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Growing evidence highlights the importance of tumor endothelial cells (TECs) in the tumor microenvironment (TME) for promoting tumor growth and evading immune responses. Immunomodulatory endothelial cells (IMECs) represent a distinct plastic phenotype of ECs that exerts the ability to modulate immunity in health and disease. This review discusses our current understanding of IMECs in cancer biology, scrutinizing insights from single-cell reports to compare their characteristics and function dynamics across diverse tumor types, conditions, and species. We investigate possible implications of exploiting IMECs in the context of cancer treatment, particularly examining their influence on the efficacy of existing therapies and the potential to leverage them as targets in optimizing immunotherapeutic strategies., Competing Interests: Declaration of interests None are declared by the authors., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The ketogenic diet is a very low carbohydrate diet known for its ability to reduce weight and counteract hyperglycaemia. However, ketogenic diets recommend an increased intake of fats, raising concerns about cardiometabolic risk in adults. Due to the higher intake of fats in the ketogenic diet, there is significant variability in outcomes of lipid metabolism in the population. Interventions have reported improvements in lipid profile while other studies did not find changes, and there are reports of increased low density lipoprotein (LDL) and triglyceride values. Hence, this is a protocol for a systematic review of the published literature and a summary of the effect of ketogenic diets on lipid metabolism in adults., Methods and Analysis: Five databases (PubMed, Embase, Scopus, Cochrane Library and Web of Science) will be searched for studies on ketogenic diets in adult populations. Studies will be included if they report results from ketogenic diet interventions among adults. Exclusion is populations with diagnosed neurological disorders. Two reviewers will independently screen retrieved citations, extract data and appraise the risk of bias. Quantitative estimates (eg, standardised mean difference) measuring the change in the total cholesterol, LDL and triglyceride concentration will be pooled using random effects meta-analysis to produce one summarised weighted estimate. Sources of heterogeneity will be explored using subgroup analysis. This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA), and the final review will be reported following the PRISMA 2020 guidelines., Ethics and Dissemination: The present protocol and the systematic review to be carried out do not require ethics clearance. The data source will be published studies. This review will provide estimates to inform the public about the effect of ketogenic diets on lipid metabolism and the possible peril of increasing cardiometabolic risk. The results will be published in a peer-reviewed journal., Prospero Registration Number: CRD42022309665., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This Rapid Practice Guideline (RPG) aimed to provide evidence‑based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research., Methods: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities., Results: Data from 17 randomized clinical trials (n=898) and 9 observational studies (n=1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied., Conclusion: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence., (Copyright © 2024 International Anesthesia Research Society.)

Objectives: To conduct a systematic review and meta-analysis assessing whether the use of antipsychotic medications in critically ill adult patients with delirium impacts patient-important outcomes., Data Sources: A medical librarian searched Ovid MEDLINE, EMBASE, APA PsycInfo, and Wiley's Cochrane Library as well as clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2023., Study Selection: Independently and in duplicate, reviewers screened abstracts and titles for eligibility, then full text of qualifying studies. We included parallel-group randomized controlled trials (RCTs) that included critically ill adult patients with delirium. The intervention group was required to receive antipsychotic medications at any dose, whereas the control group received usual care or placebo., Data Extraction: Reviewers extracted data independently and in duplicate using a piloted abstraction form. Statistical analyses were conducted using RevMan software (version 5.4)., Data Synthesis: Five RCTs ( n = 1750) met eligibility criteria. The use of antipsychotic medications compared with placebo did not increase the number of delirium- or coma-free days (mean difference 0.90 d; 95% CI, -0.32 to 2.12; moderate certainty), nor did it result in a difference in mortality, duration of mechanical ventilation, ICU, or hospital length of stay. The use of antipsychotics did not result in an increased risk of adverse events (risk ratio 1.27; 95% CI, 0.71-2.30; high certainty). Subgroup analysis of typical versus atypical antipsychotics did not identify any subgroup effect for any outcome., Conclusions: In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in delirium- or coma-free days when delirious critically ill adults are treated with antipsychotic medications. Further studies in the subset of patients with hyperactive delirium may be of benefit., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians., Methods: We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the use versus no use of albumin., Results: A total of 1248 respondents participated, with a mean response rate of 37%, ranging from 18% to 75% across 21 countries. Respondents mainly worked in mixed ICUs and 92% were specialists in intensive care medicine. The reported use of albumin in general shock varied as 18% reported 'almost never', 22% 'rarely', 34% 'occasionally', 22% 'frequently' and 4% 'almost always' using albumin. In septic shock, 19% reported 'almost never', 22% 'rarely', 29% 'occasionally', 22% 'frequently' and 7% 'almost always' using albumin. Physicians' preferences were more consistent for haemorrhagic- and cardiogenic shock, with more than 45% reporting 'almost never' using albumin. While the reported use of albumin for other purposes than resuscitation was infrequent (40%-85% reported 'almost never' for five other indications), the most frequent other indications were low serum albumin levels and improvement of the efficacy of diuretics. Most respondents (93%) would randomise adult ICU patients with shock to a trial of albumin versus no albumin., Conclusions: In this international survey, the reported preferences for the use of albumin in adult ICU patients with shock varied considerably among surveyed ICU physicians. The support for a future randomised trial was high., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: This is the first of three parts of the clinical practice guideline from the European Society of Intensive Care Medicine (ESICM) on resuscitation fluids in adult critically ill patients. This part addresses fluid choice and the other two will separately address fluid amount and fluid removal., Methods: This guideline was formulated by an international panel of clinical experts and methodologists. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was applied to evaluate the certainty of evidence and to move from evidence to decision., Results: For volume expansion, the guideline provides conditional recommendations for using crystalloids rather than albumin in critically ill patients in general (moderate certainty of evidence), in patients with sepsis (moderate certainty of evidence), in patients with acute respiratory failure (very low certainty of evidence) and in patients in the perioperative period and patients at risk for bleeding (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than albumin in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using albumin rather than crystalloids in patients with cirrhosis (very low certainty of evidence). The guideline provides conditional recommendations for using balanced crystalloids rather than isotonic saline in critically ill patients in general (low certainty of evidence), in patients with sepsis (low certainty of evidence) and in patients with kidney injury (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than balanced crystalloids in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using isotonic crystalloids rather than small-volume hypertonic crystalloids in critically ill patients in general (very low certainty of evidence)., Conclusions: This guideline provides eleven recommendations to inform clinicians on resuscitation fluid choice in critically ill patients., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To describe the productivity, performance, and impact of medical research in the Arab world countries., Methods: We carried out a bibliometric analysis using Clarivate Analytics databases from January 2017 to March 2023. We reported research productivity, national and international research collaboration patterns, impact of Arab medical research output compared to the global average, top medical journals publishing Arab-affiliated research, and performance of the most productive Arab institutions., Results: The Arab world contributed 2.72% to global medical research publication, with a citation impact of 11.98 compared to the global impact of 12.02. Qatar, Lebanon, and Saudi Arabia led medical research publications per million population among Arab countries, ranking 26th, 36th, and 37th globally. Medical research publications increased by 87% annually from 2017-2022, with 70% of research originating from Saudi Arabia and Egypt. National collaborations accounted for 15% of Arab world publications, while international collaborations represented 66%. The median impact factor across the top 20 medical journals with Arab-affiliated authors was 5.14, with 50% being quartile one journals. The top 10 Arab-origin medical journals had a median impact factor of 3.13. Approximately 80% of the top 20 Arab institutions were academic, with a median publication count of 3,162.5 and a median citation impact of 14.5., Conclusion: The study provides insights into the state of medical research in the Arab countries, indicating room for improvement in the region's medical research., (Copyright: © Saudi Medical Journal.)

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago. The definition, diagnosis, and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians, enabling a better understanding of this disease and more targeted treatment for patients. We describe the definition, presentation, and diagnosis of eosinophilic esophagitis including management, challenges, and future directions in children. The definition, diagnosis, and management of eosinophilic esophagitis have evolved over the last 50 years. Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients. We describe the definition, presentation, diagnosis, management, and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC., (© 2024 John Wiley & Sons Ltd.)

Rationale: Fever is frequently an early indicator of infection and often requires rigorous diagnostic evaluation., Objectives: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology., Panel Design: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline., Methods: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements., Results: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data., Conclusions: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue-including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers., Competing Interests: Supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. Van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antibiotic Resistance Leadership Group UM1AI104681), the NIH, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics Limited, Hylomorph, BioFire, Shionogi, IDSA, NBME, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antimicrobial Resistance Leadership Group UM1AI104681), the National Institutes of Health, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics, Hylomorph, BioFire, Shionogi, Infectious Diseases Society of America, National Board of Medical Examiners, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST Diagnostics, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Competing Interests: Conflicts of interest were reviewed and adjudicated by the co-chairs and co-vice chairs of the guidelines. In the event an individual disclosed a conflict or potential conflict by submitted form or verbally during the process of guidelines, those individuals abstained from voting on related questions. The taskforce followed all procedures as documented in the American College of Critical Care Medicine/Society of Critical Care Medicine (SCCM) Standard Operating Procedures Manual. Drs. Singbartl, Nanchal, Killian, Olson, Karvellas, Subramanian, and Truwit disclosed authorship on several related articles with potential intellectual conflicts explored and adjudicated. Dr. Dionne described volunteer service for Canadian Association of Gastroenterology, American College of Gastroenterology, American Gastroenterological Association, and European Society of Intensive Care Medicine. Dr. Hyzy described volunteer service for American Thoracic Society, Quality Improvement and Implementation Committee, and the SCCM Finance Committee as well as service as an expert witness in a previous medical case involving this subject matter. Taylor advised of service as an author on the SCCM/American Society for Parenteral and Enteral Nutrition (ASPEN) nutrition guidelines and service on the ASPEN research committee. Dr. Huang disclosed service on the American College of Emergency Physicians sepsis task force. Dr. Karvellas disclosed service on an acute liver failure study group. Dr. Hyzy and Dr. Olson disclosed being expert witnesses. