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Objective: Unusual clinical course Background: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is associated with high morbidity and mortality. Recently, MRSA testing by nasal swab has been utilized to "exclude" pneumonia caused by MRSA, given its high negative-predictive value (NPV). We present, however, a case of MRSA pneumonia diagnosed by endotracheal aspirate culture (EAC) in a patient with a negative MRSA nasal swab. Case Report: A 58-year-old woman presented with septic shock and respiratory failure. Chest X-ray (CXR) on admission was unrevealing; however, computed tomography (CT) revealed multifocal pneumonia. Intensive Care Unit (ICU)- level care was required for mechanical ventilation and vasopressors. She initially improved with treatment of community-acquired pneumonia (CAP) and was extubated on hospital day 6; however, she then developed a fever, tachycardia, and respiratory distress necessitating re-intubation later that day. Repeat CXR demonstrated a new left lower lobe infiltrate. Blood cultures were drawn and vancomycin and cefepime were started to cover for ventilator-associated pathogens. An EAC and nasal swab were collected to test for MRSA. The next day (day 7), the MRSA nasal swab returned negative, and vancomycin was discontinued. Our patient continued to experience fevers, worsening leukocytosis, and ongoing vasopressor need. On hospital day 9, the EAC results were obtained, and were positive for MRSA. Vancomycin was restarted and our patient recovered. Conclusions: Negative MRSA nasal screening may be considered grounds to de-escalate empiric MRSA antibiotics if MRSA prevalence is low. However, in critically ill patients with high risk and suspicion for MRSA pneumonia, discontinuing empiric MRSA coverage should be done with caution or clinicians should wait until respiratory culture results are obtained before de-escalating antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: With decades of declining ICU mortality, we hypothesized that the outcomes and distribution of diseases cared for in the ICU have changed and we aimed to further characterize them. Study Design and Methods: A retrospective cohort analysis of 287,154 nonsurgical-critically ill adults, from 237 U.S. ICUs, using the manually abstracted Cerner APACHE Outcomes database from 2008 to 2016 was performed. Surgical patients, rare admission diagnoses (<100 occurrences), and low volume hospitals (<100 total admissions) were excluded. Diagnoses were distributed into mutually exclusive organ system/disease-based categories based on admission diagnosis. Multi-level mixed-effects negative binomial regression was used to assess temporal trends in admission, in-hospital mortality, and length of stay (LOS). Results: The number of ICU admissions remained unchanged (IRR 0.99, 0.98-1.003) while certain organ system/disease groups increased (toxicology [25%], hematologic/oncologic [55%] while others decreased (gastrointestinal [31%], pulmonary [24%]). Overall risk-adjusted in-hospital mortality was unchanged (IRR 0.98, 0.96-1.0004). Risk-adjusted ICU LOS (Estimate -0.06 days/year, -0.07 to-0.04) decreased. Risk-adjusted mortality varied significantly by disease. Conclusion: Risk-adjusted ICU mortality rate did not change over the study period, but there was evidence of shifting disease burden across the critical care population. Our data provides useful information regarding future ICU personnel and resource needs. [ABSTRACT FROM AUTHOR]

Background: Pancreatitis accounts for more than $2.5 billion of healthcare costs and remains the most common gastrointestinal (GI) admission. Few contemporary studies have assessed temporal trends of incidence, complications, management, and outcomes for acute pancreatitis in hospitalized patients at the national level. Methods: We used data from one of the largest hospital-based databases available in the United States, the Healthcare Cost and Utilization Project's (HCUP) State Inpatient Database, from 10 states between 2008 and 2015. We included patients with a diagnosis of acute pancreatitis (ICD-9 CM 577.0). Patient- and hospital-level data were used to estimate incidence and inpatient mortality rates. Results: From 80,736,256 hospitalizations, 929,914 (1.15%) cases of acute pancreatitis were identified, 186,226 (20.2%) of which were caused by gallbladder disease). The median age was 53 years (interquartile range [IQR], 41-67) and 50.8% were men. In-hospital mortality was 2.5% and crude mortality rates declined from 2.9% to 2.0% over the study period. Admission year remained significant after adjusting for patient demographics and comorbidities (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.89-0.90; p < 0.001). Gallbladder disease was associated with decreased odds of mortality (OR, 0.60; 95% CI, 0.57-0.62). Median length of stay was four days (IQR, 2-7) and decreased over time. The rates of surgical and endoscopic interventions were highest in 2011 (peak incidence of 16.1% and 9.5%, respectively) and have been decreasing since. Surgical providers were, on average, more likely than medical providers to perform surgery in both those with and without gallbladder disease etiology (gallbladder disease OR, 7.11; 95% CI, 5.46-9.25; non-gallbladder disease OR, 20.50; 95% CI, 16.81-25.01), endoscopy (gallbladder disease OR, 1.22; 95% CI, 0.87-1.72; non-gallbladder disease OR, 1.60; 95% CI, 1.18-2.16), or both (gallbladder disease OR, 7.00; 95% CI, 5.22-9.37; non-gallbladder disease OR, 8.85; 95% CI, 5.61-13.96). Conclusions: The incidence of pancreatitis, from 2008 to 2015, has increased whereas inpatient mortality (i.e., case fatality) has decreased. Understanding temporal trends in outcomes and management along with provider, hospital, and regional variation can better identify areas for future research and collaboration in managing these patients. [ABSTRACT FROM AUTHOR]

