de São Paulo, São Paulo, SP, Brasil,
| | - Fernando Valente
- Departamento de Medicina, Divisão de Endocrinologia, Centro de Diabetes da Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Maria Beatriz Bastos Lucchesi
- Departamento de Medicina, Divisão de Endocrinologia, Centro de Diabetes da Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Giovana Rita Punaro
- Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Margaret Gori Mouro
- Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Monica Andrade Lima Gabbay
- Departamento de Medicina, Divisão de Endocrinologia, Centro de Diabetes da Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Elisa Mieko Suemitsu Higa
- Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Sergio Atala Dib
- Departamento de Medicina, Divisão de Endocrinologia, Centro de Diabetes da Universidade Federal de São Paulo, São Paulo, SP, Brasil
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Peptide VSAK maintains tissue glucose uptake and attenuates pro-inflammatory responses caused by LPS in an experimental model of the systemic inflammatory response syndrome: a PET study. Sci Rep 2021; 11:14752. [PMID: 34285283 PMCID: PMC8292390 DOI: 10.1038/s41598-021-94224-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 07/07/2021] [Indexed: 12/30/2022] Open
Abstract
The present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.
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Dutton JS, Hinman SS, Kim R, Attayek PJ, Maurer M, Sims CS, Allbritton NL. Hyperglycemia minimally alters primary self-renewing human colonic epithelial cells while TNFα-promotes severe intestinal epithelial dysfunction. Integr Biol (Camb) 2021; 13:139-152. [PMID: 33989405 PMCID: PMC8204630 DOI: 10.1093/intbio/zyab008] [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: 12/10/2020] [Revised: 03/06/2021] [Accepted: 04/16/2021] [Indexed: 11/15/2022]
Abstract
Hyperglycemia is thought to increase production of inflammatory cytokines and permeability of the large intestine. Resulting intestinal inflammation is then often characterized by excess secretion of tumor necrosis factor alpha (TNFα). Thus, hyperglycemia in hospitalized patients suffering from severe trauma or disease is frequently accompanied by TNFα secretion, and the combined impact of these insults on the intestinal epithelium is poorly understood. This study utilized a simple yet elegant model of the intestinal epithelium, comprised of primary human intestinal stem cells and their differentiated progeny, to investigate the impact of hyperglycemia and inflammatory factors on the colonic epithelium. When compared to epithelium cultured under conditions of physiologic glucose, cells under hyperglycemic conditions displayed decreased mucin-2 (MUC2), as well as diminished alkaline phosphatase (ALP) activity. Conditions of 60 mM glucose potentiated secretion of the cytokine IL-8 suggesting that cytokine secretion during hyperglycemia may be a source of tissue inflammation. TNFα measurably increased secretion of IL-8 and IL-1β, which was enhanced at 60 mM glucose. Surprisingly, intestinal permeability and paracellular transport were not altered by even extreme levels of hyperglycemia. The presence of TNFα increased MUC2 presence, decreased ALP activity, and negatively impacted monolayer barrier function. When TNFα hyperglycemia and ≤30 mM glucose and were combined, MUC2 and ALP activity remained similar to that of TNFα alone, although synergistic effects were seen at 60 mM glucose. An automated image analysis pipeline was developed to assay changes in properties of the zonula occludens-1 (ZO-1)-demarcated cell boundaries. While hyperglycemia alone had little impact on cell shape and size, cell morphologic properties were extraordinarily sensitive to soluble TNFα. These results suggest that TNFα acted as the dominant modulator of the epithelium relative to glucose, and that control of inflammation rather than glucose may be key to maintaining intestinal homeostasis.
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Affiliation(s)
- Johanna S Dutton
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, NC, USA
| | - Samuel S Hinman
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Raehyun Kim
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Peter J Attayek
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, NC, USA
| | - Mallory Maurer
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, NC, USA
| | - Christopher S Sims
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Nancy L Allbritton
- Department of Bioengineering, University of Washington, Seattle, WA, USA
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46
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Mirzaei F, Khodadadi I, Vafaei SA, Abbasi-Oshaghi E, Tayebinia H, Farahani F. Importance of hyperglycemia in COVID-19 intensive-care patients: Mechanism and treatment strategy. Prim Care Diabetes 2021; 15:409-416. [PMID: 33436320 PMCID: PMC7834268 DOI: 10.1016/j.pcd.2021.01.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 01/03/2021] [Accepted: 01/04/2021] [Indexed: 12/15/2022]
Abstract
This review reported that coronavirus disease 2019 (COVID-19) infected patients with short time bed rest or quarantine and airway inflammation are at more risk of developing hyperglycemia and insulin resistance. This condition can induce oxidative stress, decrease immune system function, impair endothelial function, induce apoptosis, and reduce antioxidant in the lungs. We provide a possible mechanism in severe COVID-19 patients and recommend treatment strategy to reduce mortality rate and prevent adverse outcomes after intensive care unit (ICU).