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objectives: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU., Design: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development., Interventions: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements., Measurements and Main Results: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence., Conclusions: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence., Competing Interests: Conflicts of interest were reviewed and adjudicated by the co-chairs and co-vice chairs of the guidelines. In the event an individual disclosed a conflict or potential conflict by submitted form or verbally during the process of guidelines, those individuals abstained from voting on related questions. The taskforce followed all procedures as documented in the American College of Critical Care Medicine/Society of Critical Care Medicine (SCCM) Standard Operating Procedures Manual. Drs. Singbartl, Nanchal, Killian, Olson, Karvellas, Subramanian, and Truwit disclosed authorship on several related articles with potential intellectual conflicts explored and adjudicated. Dr. Dionne described volunteer service for Canadian Association of Gastroenterology, American College of Gastroenterology, American Gastroenterological Association, and European Society of Intensive Care Medicine. Dr. Hyzy described volunteer service for American Thoracic Society, Quality Improvement and Implementation Committee, and the SCCM Finance Committee as well as service as an expert witness in a previous medical case involving this subject matter. Dr. Taylor advised of service as an author on the SCCM/American Society of Parenteral and Enteral Nutrition (ASPEN) nutrition guidelines and service on the ASPEN research committee. Dr. Huang disclosed service on the American College of Emergency Physicians Sepsis Task Force. Dr. Karvellas disclosed service on an Acute Liver Failure Study Group. Dr. Hollenberg disclosed that he is a member of American College of Chest Physicians, American Heart Association, and American College of Cardiology. Dr. Olson disclosed that she is a member of American Association for the Study of Liver Disease. Dr. Steadman disclosed that he is a co-author on “Management of the Critically Ill Patient with Cirrhosis: A Multidisciplinary Perspective.” J Hepatology 2015 pending publication, and that he is currently writing guidelines for Anesthesiology Transplant fellowship for the International Liver Transplant Society. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine.)

Objective: To conduct a systematic review and meta-analysis to determine whether targeting a higher mean arterial pressure (MAP) compared with a lower MAP in adults with shock results in differences in patient important outcomes., Data Sources: We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov through May 2021., Study Selection: Titles and abstracts were screened independently and in duplicate to identify potentially eligible studies, then full text for final eligibility. We included parallel-group randomized controlled trials in adult patients with a diagnosis of shock requiring vasoactive medications. The higher MAP group was required to receive vasoactive medications to target a higher MAP as established by study authors, whereas the lower MAP group received vasoactive medications to target lower MAP., Data Extraction: In triplicate, reviewers independently extracted data using a prepiloted abstraction form. Statistical analyses were conducted using the RevMan software Version 5.3., Data Synthesis: Six randomized controlled trials (n = 3,690) met eligibility criteria. Targeting a higher MAP (75-85 mm Hg) compared with lower MAP of 65 mm Hg resulted in no difference in mortality (relative risk [RR], 1.06; 95% CI, 0.98-1.15; I2 = 0%; p = 0.12; moderate certainty. Targeting a higher MAP resulted in no difference in the risk of undergoing renal replacement therapy (RR, 0.96; 95% CI, 0.83-1.11; I2 = 24%; p = 0.57; moderate certainty); however, a subgroup analysis comparing patients with and without chronic hypertension demonstrated that a higher MAP may reduce the risk of undergoing renal replacement therapy (RR, 0.83; 95% CI, 0.71-0.98; I2 = 0%; p = 0.02)., Conclusions: In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in mortality when a higher MAP is targeted in critically ill adult patients with shock. Further studies are needed to determine the impact of mean arterial pressure on need for renal replacement therapy in this population., Competing Interests: Dr. Granholm’s institution received funding from Sygeforsikringen “danmark.” The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Coronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors. The study included 211 laboratory-confirmed cases suffering from a mild form of the disease and completing their isolation period at a non-hospital center in the United Arab Emirates. Demographic and clinical information was collected by standardized questionnaire and from the medical records of the patient. Of the 211 participants, 25% tested negative in both sample types at the time of this study and 53% of the remaining patients had detectable viral RNA in their stools. A positive fecal viral test was associated with male gender, diarrhea as a symptom, and hospitalization during infection. A positive correlation was also observed between a delayed onset of symptoms and a positive stool test. Viral load in stools positively correlated with, being overweight, exercising, taking antibiotics in the last 3 months and blood type O. The viral load in nasopharyngeal swabs, on the other hand, was higher for blood type A, and rhesus positive (Rh factor). Regression analysis showed no correlation between the viral loads measured in stool and nasopharyngeal samples in any given patient. The results of this work highlight the factors associated with a higher viral count in each sample. It also shows the importance of stool sample analysis for the follow-up and diagnosis of recovering COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist.