The recently discovered Omicron variant of SARS-CoV-2 has rapidly burst into the public and scientific eye, being detected in more than 26 countries around the world. Given its more than 50 mutations, there is widespread concern about its public health impact, leading theWorld Health Organization to designate it a variant of concern. This Commentary provides a summary of current knowledge and unknowns about this viral variant as of December 2, 2021 and summarizes the key questions that need to be rapidly answered. [ABSTRACT FROM AUTHOR]

Background: Despite past and ongoing efforts to achieve health equity in the USA, racial and ethnic disparities persist and appear to be exacerbated by COVID-19. Objective: Evaluate neighborhood-level deprivation and English language proficiency effect on disproportionate outcomes seen in racial and ethnic minorities diagnosed with COVID-19. Design: Retrospective cohort study Setting: Health records of 12 Midwest hospitals and 60 clinics in Minnesota between March 4, 2020, and August 19, 2020 Patients: Polymerase chain reaction–positive COVID-19 patients Exposures: Area Deprivation Index (ADI) and primary language Main Measures: The primary outcome was COVID-19 severity, using hospitalization within 45 days of diagnosis as a marker of severity. Logistic and competing-risk regression models assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race, effects of ADI and primary language were measured using logistic regression. Results: A total of 5577 individuals infected with SARS-CoV-2 were included; 866 (n = 15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 vs. 40.4 years, p < 0.001) and more likely to be male (n = 425 [49.1%] vs. 2049 [43.5%], p = 0.002). Of those requiring hospitalization, 43.9% (n = 381), 19.9% (n = 172), 18.6% (n = 161), and 11.8% (n = 102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity: Hispanic patients (OR 3.8, 95% CI 2.72–5.30), Asians (OR 2.39, 95% CI 1.74–3.29), and Blacks (OR 1.50, 95% CI 1.15–1.94). ADI was not associated with hospitalization. Non-English-speaking (OR 1.91, 95% CI 1.51–2.43) significantly increased odds of hospital admission across and within minority groups. Conclusions: Minority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes. Non-English-speaking accounts for differences across and within minority populations. These results support the ongoing need to determine the mechanisms that contribute to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity among minority groups. [ABSTRACT FROM AUTHOR]

Purpose: Heterogeneity has been observed in outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19). Identification of clinical phenotypes may facilitate tailored therapy and improve outcomes. The purpose of this study is to identify specific clinical phenotypes across COVID-19 patients and compare admission characteristics and outcomes. Methods: This is a retrospective analysis of COVID-19 patients from March 7, 2020 to August 25, 2020 at 14 U.S. hospitals. Ensemble clustering was performed on 33 variables collected within 72 hours of admission. Principal component analysis was performed to visualize variable contributions to clustering. Multinomial regression models were fit to compare patient comorbidities across phenotypes. Multivariable models were fit to estimate associations between phenotype and in-hospital complications and clinical outcomes. Results: The database included 1,022 hospitalized patients with COVID-19. Three clinical phenotypes were identified (I, II, III), with 236 [23.1%] patients in phenotype I, 613 [60%] patients in phenotype II, and 173 [16.9%] patients in phenotype III. Patients with respiratory comorbidities were most commonly phenotype III (p = 0.002), while patients with hematologic, renal, and cardiac (all p<0.001) comorbidities were most commonly phenotype I. Adjusted odds of respiratory, renal, hepatic, metabolic (all p<0.001), and hematological (p = 0.02) complications were highest for phenotype I. Phenotypes I and II were associated with 7.30-fold (HR:7.30, 95% CI:(3.11–17.17), p<0.001) and 2.57-fold (HR:2.57, 95% CI:(1.10–6.00), p = 0.03) increases in hazard of death relative to phenotype III. Conclusion: We identified three clinical COVID-19 phenotypes, reflecting patient populations with different comorbidities, complications, and clinical outcomes. Future research is needed to determine the utility of these phenotypes in clinical practice and trial design. [ABSTRACT FROM AUTHOR]