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Affiliation(s)
- Fatemeh Mirzaei
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Anatomical Sciences, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Iraj Khodadadi
- Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.
| | | | - Ebrahim Abbasi-Oshaghi
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Heidar Tayebinia
- Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Farhad Farahani
- Hearing Impairment Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
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47
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Affinati AH, Wallia A, Gianchandani RY. Severe hyperglycemia and insulin resistance in patients with SARS-CoV-2 infection: a report of two cases. Clin Diabetes Endocrinol 2021; 7:8. [PMID: 33992101 PMCID: PMC8123093 DOI: 10.1186/s40842-021-00121-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 04/27/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Severe insulin resistance is an uncommon finding in patients with type 2 diabetes but is often associated with difficult to managing blood glucose. While severe insulin resistance is most frequently seen in the setting of medication side effects or rare genetic conditions, this report of two cases highlights the presence of severe insulin resistance in the setting of severe COVID-19 and explores how this may contribute to the poor prognosis of patients with diabetes who become infected with SARS-CoV-2. CASE PRESENTATION Here we present the cases of two African-American women with pre-existing type 2 diabetes who developed severe COVID-19 requiring mechanical ventilation and concurrent severe insulin resistance with total daily insulin dose requirements of greater than 5 unit/kg. Both patients received aggressive insulin infusion and subcutaneous insulin therapy to obtain adequate glucose management. As their COVID-19 clinical course improved, their severe insulin resistance improved as well. CONCLUSIONS The association between critical illness and hyperglycemia is well documented in the literature, however severe insulin resistance is not commonly identified and may represent a unique clinical feature of the interaction between SARS-CoV-2 infection and type 2 diabetes.
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Affiliation(s)
- Alison H Affinati
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Domino's Farms (Lobby G, Suite 1500), 24 Frank Lloyd Wright Drive, MI, 48106, Ann Arbor, USA
| | - Amisha Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, IL, Chicago, USA
| | - Roma Y Gianchandani
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Domino's Farms (Lobby G, Suite 1500), 24 Frank Lloyd Wright Drive, MI, 48106, Ann Arbor, USA.
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48
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de Souza Galia WB, Biazi GR, Frasson-Uemura IG, Miksza DR, Zaia CTBV, Zaia DAM, de Souza HM, Bertolini GL. Gluconeogenesis is reduced from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis. Cell Biochem Funct 2021; 39:754-762. [PMID: 33913177 DOI: 10.1002/cbf.3637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 04/12/2021] [Indexed: 11/09/2022]
Abstract
Sepsis induces several metabolic abnormalities, including hypoglycaemia in the most advanced stage of the disease, a risk factor for complications and death. Although hypoglycaemia can be caused by inhibition of hepatic gluconeogenesis, decreased and increased gluconeogenesis were reported in sepsis. Furthermore, gluconeogenesis from glycerol was not yet evaluated in this disease. The main purpose of this study was to investigate the gluconeogenesis from alanine, lactate, pyruvate and glycerol in rats with early (8 hours) and late (18 hours) sepsis. Parameters related to the characterization of sepsis were also evaluated. Sepsis was induced by cecal ligation and puncture and gluconeogenesis was assessed in liver perfusion. Rats with early and late sepsis showed increased lactataemia, depletion of liver glycogen and peripheral insulin resistance, characterizing the establishment of sepsis. Rats with early and late sepsis showed decreased gluconeogenesis from alanine, lactate and pyruvate. Interestingly, gluconeogenesis from glycerol, a precursor that enters in the pathway at a later step, subsequent to the entry of alanine, lactate and pyruvate, was maintained in rats with early and late sepsis. In conclusion, gluconeogenesis is decreased from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis. SIGNIFICANCE OF THE STUDY: The maintenance of gluconeogenesis from glycerol, but not from alanine, lactate and pyruvate, together with the liver glycogen depletion, points the glycerol as an important precursor for the maintenance of glycaemic homeostasis in sepsis. The findings open the possibility of further investigation on the administration of glycerol in the treatment of hypoglycaemia associated with more advanced sepsis.
