Temporal Trends in Mortality of Critically Ill Patients with Sepsis in the United Kingdom, 1988-2019.

Rationale: Sepsis is a frequent cause of ICU admission and mortality. Objectives: To evaluate temporal trends in the presentation and outcomes of patients admitted to the ICU with sepsis and to assess the contribution of changing case mix to outcomes. Methods: We conducted a retrospective cohort study of patients admitted to 261 ICUs in the United Kingdom during 1988-1990 and 1996-2019 with nonsurgical sepsis. Measurements and Main Results: A total of 426,812 patients met study inclusion criteria. The patients had a median (interquartile range) age of 66 (53-75) years, and 55.6% were male. The most common sites of infection were respiratory (60.9%), genitourinary (11.5%), and gastrointestinal (10.3%). Compared with patients in 1988-1990, patients in 2017-2019 were older (median age, 66 vs. 63 yr), were less acutely ill (median Acute Physiology and Chronic Health Evaluation II acute physiology score, 14 vs. 20), and more often had genitourinary sepsis (13.4% vs. 2.0%). Hospital mortality decreased from 54.6% (95% confidence interval [CI], 51.0-58.1%) in 1988-1990 to 32.4% (95% CI, 32.1-32.7%) in 2017-2019, with an adjusted odds ratio of 0.64 (95% CI, 0.54-0.75). The adjusted absolute hospital mortality reduction from 1988-1990 to 2017-2019 was 8.8% (95% CI, 5.6-12.1). Thus, of the observed 22.2-percentage point reduction in hospital mortality, 13.4 percentage points (60% of total reduction) were explained by case mix changes, whereas 8.8 percentage points (40% of total reduction) were not explained by measured factors and may be a result of improvements in ICU management. Conclusions: Over a 30-year period, mortality for ICU admissions with sepsis decreased substantially. Although changes in case mix accounted for the majority of observed mortality reduction, there was an 8.8-percentage point reduction in mortality not explained by case mix.

Atrial Fibrillation Occurring During Acute Hospitalization: A Scientific Statement From the American Heart Association.

Acute atrial fibrillation is defined as atrial fibrillation detected in the setting of acute care or acute illness; atrial fibrillation may be detected or managed for the first time during acute hospitalization for another condition. Atrial fibrillation after cardiothoracic surgery is a distinct type of acute atrial fibrillation. Acute atrial fibrillation is associated with high risk of long-term atrial fibrillation recurrence, warranting clinical attention during acute hospitalization and over long-term follow-up. A framework of substrates and triggers can be useful for evaluating and managing acute atrial fibrillation. Acute management requires a multipronged approach with interdisciplinary care collaboration, tailoring treatments to the patient's underlying substrate and acute condition. Key components of acute management include identification and treatment of triggers, selection and implementation of rate/rhythm control, and management of anticoagulation. Acute rate or rhythm control strategy should be individualized with consideration of the patient's capacity to tolerate rapid rates or atrioventricular dyssynchrony, and the patient's ability to tolerate the risk of the therapeutic strategy. Given the high risks of atrial fibrillation recurrence in patients with acute atrial fibrillation, clinical follow-up and heart rhythm monitoring are warranted. Long-term management is guided by patient substrate, with implications for intensity of heart rhythm monitoring, anticoagulation, and considerations for rhythm management strategies. Overall management of acute atrial fibrillation addresses substrates and triggers. The 3As of acute management are acute triggers, atrial fibrillation rate/rhythm management, and anticoagulation. The 2As and 2Ms of long-term management include monitoring of heart rhythm and modification of lifestyle and risk factors, in addition to considerations for atrial fibrillation rate/rhythm management and anticoagulation. Several gaps in knowledge related to acute atrial fibrillation exist and warrant future research.

Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Association between the stress hyperglycemia ratio and 28-day all-cause mortality in critically ill patients with sepsis: a retrospective cohort study and predictive model establishment based on machine learning.