The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines placed increased emphasis on a diverse, global perspective, as well as on the long-term sequelae of sepsis experienced by patients and their families. The guidelines encompassed the following sections: 1) screening and early treatment; 2) infection; 3) hemodynamic management; 4) ventilation; 5) additional therapies; and 6) goals of care and long-term outcomes. In this review, we provide a summary of key recommendations of interest to the practicing clinician, which are either novel or require a change in practice, as well as those for which the evidence has substantially evolved in the 5 years since the 2016 iteration of the Guidelines. Rather than reviewing the underlying evidence, we emphasize the practical aspects of interpretation, dissemination, and implementation of these recommendations in the clinical setting.

Background: The impact of clinical proficiency on individual student scores on the National Board of Medical Examiners (NBME) Subject Examinations remains uncertain. We hypothesised that increasing the length of time spent in a clinical environment would augment students' performance., Methods: Performance on the NBME Subject Examination in Internal Medicine (NBME-IM) of three student cohorts was observed longitudinally. Scores at the end of two unique internal medicine clerkships held at the third and fourth years were compared. The score differences between the two administrations were compared using paired t -tests, and the effect size was measured using Cohen's d . Moreover, linear regression was used to assess the correlation between the NBME-IM score gains and performance on a pre-clinical Comprehensive Basic Science Examination (CBSE). A two-tailed p -value <0.05 was considered significant., Results: Of the 236 students enrolled during the third year, age, gender, CBSE, and NBME-IM scores were similar across all cohorts. The normalised score gain on the NBME-IM at the fourth year was 9.5% (range -38 to +45%) with a Cohen's d of 0.47. However, a larger effect size with a Cohen's d value of 0.96 was observed among poorly scoring students. Performance on the CBSE was a significant predictor of score gain on the NBME-IM ( R 0.51, R 2 0.26, p -value < 0.001)., Conclusions: Despite the increased length of clinical exposure, modest improvement in students' performance on repeated NBME-IM examination was observed. Medical educators need to reconsider how the NBME-IM is used in clerkship assessments., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2022.)

Hospitalized patients with coronavirus disease 2019 (COVID-19), particularly those admitted to the intensive care unit (ICU) are at high risk of morbidity and mortality. Several observational studies have described hemostatic derangements and thrombotic complications in patients with COVID-19. The aim of this review article is to summarize the current evidence on pathologic findings, pathophysiology, coagulation and hemostatic abnormalities, D-dimer's role in prognostication epidemiology and risk factors of thrombotic complications, and the role of prophylactic and therapeutic anticoagulation in patients with COVID-19. While existing evidence is limited in quality, COVID-19 appears to increase micro-and macro-vascular thrombosis rates in hospitalized and critically ill patients, which may contribute to the burden of disease. D-dimer can be used for risk stratification of hospitalized patients, but its role to guide anticoagulation therapy remains unclear. Evidence of higher quality is needed to address the role of therapeutic anticoagulation or high-intensity venous thromboembolism prophylaxis in COVID-19 patients. TAKE-HOME POINTS., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU)., Methods: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations., Results: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations., Conclusion: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions., Methods: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost., Results: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively ( P  = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE ( P  = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [ P  < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [ P  = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE., Conclusion: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost., Competing Interests: Yen-I Chen, Avijit Chatterjee, Ian Gan, and Fergal Donnellan are consultants for Boston Scientific. Alan Barkun is a consultant for Pendopharm Inc., Boston Scientific Inc., Olympus Inc., Cook Inc., and ATGen Inc. Clarence Wong is a consultant for Boston Scientific and Medtronic Medical. The remaining authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted., Competing Interests: E.B.-C. reports grants from Bayer and Roche, outside the submitted work. I.M.B. received a stipend for administrative work, Trillium Gift of Life ODO 2014-2019, Motivational Speaker for Gaia Insight. M.O.M. receives salary from the Trillium Gift of Life Network of Ontario for her work as a hospital donation physician. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Dr. Alhazzani is the Chair of the Guidelines Chapter for the Saudi Critical Care Society and is the chair of the guidelines in intensive care, development and evaluation (GUIDE) Group, McMaster University Canada. Dr. Antonelli received funding from GE, Toray-Estor, Baxter, Pfizer, Orion, Maquet, and Fisher and Paykel; he was on the board of Baxter and Pfizer, and is a member of the executive committee and past president of Società Italiana di Anestesia Rianimazione e Terapia Intensiva (SIAARTI). Dr. French contributed to the ANZICS Guidelines and the National COVID-19 Guidelines. Dr. Machado is a member of the Executive Committee for the Basics Study (for which Baxter provided the drugs and logistics) and AMIB. Dr. McIntyre is a member of the Canadian Critical Care Society and serves on the Surviving Sepsis Campaign Steering Committee. Dr. Ostermann is a council member of the Intensive Care Society UK and member of the Renal Association UK and World Sepsis Alliance. Dr. Prescott is a member of the ATS Critical Care Program Committee. Dr. Simpson is the president-elect and Chair of CHEST, is a member of the board of directors and medical director of Sepsis Alliance, and Chair of the Sepsis Institute Advisory Board. Dr. Wiersinga is a member of ISF, ESCIMID, and SWAB. Dr. Angus received funding from Ferring Pharmaceuticals, Inc and ALung Technologies, Inc. Dr. Beale provides consultancy services for Philips Healthcare with his time billed by his institution. Dr. Beilman is the president of the Surgical Infection Society. Dr. Belley-Cote received grants from Roche and Bayer and is a panel member on the Saudi Critical Care Society COVID-19 Thrombosis Guidelines. Dr. Cecconi is a consultant for Edwards Lifesciences, Cheetah Medical, and Directed Systems and is President of the European Society of Intensive Care Medicine. Dr. Coz is a board member of the American College of Chest Physicians. Dr. De Waele consulted for Accelerate, Bayer, Grifols, Pfizer, and MSD with all honoraria paid to Ghent University; he is a Senior Clinical Investigator with the Research Foundation Flanders. Dr. Dellinger serves as an expert witness on occasional medical legal case reviews. Dr. Doi is a member of the Japanese Society of Intensive Care Medicine. Dr. Du is a member of the Chinese Society of Critical Care Medicine and the Chinese College of Intensive Care Medicine. Dr. Ferrer received funding from Grifols, MSD, Pfizer, Shionogi, Toray, Jafron, and Cytosorbents; he is a member of SEMICYUC. Dr. Gomersall is a member of an educational subgroup of the International Forum of Acute Care Trialists. Dr. Hodgson is a member of the Australian National Health and Medical Research Council guidelines (COVID-19) and leading funded trials in early rehabilitation and ECMO. Dr. Møller contributed to guideline work for DASAIM, SSAI, GUIDE, and ESA. Dr. Iwashyna is a member of the ATS, the NIH, and an informal (unincorporated) organization called the Critical and Acute Illness Recovery Organization. Dr. Jacob co-directs the African Research Collaboration on Sepsis (ARCS, funded by UK National Institute for Health Research, sponsored by Liverpool School of Tropical Medicine), he is Secretary General for the African Sepsis Alliance, and is a technical expert for the World Health Organization panels. Dr. Kleinpell is a board member of the World Federation of Intensive and Critical Care, American Nurses Credentialing Center, and the Tennessee Nurses Association Political Action Committee. Dr. Klompas received funding from Up-to-Date; he is a member of the guidelines committees of the Infectious Disease Society of America (IDSA) and Society of Healthcare Epidemiologists of America (SHEA). Dr. Koh is a member of The Korean Society of Critical Care Medicine, The Korean Academy of Tuberculosis and Respiratory Diseases, The Korean Society of Medical Ethics, and the Asia Ventilation Forum. Dr. Kumar served as an expert witness regarding a lethal dose of narcotics. Dr. Kwizera is president of the Intensive Care Society of Uganda and PRO for the Association of Anesthesiologists of Uganda. Dr. Lobo received funding from Pfizer, MSD, Edwards, and Nestle; she is the principal investigator in new antibiotics research led by CROs/industry; she is a member of the AMIB Executive Board and was elected president for 2020-2021. Dr. McGloughlin is a member of ANZICS (Australian New Zealand Intensive Care Society). Dr. Mehta participated in two non-interventional studies by ISCCM-Hermes and Indicaps. Dr. Mer has been an invited speaker for educational talks in industry-sponsored symposia for which honoraria was received; he is the current Vice President of the Southern African Society of Thrombosis and Haemostasis (SASTH), and is involved in annual congress organization; he is an invited author of the Global guidelines for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Dr. Nunnally is the treasurer of SOCCA, committee member of ASA, NYSSA, IARS, AUA, and SAAAPM and serves on the American College of Critical Care Medicine Board of Regents. Dr. Oczkowski is a member of the European Respiratory Society, and contributed to the High Flow Nasal Cannula Guidelines, the Non-Invasive Ventilation in COPD Guidelines. Dr. Osborn received funding from Viven Inc, Inflammatrix, Beckman, and the Foundation for Barnes Jewish Hospital; she is on the advisory board for Beckman, Inflammatix, and Viven; she is a member of the American College of Emergency Physicians, American College of Chest Physicians, American Medical Association, Society of Academic Emergency Medicine, and American Academy of Emergency Physicians; she served as an expert witness in a case related to viral as compared to bacterial sepsis. Dr. Papathanassoglou is a member of the World Federation of Critical Care Nurses (Editor of Journal) and the Canadian Association of Critical Care Nurses. Dr. Perner received a research