Objectives: Physical and psychologic deficits after an ICU admission are associated with lower quality of life, higher mortality, and resource utilization. This study aimed to examine the prevalence and secular changes of functional status deterioration during hospitalization among nonsurgical critical illness survivors over the past decade.Design: We performed a retrospective longitudinal cohort analysis.Setting: Analysis performed using the Cerner Acute Physiology and Chronic Health Evaluation outcomes database which included manually abstracted data from 236 U.S. hospitals from 2008 to 2016.Patients: We included nonsurgical adult ICU patients who survived their hospitalization and had a functional status documented at ICU admission and hospital discharge. Physical functional status was categorized as fully independent, partially dependent, or fully dependent.Interventions: None.Measurements and Main Results: Functional status deterioration occurred in 38,116 patients (29.3%). During the past decade, functional status deterioration increased in each disease category, as well as overall (prevalence rate ratio, 1.15; 95% CI, 1.13-1.17; p < 0.001). Magnitude of functional status deterioration also increased over time (odds ratio, 1.03; 95% CI, 1.03-1.03; p < 0.001) with hematological, sepsis, neurologic, and pulmonary disease categories having the highest odds of severe functional status deterioration.Conclusions: Following nonsurgical critical illness, the prevalence of functional status deterioration and magnitude increased in a nationally representative cohort, despite efforts to reduce ICU dysfunction over the past decade. Identifying the prevalence of functional status deterioration and primary etiologies associated with functional status deterioration will elucidate vital areas for further research and targeted interventions. Reducing ICU debilitation for key disease processes may improve ICU survivor mortality, enhance quality of life, and decrease healthcare utilization. [ABSTRACT FROM AUTHOR]

Background: Chronic critical illness (CCI) is a new and increasing entity that accounts for substantial cost despite its low incidence. We hypothesized that patients with end-stage liver failure undergoing liver transplant would be at high risk for developing CCI. With limited liver donors it is essential to understand pre- and peritransplant predictors of CCI. Methods: To accomplish this we performed a retrospective cohort study at a large academic transplant center of all adult liver transplant patients from 2011 to 2017. We defined CCI as the need for mechanical ventilation for seven days or more post-transplant. Recipients who had re-transplantation during their index admission, acute rejection, or who died during transplant surgery were excluded. Logistic regression was performed using the Akaike information criterion (AIC) and the likelihood ratio test. Results: We identified 382 transplant recipients. Forty-five (11.8%) developed CCI. Univariable analysis identified 16 pre-transplant factors associated with post-transplant CCI. Subsequent multivariable logistic regression identified eight independent factors associated with CCI in liver transplant recipients including previous liver transplant, acute renal failure, frailty, lower albumin level, higher international normalized ratio, need for mechanical ventilation, and higher systolic pulmonary artery pressure. Pre-transplant factors associated with protection against CCI included higher Model for End-Stage Liver Disease (MELD) score. Conclusion: The incidence of CCI post-liver transplant is similar to the general population admitted to the intensive care unit. Pre-transplant factors associated with CCI can help identify at-risk patients, and furthermore, promote further research and interventions with the goal to decrease the incidence of CCI in the liver transplant recipients. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are a rare cause of prosthetic joint infections (PJI). However, the prevalence of NTM infections may be increasing with the rise of newer immunosuppressive medications such as biologics. In this case report, we describe a rare complication of immunosuppressive therapies and highlight the complexity of diagnosing and treating PJI due to NTM. The patient is a 79-year-old Caucasian male with a history of severe destructive rheumatoid arthritis on several immunosuppressive agents and right hip osteoarthritis s/p total hip arthroplasty 15 years previously with several complex revisions, presenting with several weeks of worsening right hip and abdominal pain. A right hip CT scan revealed periprosthetic fluid collections. Aspiration of three fluid pockets was AFB smear-positive and grew Mycobacterium avium-intracellulare. The patient was deemed a poor surgical candidate. He underwent a limited I&D and several months of antimycobacterial therapy but clinically deteriorated and opted for hospice care. PJI caused by NTM are rare and difficult to treat. The increased use of biologics and prosthetic joint replacements over the past several decades may increase the risk of PJI due to NTM. A high index of suspicion for NTM in immunosuppressed patients with PJI is needed. [ABSTRACT FROM AUTHOR]