BACKGROUND: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. METHODS: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. RESULTS: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322). CONCLUSION: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis.

High-resolution plasma metabolomics and thiamine status in critically Ill adult patients.

INTRODUCTION: Thiamine (Vitamin B1) is an essential micronutrient and is classically considered a co-factor in energy metabolism. The association between thiamine status and whole-body metabolism in critical illness has not been studied. OBJECTIVES: To determine association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites and connected metabolic pathways using high resolution metabolomics (HRM) in critically ill patients. METHODS: Cross-sectional study performed at Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were critically ill adults with an expected length of intensive care unit stay longer than 48 h and receiving chronic furosemide therapy. A total of 76 participants were included. Mean age was 69 years (range 33-92 years); 65% were female. Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP was measured by HPLC and plasma HRM was performed using liquid chromatography/mass spectrometry. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies (MWAS). MWAS using the highest and lowest TPP concentration tertiles was performed as a secondary analysis. RESULTS: Specific metabolic pathways associated with whole blood TPP levels in regression and tertile analysis included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways. CONCLUSIONS: Plasma HRM revealed that thiamine status, determined by whole blood TPP concentrations, was significantly associated with metabolites and metabolic pathways related to metabolism of energy, carbohydrates, amino acids, lipids, and the gut microbiome in adult critically ill patients.

Insights from CTTACC: immune system reset by cellular therapies for chronic illness after trauma, infection, and burn.

BACKGROUND AIMS: In this paper, we present a review of several selected talks presented at the CTTACC conference (Cellular Therapies in Trauma and Critical Care) held in Scottsdale, AZ in May 2023. This conference review highlights the potential for cellular therapies to "reset" the dysregulated immune response and restore physiologic functions to normal. Improvements in medical care systems and technology have increasingly saved lives after major traumatic events. However, many of these patients have complicated post-traumatic sequelae, ranging from short-term multi-organ failure to chronic critical illness. METHODS/RESULTS: Patients with chronic critical illness have been found to have dysregulated immune responses. These abnormal and harmful immune responses persist for years after the initial insult and can potentially be mitigated by treatment with cellular therapies. CONCLUSIONS: The sessions emphasized the need for more research and clinical trials with cellular therapies for the treatment of a multitude of chronic illnesses: post-trauma, radiation injury, COVID-19, burns, traumatic brain injury (TBI) and other chronic infections.

Administration of Free Amino Acids Improves Exogenous Amino Acid Availability when Compared with Intact Protein in Critically Ill Patients: A Randomized Controlled Study.

BACKGROUND: Protein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may improve postprandial amino acid availability. OBJECTIVE: Our objective was to quantify the uptake of diet-derived phenylalanine after the enteral administration of intact protein compared with an equivalent amount of free amino acids in critically ill patients. METHODS: Sixteen patients who were mechanically ventilated in intensive care unit (ICU) at risk of malabsorption received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine after an overnight fast. Patients were randomly allocated to receive 20 g intrinsically L-[1-13C]-phenylalanine-labeled milk protein or an equivalent amount of amino acids labeled with free L-[1-13C]-phenylalanine via a nasogastric tube over a 2-h period. Protein digestion and amino acid absorption kinetics and whole-body protein net balance were assessed throughout a 6-h period. RESULTS: After enteral nutrient infusion, both plasma phenylalanine and leucine concentrations increased (P-time < 0.001), with a more rapid and greater rise after free amino acid compared with intact protein administration (P-time × treatment = 0.003). Diet-derived phenylalanine released into the circulation was 25% greater after free amino acids compared with intact protein administration [68.7% (confidence interval {CI}: 62.3, 75.1%) compared with 43.8% (CI: 32.4, 55.2%), respectively; P < 0.001]. Whole-body protein net balance became positive after nutrient administration (P-time < 0.001) and tended to be more positive after free amino acid in provision (P-time × treatment = 0.07). CONCLUSIONS: The administration of free amino acids as opposed to intact protein further increases postprandial plasma amino acid availability in critically ill patients, allowing more diet-derived phenylalanine to become available to peripheral tissues. This trial was registered at clinicaltrials.gov as NCT04791774.