grant from Pfizer Denmark. Dr. Puskarich is the co-inventor of a patent to assess L0carnitine drug responsiveness in sepsis (USPO 10330685); he is a member of the Society for Academic Emergency Medicine, American College of Emergency Physicians (ACEP); he was invited to a recently gathered ACEP early sepsis treatment policy task force asked to develop specialty recommendations for early sepsis treatment. Dr. Roberts received funding from MSD, The Medicines Company, Cardeas Pharma, Biomerieux, QPEX, Cipla, and Pfizer; he consulted for MSD, QPEX, Discuva Ltd, Accelerate Diagnostics, Bayer, Biomerieux, UptoDate, and Australian Therapeutic Guidelines; he is a member of the Society of Hospital Pharmacists of Australia Leadership Committees for Critical Care and Infectious Diseases and the Lead of Sepsis Working group for the International Society of Anti-infective Chemotherapy. Dr. Schweickert is a paid consultant to the American College of Physicians (last performed in Spring, 2019). Dr. Seckel volunteers for AACN and is a paid consultant to revise online Critical Care Orientation. Dr. Sevransky received funding from the Marcus Foundation- PI VICTAS Trial and serves on the American College of Critical Care Medicine Board of Regents. Dr. Welte received funding from Astellas, AstraZeneca, Boehringer, Basilea, Bayer, Berlin-Chemie, Grifols, Infectopharm, Mundipharma, MSD, Novartis, Pfizer, DFG, EU, BMBF, and Insmed; he is on the advisory board for AstraZeneca, Boehringer, Bayer, Gilead, GSK, Insmed, Novartis, Pfizer, Roche; he is a member of the European Respiratory Society, German Society of Pneumology, and Paul Ehrlich Gesellschaft. Dr. Zimmerman is a member of the ACP, AACP, and WFPICCS. Dr. Levy is a legal consultant for a few cases involving sepsis and serves as co-chair of the Surviving Sepsis Campaign Steering Committee. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: The cuff leak test (CLT) is used to assess laryngeal edema prior to extubation. There is limited evidence for its diagnostic accuracy and conflicting guidelines surrounding its use in critically ill patients who do not have risk factors for laryngeal edema. The primary study aim was to describe intensivists' beliefs, attitudes, and practice regarding the use of the CLT., Methods: A 13-item survey was developed, pilot-tested, and subjected to clinical sensibility testing. The survey was distributed electronically through MetaClinician®. Descriptive statistics and multivariable regression analysis were performed to examine associations between participant demographics and survey responses., Results: 1184 practicing intensivists from 17 countries in North and South America, Europe, Oceania, and Asia participated. The majority (59%) of respondents reported rarely or never perform the CLT prior to extubating patients not at high risk of laryngeal edema, which correlated with 54% of respondents reporting they believed a failed CLT did not predict reintubation. Intensivists from the Middle East were 2.4 times more likely to request a CLT compared to those from North America. Intensivists with base training in medicine or emergency medicine were more likely to request a CLT prior to extubation compared to those with base training in anesthesiology., Conclusion: Use of the CLT prior to extubating patients not at high risk of laryngeal edema in the intensive care unit is highly variable. Practice appears to be influenced by country of practice and base specialty training., (© 2021 Acta Anaesthesiologica Scandinavica Foundation.)

Objective: To examine the association between plasma levels of the soluble urokinase plasminogen activator receptor (suPAR) and the incidence of severe complications of COVID-19., Methods: 403 RT-PCR-confirmed COVID-19 patients were recruited and prospectively followed-up at a major hospital in the United Arab Emirates. The primary endpoint was time from admission until the development of a composite outcome, including acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, or death from any cause. Patients discharged alive were considered as competing events to the primary outcome. Competing risk regression was used to quantify the association between suPAR and the incidence of the primary outcome., Results: 6.2% of patients experienced ARDS or ICU admission, but none died. Taking into account competing risk, the incidence of the primary outcome was 11.5% (95% confidence interval [CI], 6.7-16.3) in patients with suPAR levels >3.91 ng/mL compared to 2.9% (95% CI, 0.4-5.5) in those with suPAR ≤3.91 ng/mL. Also, an increase by 1 ng/mL in baseline suPAR resulted in a 58% rise in the hazard of developing the primary outcome (hazard ratio 1.6, 95% CI, 1.2-2.1, p = 0.003)., Conclusion: suPAR has an excellent prognostic utility in predicting severe complications in hospitalised COVID-19 patients., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU., Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility., Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning., Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available., Competing Interests: Dr. Evans has disclosed that she is a PI on a multi-center observational cohort study of hospitalized patients with severe acute respiratory infection, funded by the CDC Foundation. Drs. Prescott, Chertow, and Mammen disclosed government work. Dr. Fan received funding from Lung Technologies, MC3 Cardiopulmonary, and Fresenius Medical Care. Dr. Derde’s institution received funding from ZonMw (Den Haag, Europe) grant number 10150062010003, the