Importance: The SARS-CoV-2 pandemic has overwhelmed hospital capacity, prioritizing the need to understand factors associated with type of discharge disposition. Objective: Characterization of disposition associated factors following SARS-CoV-2. Design: Retrospective study of SARS-CoV-2 positive patients from March 7th, 2020, to May 4th, 2022, requiring hospitalization. Setting: Midwest academic health-system. Participants: Patients above the age 18 years admitted with PCR + SARS-CoV-2. Intervention: None. Main outcomes: Discharge to home versus PAC (inpatient rehabilitation facility (IRF), skilled-nursing facility (SNF), long-term acute care (LTACH)), or died/hospice while hospitalized (DH). Results: We identified 62,279 SARS-CoV-2 PCR+ patients; 6,248 required hospitalizations, of whom 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died in hospital (DH). Patients discharged to PAC had a higher median age (75.7 years, IQR: 65.6–85.1) compared to those discharged home (57.0 years, IQR: 38.2–69.9), and had longer mean length of stay (LOS) 14.7 days, SD: 14.0) compared to discharge home (5.8 days, SD: 5.9). Older age (RRR:1.04, 95% CI:1.041–1.055), and higher Elixhauser comorbidity index [EI] (RRR:1.19, 95% CI:1.168–1.218) were associated with higher rate of discharge to PAC versus home. Older age (RRR:1.069, 95% CI:1.060–1.077) and higher EI (RRR:1.09, 95% CI:1.071–1.126) were associated with more frequent DH versus home. Blacks, Asians, and Hispanics were less likely to be discharged to PAC (RRR, 0.64 CI 0.47–0.88), (RRR 0.48 CI 0.34–0.67) and (RRR 0.586 CI 0.352–0.975). Having alpha variant was associated with less frequent PAC discharge versus home (RRR 0.589 CI 0.444–780). The relative risks for DH were lower with a higher platelet count 0.998 (CI 0.99–0.99) and albumin levels 0.342 (CI 0.26–0.45), and higher with increased CRP (RRR 1.006 CI 1.004–1.007) and D-Dimer (RRR 1.070 CI 1.039–1.101). Increased albumin had lower risk to PAC discharge (RRR 0.630 CI 0.497–0.798. An increase in D-Dimer (RRR1.033 CI 1.002–1.064) and CRP (RRR1.002 CI1.001–1.004) was associated with higher risk of PAC discharge. A breakthrough (BT) infection was associated with lower likelihood of DH and PAC. Conclusion: Older age, higher EI, CRP and D-Dimer are associated with PAC and DH discharges following hospitalization with COVID-19 infection. BT infection reduces the likelihood of being discharged to PAC and DH. [ABSTRACT FROM AUTHOR]

Influx of calcium through voltage-dependent channels regulates processes throughout the nervous system. Specifically, influx through L-type channels plays a variety of roles in early neuronal development and is commonlymodulated by G-protein-coupled receptors such as GABAB receptors. Of the four isoforms of L-type channels, only CaV1.2 and CaV1.3 are predominately expressed in the nervous system. Both isoforms are inhibited by the same pharmacological agents, so it has been difficult to determine the role of specific isoforms in physiological processes. In the present study, Western blot analysis and confocal microscopy were utilized to study developmental expression levels and patterns of CaV1.2 and CaV1.3 in the CA1 region of rat hippocampus. Steady-state expression of CaV1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of CaV1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against CaV1.2 and CaV1.3 demonstrated the highest intensity of labeling in the proximal dendrites at all ages studied (P1-72). Immunohistochemical studies on one-week-old hippocampi demonstrated significantly more colocalization of GABAB receptors with CaV1.2 than with CaV1.3, suggesting that modulation of L-type calcium current in early development is mediated through CaV1.2 channels. [ABSTRACT FROM AUTHOR]

Context: One fundamental way to honor patient autonomy is to establish and enact their wishes for end-of-life care. Limited research exists regarding adherence with code status.Objectives: This study aimed to characterize cardiopulmonary resuscitation (CPR) attempts discordant with documented code status at the time of death in the U.S. and to elucidate potential contributing factors.Methods: The Cerner Acute Physiology and Chronic Health Evaluation (APACHE) outcomes database, which includes 237 U.S. hospitals that collect manually abstracted data from all critical care patients, was queried for adults admitted to intensive care units with a documented code status at the time of death from January 2008 to December 2016. The primary outcome was discordant CPR at death. Multivariable logistic regression models were used to identify patient-level and hospital-level associated factors after adjustment for age, hospital, and illness severity (APACHE III score).Results: A total of 21,537 patients from 56 hospitals were included. Of patients with a do-not-resuscitate code status, 149 (0.8%) received CPR at death, and associated factors included black race, higher APACHE III score, or treatment in small or nonteaching hospitals. Of patients with a full code status, 203 (9.0%) did not receive CPR at death, and associated factors included higher APACHE III score, primary neurologic or trauma diagnosis, or admission in a more recent year.Conclusion: At the time of death, 1.6% of patients received or did not undergo CPR in a manner discordant with their documented code statuses. Race and institutional factors were associated with discordant resuscitation, and addressing these disparities may promote concordant end-of-life care in all patients. [ABSTRACT FROM AUTHOR]