A novel measure to summarize blood transfusion practice during critical illness.

BACKGROUND: Large-scale observational studies have summarized transfusion practice using traditional measures of central tendency (e.g., the mean hemoglobin concentration at the time of transfusion). However, the mean hemoglobin concentration fails to identify specific hemoglobin concentration thresholds that drive practice. In the following brief report, we propose a novel measure of "practice discontinuity" that identifies specific practice-defining hemoglobin thresholds. STUDY DESIGN AND METHODS: We used the PINC AI Database (2016-2022) to identify adult patients admitted to an intensive care unit with at least one hemoglobin concentration measurement. For each day that hemoglobin was measured, we identified whether the patient received a red blood cell transfusion using hospital charge codes. We defined the "practice discontinuity" measure as the hemoglobin concentration at which there was the largest increase in transfusion use going from a higher to an incrementally lower hemoglobin concentration. We also calculated the mean and median pretransfusion hemoglobin concentrations. RESULTS: We identified 1,298,367 patients and 4,905,839 patient-days for inclusion. RBC transfusion occurred in a total of 530,654 (10.8%) patient-days. The overall pre-transfusion mean and median hemoglobin concentrations were 8.4 and 8.0 g/dL, respectively. The practice discontinuity measure identified 7.0 g/dL as the hemoglobin concentration at which transfusion use increased the most, from 46.6% of patient-days at a concentration of 7.0 g/dL to 74.8% of patient-days at a concentration of 6.9 g/dL. DISCUSSION: We propose that future studies of red blood cell transfusion practice consider inclusion of the practice discontinuity measure to more fully summarize clinical practice.

Temporal trends in critical care utilization and outcomes in allogeneic hematopoietic stem cell transplant recipients.

Historically, the prognosis of allogeneic hematopoietic stem cell transplant (allo-HCT) recipients who require intensive care unit (ICU) admission has been poor. We aimed to describe the epidemiological trends of ICU utilization and outcomes in allo-HCT patients. We conducted a retrospective cohort study including adults (≥ 18) undergoing allo-HCT between 01/01/2005 and 31/12/2020 at Mayo Clinic, Rochester. Temporal trends in outcomes were assessed by robust linear regression modelling. Risk factors for hospital mortality were chosen a priori and assessed with multivariable logistic regression modelling. Of 1,249 subjects, there were 486 ICU admissions among 287 individuals. Although older patients underwent allo-HCT (1.64 [95% CI: 1.11 to 2.45] years per year; P = 0.025), there was no change in ICU utilization over time (P = 0.91). The ICU and hospital mortality rates were 19.2% (55/287) and 28.2% (81/287), respectively. There was a decline in ICU mortality (-0.38% [95% CI: -0.70 to -0.06%] per year; P = 0.035). The 1-year post-HCT mortality for those requiring ICU admission was 56.1% (161/287), with no significant difference over time, versus 15.8% (141/891, 71 missing) among those who did not. The frequency and duration of invasive mechanical ventilation (IMV) declined. In multivariable analyses, higher serum lactate, higher sequential organ failure assessment (SOFA) scores, acute respiratory distress (ARDS), and need for IMV were associated with greater odds of hospital mortality. Over time, rates of ICU utilization have remained stable, despite increasing patient age. Several trends suggest improvement in outcomes, notably lower ICU mortality and frequency of IMV. However, long-term survival remains unchanged. Further work is needed to improve long-term outcomes in this population.

Dual-Energy CT muscle fat fraction as a new imaging biomarker of body composition and survival predictor in critically ill patients.