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Affiliation(s)
| | - Giuliana Regina Biazi
- Department of Physiological Sciences, State University of Londrina, Londrina, Brazil
| | | | - Daniele Romani Miksza
- Department of Physiological Sciences, State University of Londrina, Londrina, Brazil
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Farooq N, Chuan B, Mahmud H, El Khoudary SR, Nouraie SM, Evankovich J, Yang L, Dunlap D, Bain W, Kitsios G, Zhang Y, O’Donnell CP, McVerry BJ, Shah FA. Association of the systemic host immune response with acute hyperglycemia in mechanically ventilated septic patients. PLoS One 2021; 16:e0248853. [PMID: 33755703 PMCID: PMC7987165 DOI: 10.1371/journal.pone.0248853] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 03/07/2021] [Indexed: 12/13/2022] Open
Abstract
Hyperglycemia during sepsis is associated with increased organ dysfunction and higher mortality. The role of the host immune response in development of hyperglycemia during sepsis remains unclear. We performed a retrospective analysis of critically ill adult septic patients requiring mechanical ventilation (n = 153) to study the relationship between hyperglycemia and ten markers of the host injury and immune response measured on the first day of ICU admission (baseline). We determined associations between each biomarker and: (1) glucose, insulin, and c-peptide levels at the time of biomarker collection by Pearson correlation; (2) average glucose and glycemic variability in the first two days of ICU admission by linear regression; and (3) occurrence of hyperglycemia (blood glucose>180mg/dL) by logistic regression. Results were adjusted for age, pre-existing diabetes mellitus, severity of illness, and total insulin and glucocorticoid dose. Baseline plasma levels of ST2 and procalcitonin were positively correlated with average blood glucose and glycemic variability in the first two days of ICU admission in unadjusted and adjusted analyses. Additionally, higher baseline ST2, IL-1ra, procalcitonin, and pentraxin-3 levels were associated with increased risk of hyperglycemia. Our results suggest associations between the host immune response and hyperglycemia in critically ill septic patients particularly implicating the interleukin-1 axis (IL-1ra), the interleukin-33 axis (ST2), and the host response to bacterial infections (procalcitonin, pentraxin-3).
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Affiliation(s)
- Nauman Farooq
- Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Byron Chuan
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Hussain Mahmud
- Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Samar R. El Khoudary
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Seyed Mehdi Nouraie
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - John Evankovich
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Libing Yang
- School of Medicine, Tsinghua University, Haidian District, Beijing, China
| | - Daniel Dunlap
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - William Bain
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States of America
| | - Georgios Kitsios
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Yingze Zhang
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Christopher P. O’Donnell
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Bryan J. McVerry
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Faraaz Ali Shah
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States of America
- * E-mail:
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50
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Prantner D, Nallar S, Richard K, Spiegel D, Collins KD, Vogel SN. Classically activated mouse macrophages produce methylglyoxal that induces a TLR4- and RAGE-independent proinflammatory response. J Leukoc Biol 2021; 109:605-619. [PMID: 32678947 PMCID: PMC7855181 DOI: 10.1002/jlb.3a0520-745rr] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 05/18/2020] [Accepted: 05/19/2020] [Indexed: 01/05/2023] Open
Abstract
The highly reactive compound methylglyoxal (MG) can cause direct damage to cells and tissues by reacting with cellular macromolecules. MG has been identified as a biomarker associated with increased sepsis-induced mortality. Patients undergoing septic shock have significantly elevated circulating MG levels compared to postoperative patients and healthy controls. Furthermore, MG has been implicated in the development of type II diabetes mellitus and Alzheimer's disease. Because MG is generated during glycolysis, we hypothesized that MG may be produced by classically activated (M1) macrophages, possibly contributing to the inflammatory response. LPS and IFN-γ-treated macrophages acquired an M1 phenotype (as evidenced by M1 markers and enhanced glycolysis) and formed MG adducts, MG-H1, MG-H2, and MG-H3, which were detected using antibodies specific for MG-modified proteins (methylglyoxal 5-hydro-5-methylimidazolones). MG adducts were also increased in the lungs of LPS-treated mice. Macrophages treated with LPS and IFN-γ also exhibited decreased expression of glyoxalase 1 (Glo1), an enzyme that metabolizes MG. Concentrations of exogenous, purified MG > 0.5 mM were toxic to macrophages; however, a nontoxic dose of 0.3 mM induced TNF-α and IL-1β, albeit to a lesser extent than LPS stimulation. Despite prior evidence that MG adducts may signal through "receptor for advanced glycation endproducts" (RAGE), MG-mediated cell death and cytokine induction by exogenous MG was RAGE-independent in primary macrophages. Finally, RAGE-deficient mice did not exhibit a significant survival advantage following lethal LPS injection. Overall, our evidence suggests that MG may be produced by M1 macrophages during sepsis, following IFN-γ-dependent down-regulation of Glo1, contributing to over-exuberant inflammation.
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Affiliation(s)
- Daniel Prantner
- Dept. of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD
| | - Shreeram Nallar
- Dept. of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD
| | - Katharina Richard
- Dept. of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD
| | - David Spiegel
- Department of Chemistry, Yale University, New Haven, CT
| | - Kim D. Collins
- Dept. of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD
- Institute of Marine and Environmental Technology (IMET), University of Maryland, Baltimore, Baltimore, MD
| | - Stefanie N. Vogel
- Dept. of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD
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