Canadian Institutes of Health Research (CIHR), and from Rapid European COVID-19 Emergency Research response (RECOVER) (Europe, H2020) grant agreement No 101003589, and her institution has agreements with Faron (interferon), SOBI (anakinra), and Abbvie (lopinavir/r) to supply drugs for the above-funded studies. Dr. Du’s institution received funding from the Ministry of Science and Technology for a COVID-19–related study (NCT04244591). Dr. Crowther received funding from Servier Canada, Asahi Kasei, Precision Biologicals, Hemostasis Reference Laboratory, Pfizer, CSL Behring, Diagnostica Stago, and he disclosed that he undertakes significant amounts of both medical malpractice and product work in the general areas of hematology and thromboembolism. Dr. Belley-Cote received funding from CIHR, Roche, and Bayer as a principal investigator for the ACT trial that evaluates hydroxychloroquine, interferon beta, colchicine, aspirin, and rivaroxaban in patients with COVID-19. Dr. Zarychanski received operating grants from CIHR, LifeArc Foundation, Thistledown Foundation, and Research Manitoba for grants related to anticoagulation in COVID-19. Dr. McGreer’s institution received funding from Appili Therapeutics. Dr. Hayden disclosed he is a nonpaid consultant for multiple companies involved in developing COVID-19 countermeasures (Arcturus, Cidara, Gilead, GSK, resTORbio, Regeneron, SAB Biotherapeutics, Takeda, Vir), and he is a DSMB member for CytoDyn. Dr. Martin received funding from serving on a clinical trial data monitoring board. Dr. Antonelli received funding from consulting for Intersurgical and ESTOR. Dr. Waleed Alhazzani is the principal investigator on awake proning trial in COVID-19 COVI-PRONE. Dr. Yaseen Arabi is the principal investigator on a clinical trial for lopinavir/ritonavir and interferon in Middle East respiratory syndrome (MERS) and he was a nonpaid consultant on antiviral active for MERS-coronavirus (CoV) for Gilead Sciences and SAB Biotherapeutics. He is an investigator on REMAP-CAP trial and is a Board Members of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). He is a co-investigator on the REMAP-CAP trial and on an awake proning trial in COVID-19 (COVI-PRONE). Dr. Maurizio Cecconi declared consultancy work with Edwards Lifesciences, Directed Systems, and Cheetah Medical: Dr. Lennie Derde is an investigator on REMAP-CAP trial, the NVIC (Dutch National ICU society) chair of Taskforce Infectious Diseases (standing committee), member of ESICM Coronavirus Taskforce (started with this outbreak), and chair of the ESICM Clinical Training Committee; all are unpaid positions. Dr. Laura Evans is the team leader for the critical care section of the NIH COVID-19 management guideline. Dr. Eddy Fan declared receiving consultancy fees from ALung Technologies and MC3 Cardiopulmonary. Dr. Frederick Hayden is a noncompensated consultant to Gilead Sciences, Regeneron, Cidara, Fujifilm, Ridgeback, Merck, Roche/Genentech, GSK, Vir, resTORbio, and SAB Biotherapeutics, and he is a DSMB member for CytoDyn therapeutic clinical trial: Dr. Manoj J. Mammen is an investigator for the U.S. NIH PASSive Immunity Trial for Our Nation (PassItOn) trial: Dr. Greg Martin is a member of the NIH COVID-19 treatment guidelines, principal investigator for COVID-19 diagnostic testing (U.S. NIH RADx program) and has served as a research consultant to Genentech, Grifols, Regeneron and Siemens. Dr. Massimo Antonelli declared consultancy with Toray/Estor and Fisher and Pykel and research grant from GE. Dr. Flavia Machado is member of the executive committee for the CODEX study. Dr. Sheila Nainan Myatra is on the steering committee of the COVID Steroid 2 Trial (ClinicalTrials.gov Identifier: NCT04509973) and the HydrOxychloroquine Prophylaxis Evaluation (HOPE) Trial (CTRI registration No.CTRI/2020/05/025067). Dr Naomi Hammond is on the steering committee of the COVID Steroid 2 Trial (ClinicalTrials.gov Identifier: NCT04509973) and the HydrOxychloroquine Prophylaxis Evaluation (HOPE) Trial (CTRI registration No.CTRI/2020/05/025067). Dr. Emilie Belley-Cote reports grants from Bayer, grants from Roche outside the submitted work. She is a principal investigator for the ACT trial: The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: Fever is frequently encountered in ICU. It is unclear if targeted temperature control is beneficial in critically ill patients with suspected or confirmed infection. We conducted a systemic review and meta-analysis to answer this question., Methods: We systematically reviewed major databases before January 2020 to identify randomized controlled trials (RCTs) that compared antipyretic with placebo for temperature control in non-neurocritical ill adult patients with suspected or confirmed infection. Outcomes of interest were 28-day mortality, temperature level, hospital mortality, length of stay, shock reversal, and patient comfort., Result: 13 RCTs enrolling 1963 patients were included. No difference in 28-day mortality between antipyretic compared with placebo (risk ratio [RR] 1.03; 95% CI 0.79-1.35). Lower temperature levels were achieved in the antipyretic group (MD [mean difference] -0.41; 95% CI -0.66 to -0.16). Antipyretic use did not affect the risk of hospital mortality (RR 0.97; 95% CI 0.73-1.30), ICU length of stay (MD -0.07; 95% CI -0.70 to 0.56), or shock reversal (RR 1.11; 95% CI 0.76-1.62)., Conclusion: Antipyretic therapy effectively reduces temperature in non-neurocritical ill patients but does not reduce mortality or impact other outcomes., Competing Interests: Declaration of Competing Interest No other competing interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Populations such as healthcare workers (HCW) that are unable to practice physical distancing are at high risk of acquiring Coronavirus disease-2019 (COVID-19). In these cases pharmacological prophylaxis would be a solution to reduce severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) transmission. Hydroxychloroquine has in vitro antiviral properties against SARS CoV-2. We therefore sought to determine the efficacy and safety of hydroxychloroquine as prophylaxis for COVID-19., Methods and Findings: We electronically searched EMBASE, MEDLINE, the Cochrane COVID-19 Register of Controlled Trials, Epistemonikos COVID-19, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to September 28th, 2020 for randomized controlled trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes with the corresponding 95% confidence intervals (CIs) using a random-effect model. We identified four RCTs (n = 4921) that met our eligibility criteria. The use of hydroxychloroquine, compared to placebo, did not reduce the risks of developing COVID-19 (RR 0.82, 95% CI 0.65 to 1.04, moderate certainty), hospitalization (RR 0.72, 95% CI 0.34 to 1.50, moderate certainty), or mortality (RR 3.26, 95% CI 0.13 to 79.74, low certainty), however, hydroxychloroquine use increased the risk of adverse events (RR 2.76, 95% CI 1.38 to 5.55, moderate certainty)., Conclusion: Although pharmacologic prophylaxis is an attractive preventive strategy against COVID-19, the current body of evidence failed to show clinical benefit for prophylactic hydroxychloroquine and showed a higher risk of adverse events when compared to placebo or no prophylaxis., Competing Interests: The authors have declared that no competing interests exist.

Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed., Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations., Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy., Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

Background: The prevalence of traditional risk factors such as diabetes mellitus (DM) and obesity are increasing in patients with acute coronary syndrome (ACS). Furthermore, outcomes after ACS are worse in patients with DM. The high prevalence of DM and an early age at onset of ACS have been described in prior publications from the Gulf Coast Database., Aims: We aimed to define the effect of DM on total mortality following ACS presentation at 30-days and 1 year based on the Gulf COAST registry database., Methods: The Gulf COAST registry is a prospective, multinational, longitudinal, observational cohort study conducted among Gulf citizens admitted with a diagnosis of ACS. The outcomes among patients with DM following ACS were stratified into 2 groups based on their DM status. Cumulative survival stratified by groups and subgroup categories was assessed by the Kaplan-Meier method., Results: Of 3,576 ACS patients, 2,730 (76.3%) presented with non ST-segment elevation myocardial infarction (NSTEMI) and 846 (23.6%) with STEMI. Overall, 1906 patients (53.3%) had DM. A significantly higher in-hospital (4.8%), 30-day (6.7%) and 1-year (13.7%) mortality were observed in patients with DM compared with those without DM. The Kaplan-Meier survival curve showed significant differences in survival of ACS patients with or without DM, with a short period of time-to-event for DM patients with STEMI (30-days) and the longest (1-year) for NSTEMI patients without DM., Conclusion: DM patients presenting with ACS-STEMI have poor short-term outcomes while DMNSTEMI patients have poor long-term outcomes. This highlights the need for strategies to evaluate DM control and integration of care to control vascular risk among this high-risk population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure., Methods: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence., Results: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain., Conclusions: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Purpose: Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients., Methods: Patients admitted to participating intensive care units during the one-month enrolment period were eligible. We excluded cardiac surgical patients and patients who were admitted and either died or were discharged within 12 hr. In enrolled patients, we measured high-sensitivity cardiac troponin I (hs-cTnI) and obtained electrocardiograms to ascertain the incidence of myocardial infarction (MI) and isolated troponin elevation. Our feasibility objectives were to measure recruitment rate, the proportion of patients who consented under a deferred consent model, and time required for data collection and study procedures., Results: Over a four-week enrolment period, 280 patients were enrolled using a deferred consent model. We obtained subsequent consent from 81% of patients. Study procedures and data collection required 1.7 hr per participant. Overall, 86 (38%) suffered a MI, 23 (10%) had an isolated hs-cTnI elevation, and 117 (52%) had no hs-cTnI elevation. The crude hospital mortality rate was 10% without an hs-cTnI elevation, 29% with an isolated hs-cTnl elevation (relative risk [RR]) 2.2; 95% confidence interval [CI], 1.0 to 6.0) and 29% with an MI (RR, 2.6; 95% CI, 1.4 to 5.1)., Conclusion: Myocardial injury with elevated hs-cTnI concentrations and MIs occur frequently during critical illness. This pilot study has established the feasibility of conducting a large-scale investigation addressing this issue.