OBJECTIVE: To analyze changes in the muscular fat fraction (FF) during immobilization at the intensive care unit (ICU) using dual-energy CT (DECT) and evaluate the predictive value of the DECT FF as a new imaging biomarker for morbidity and survival. METHODS: Immobilized ICU patients (n = 81, 43.2% female, 60.3 ± 12.7 years) were included, who received two dual-source DECT scans (CT1, CT2) within a minimum interval of 10 days between 11/2019 and 09/2022. The DECT FF was quantified for the posterior paraspinal muscle by two radiologists using material decomposition. The skeletal muscle index (SMI), muscle radiodensity attenuation (MRA), subcutaneous-/ visceral adipose tissue area (SAT, VAT), and waist circumference (WC) were assessed. Reasons for ICU admission, clinical scoring systems, therapeutic regimes, and in-hospital mortality were noted. Linear mixed models, Cox regression, and intraclass correlation coefficients were employed. RESULTS: Between CT1 and CT2 (median 21 days), the DECT FF increased (from 20.9% ± 12.0 to 27.0% ± 12.0, p = 0.001). The SMI decreased (35.7 cm2/m2 ± 8.8 to 31.1 cm2/m2 ± 7.6, p < 0.001) as did the MRA (29 HU ± 10 to 26 HU ± 11, p = 0.009). WC, SAT, and VAT did not change. In-hospital mortality was 61.5%. In multivariable analyses, only the change in DECT FF was associated with in-hospital mortality (hazard ratio (HR) 9.20 [1.78-47.71], p = 0.008), renal replacement therapy (HR 48.67 [9.18-258.09], p < 0.001), and tracheotomy at ICU (HR 37.22 [5.66-245.02], p < 0.001). Inter-observer reproducibility of DECT FF measurements was excellent (CT1: 0.98 [0.97; 0.99], CT2: 0.99 [0.96-0.99]). CONCLUSION: The DECT FF appears to be suitable for detecting increasing myosteatosis. It seems to have predictive value as a new imaging biomarker for ICU patients. CLINICAL RELEVANCE STATEMENT: The dual-energy CT muscular fat fraction appears to be a robust imaging biomarker to detect and monitor myosteatosis. It has potential for prognosticating, risk stratifying, and thereby guiding therapeutic nutritional regimes and physiotherapy in critically ill patients. KEY POINTS: The dual-energy CT muscular fat fraction detects increasing myosteatosis caused by immobilization. Change in dual-energy CT muscular fat fraction was a predictor of  in-hospital morbidity and mortality. Dual-energy CT muscular fat fraction had a predictive value superior to established CT body composition parameters.

Luminal Delivery of Pectin-Modified Oxygen Microbubbles Mitigates Rodent Experimental Intestinal Ischemia.

INTRODUCTION: Ischemic gut injury is common in the intensive care unit, impairs gut barrier function, and contributes to multiorgan dysfunction. One novel intervention to mitigate ischemic gut injury is the direct luminal delivery of oxygen microbubbles (OMB). Formulations of OMB can be modified to control the rate of oxygen delivery. This project examined whether luminal delivery of pectin-modified OMB (OMBp5) can reduce ischemic gut injury in a rodent model. METHODS: The OMBp5 formulation was adapted to improve delivery of oxygen along the length of small intestine. Adult Sprague-Dawley rats (n = 24) were randomly allocated to three groups: sham-surgery (SS), intestinal ischemia (II), and intestinal ischemia plus luminal delivery of OMBp5 (II + O). Ischemia-reperfusion injury was induced by superior mesenteric artery occlusion for 45 min followed by reperfusion for 30 min. Outcome data included macroscopic score of mucosal injury, the histological score of gut injury, and plasma biomarkers of intestinal injury. RESULTS: Macroscopic, microscopic data, and intestinal injury biomarker results demonstrated minimal intestinal damage in the SS group and constant damage in the II group. II + O group had a significantly improved macroscopic score throughout the gut mucosa (P = 0.04) than the II. The mean histological score of gut injury for the II + O group was significantly improved on the II group (P ≤ 0.01) in the proximal intestine only, within 30 cm of delivery. No differences were observed in plasma biomarkers of intestinal injury following OMBp5 treatment. CONCLUSIONS: This proof-of-concept study has demonstrated that luminal OMBp5 decreases ischemic injury to the proximal small intestine. There is a need to improve oxygen delivery over the full length of the intestine. These findings support further studies with clinically relevant end points, such as systemic inflammation and vital organ dysfunction.

Lincosamide monotherapy treatment of methicillin-resistant Staphylococcus aureus pneumonia in tropical Australia: a case series.

Existing recommended first-line antibiotic agents for MRSA pneumonia have several shortcomings. We reviewed 29 cases of community- and hospital-acquired MRSA pneumonia managed at our hospital. Lincosamide monotherapy was administered to 21/29 (72%) and was the predominant antibiotic regimen (> 50% course duration) in 19/29 (66%). Patients receiving lincosamide-predominant monotherapy were no more likely to die or require intensive care unit admission than patients receiving vancomycin-predominant monotherapy (5/19 (26%) versus 4/7 (57%), p = 0.19); 5/7 (71%) patients admitted to ICU and 4/5 (80%) bacteraemic patients received lincosamide-predominant monotherapy. MRSA pneumonia can be safely treated with lincosamide monotherapy if the isolate is susceptible.

Immune and inflammation features of severe and critical Omicron infected patients during Omicron wave in China.

OBJECTIVE: The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. METHOD: A cross-sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. RESULT: Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. CONCLUSION: This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

Association between antithrombotic therapy and mortality in patients hospitalized for COVID­19.

BACKGROUND: The prothrombotic state is a common abnormality in patients with coronavirus disease 2019 (COVID-19). However, there is controversy over the use of anticoagulants, especially oral anticoagulants (OAC) due to limited studies. We sought to evaluate the association between antithrombotic therapy on mortality and clinical outcomes in patients hospitalized for COVID-19 through propensity score matching (PSM) analysis. METHODS: A retrospective cohort study was performed to include adult patients with COVID-19 in a university hospital. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and acute kidney injury (AKI) during hospitalization. PSM was used as a powerful tool for matching patients' baseline characteristics. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated from the models. RESULTS: Of 4,881 COVID-19 patients during the study period, 690 (14.1%) patients received antithrombotic therapy and 4,191 (85.9%) patients were under no antithrombotic therapy. After adjustment with multivariate regression analysis, patients receiving OAC, compared with those who did not receive any antithrombotic therapy, had significantly lower odds for in-hospital mortality (aOR: 0.46. 95% CI: 0.24 to 0.87; P= 0.017). PSM analysis observed similar results (aOR: 0.35. 95% CI: 0.19 to 0.61; P< 0.001). Moreover, in critically ill patients who received mechanical ventilation, antithrombotic treatment (aOR: 0.54. 95% CI: 0.32 to 0.89; P= 0.022) was associated with reduced risk of mortality. CONCLUSIONS: The application OACs was associated with reduced hospital mortality and mechanical ventilation requirement in COVID-19 patients. Besides, antithrombotic treatment was associated with a reduction in in-hospital mortality among critically ill COVID-19 patients who required mechanical ventilation.

Successful Application of a Hemoperfusion Machine in Separated System CRRT: Evaluating Effectiveness and Safety in Critically Ill Patients With AKI in Resource-Limited Settings.

BACKGROUND: It is imperative to note that integrated system continuous renal replacement therapy (CRRT) necessitates a sophisticated and costly apparatus, potentially limiting its availability within resource-limited settings. The introduction of a separated system for continuous veno-venous hemofiltration (CVVH), characterized by uncomplicated setup procedures with a hemoperfusion machine, holds promise as a feasible alternative to CRRT for critically ill patients with acute kidney injury (AKI). METHODS: We aimed to retrospectively analyze the effectiveness and safety of separated CRRT applied from a hemoperfusion machine in critically ill patients with AKI during the January 2015 to December 2021 period. We also examine the in-hospital mortality rate and multivariate logistic regression analysis to uncover the factors that affect mortality. RESULTS: We included a total of 129 critically ill patients who received separated system CRRT. The SOFA score at CRRT initiation was 12.6 ± 3.8. The fluid accumulation at the day of CRRT initiation was 3900 mL (622-8172 mL) All patients received pre- and postdilution CVVH. The mean prescribed CRRT dose was 22.4 ± 3.1 mL/kg/h. We found no serious complications including circuit explosion and air embolism. The in-hospital mortality rate was 68.9%. High SOFA score and positive fluid accumulation at CRRT initiation serve as predictors of survival. CONCLUSIONS: Separated system CRRT using a hemoperfusion machine provides a simplified system to operate and is proven to be effective and safe in real-life practice, especially in resource-limited areas.

Predictors of New Onset Atrial Fibrillation Burden in the Critically Ill.

INTRODUCTION: Atrial fibrillation (AF) is common in the intensive care unit (ICU) setting and has been associated with adverse outcomes. In this context, there is increasing research interest in AF burden as a predictor of subsequent adverse events. However, the pathophysiology and drivers of AF burden in the ICU are poorly understood. This study sought to evaluate the predictors of AF burden in critical illness-associated new-onset AF (CI-NOAF). METHODS: Out of 7,030 admissions in a tertiary general ICU between December 2015 and September 2018, 309 patients developed CI-NOAF. AF burden was defined as the percentage of monitored time in AF, as extracted from hourly interpretations of continuous ECG monitoring. Low and high AF burden groups were defined relative to the median AF burden. Clinical, laboratory, and echocardiographic parameters were extracted, and multivariable modelling with binary logistic regression was performed to evaluate for independent associations with AF burden. RESULTS: The median AF burden was 7.0%. Factors associated with increased AF burden were age, dyslipidaemia, chronic kidney disease, increased creatinine, CHA2DS2-VASc score, ICU admission diagnosis category, amiodarone administration, and left atrial area (LAA). Factors associated with lower AF burden were previous alcohol excess, burden of ventilation, the use of inotropes/vasopressors, and beta blockers. On multivariate analysis, increased LAA, chronic kidney disease, and amiodarone use were independently associated with increased AF burden, whereas beta blocker use was associated with lower AF burden. CONCLUSION: Left atrial size and chronic cardiovascular comorbidities appear to be the primary drivers of CI-NOAF burden, whereas factors related to acute illness and critical care intervention paradoxically did not appear to be a substantial driver of arrhythmia burden. Further research is needed regarding drivers of AF and the efficacy of rhythm control intervention in this unique setting.

The role of lipid emulsions containing omega-3 fatty acids for medical and surgical critical care patients.

In critical illness the regulation of inflammation and oxidative stress can improve patient outcomes, and thus omega-3 polyunsaturated fatty acids (PUFAs) have been used as part of parenteral nutrition (PN) owing to their potential anti-inflammatory effects. The international lipids in PN Summit, encompassed discussions and the production of consensus guidelines concerning PN intravenous lipid emulsion (ILE) use in critical care. The Lipid Summit participants agreed that the inclusion of fish oil in ILEs is associated with meaningful clinical benefits without signals of harm, based on a strong biological rationale and current clinical evidence. Decisions concerning ILE choice should be made based on current evidence, thus addressing clinical requirements for guidance, particularly as further definitive evidence seems unlikely to occur. In addition, a future of individualized ICU care is envisioned, yielding better clinical outcomes. This approach will require the greater use of intelligent study designs incorporating the use of biomarkers of omega-3 derivatives, inflammatory-resolving processes, and/or muscle protein breakdown.