Objective: To prospectively evaluate a logistic regression-based machine learning (ML) prognostic algorithm implemented in real-time as a clinical decision support (CDS) system for symptomatic persons under investigation (PUI) for Coronavirus disease 2019 (COVID-19) in the emergency department (ED). Methods: We developed in a 12-hospital system a model using training and validation followed by a real-time assessment. The LASSO guided feature selection included demographics, comorbidities, home medications, vital signs. We constructed a logistic regression-based ML algorithm to predict "severe" COVID-19, defined as patients requiring intensive care unit (ICU) admission, invasive mechanical ventilation, or died in or out-of-hospital. Training data included 1,469 adult patients who tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within 14 days of acute care. We performed: 1) temporal validation in 414 SARS-CoV-2 positive patients, 2) validation in a PUI set of 13,271 patients with symptomatic SARS-CoV-2 test during an acute care visit, and 3) real-time validation in 2,174 ED patients with PUI test or positive SARS-CoV-2 result. Subgroup analysis was conducted across race and gender to ensure equity in performance. Results: The algorithm performed well on pre-implementation validations for predicting COVID-19 severity: 1) the temporal validation had an area under the receiver operating characteristic (AUROC) of 0.87 (95%-CI: 0.83, 0.91); 2) validation in the PUI population had an AUROC of 0.82 (95%-CI: 0.81, 0.83). The ED CDS system performed well in real-time with an AUROC of 0.85 (95%-CI, 0.83, 0.87). Zero patients in the lowest quintile developed "severe" COVID-19. Patients in the highest quintile developed "severe" COVID-19 in 33.2% of cases. The models performed without significant differences between genders and among race/ethnicities (all p-values > 0.05). Conclusion: A logistic regression model-based ML-enabled CDS can be developed, validated, and implemented with high performance across multiple hospitals while being equitable and maintaining performance in real-time validation. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Implementation (Results) Conclusions Learning health systems (LHSs) iteratively generate evidence that can be implemented into practice to improve care and produce generalizable knowledge. Pragmatic clinical trials fit well within LHSs as they combine real‐world data and experiences with a degree of methodological rigor which supports generalizability.We established a pragmatic clinical trial unit (“RapidEval”) to support the development of an LHS. To further advance the field of LHS, we sought to further characterize the role of health information technology (HIT), including innovative solutions and challenges that occur, to improve LHS project delivery.During the period from December 2021 to February 2023, eight projects were selected out of 51 applications to the RapidEval program, of which five were implemented, one is currently in pilot testing, and two are in planning. We evaluated pre‐study planning, implementation, analysis, and study closure approaches across all RapidEval initiatives to summarize approaches across studies and identify key innovations and learnings by gathering data from study investigators, quality staff, and IT staff, as well as RapidEval staff and leadership.Implementation approaches spanned a range of HIT capabilities including interruptive alerts, clinical decision support integrated into order systems, patient navigators, embedded micro‐education, targeted outpatient hand‐off documentation, and patient communication. Study approaches include pre‐post with time‐concordant controls (1), randomized stepped‐wedge (1), cluster randomized across providers (1) and location (3), and simple patient level randomization (2).Study selection, design, deployment, data collection, and analysis required close collaboration between data analysts, informaticists, and the RapidEval team. [ABSTRACT FROM AUTHOR]

Background: Trials have shown non-inferiority of non-operative management (NOM) for appendicitis, although critically ill patients have been often excluded. The purpose of this study is to evaluate surgical versus NOM outcomes in critically ill patients with appendicitis by measuring mortality and hospital length of stay (LOS). Patients and Methods: The Healthcare Cost and Utilization Project's (HCUP) Database was utilized to analyze data from 10 states between 2008 and 2015. All patients with acute appendicitis by International Classification of Diseases, Ninth Revision (ICD-9) codes over the age of 18 were included. Negative binomial and logistic regression were used to determine the association of acute renal failure (ARF), cardiovascular failure (CVF), pulmonary failure (PF), and sepsis by treatment strategy (laparoscopic, open, both, or no surgery) on mortality and hospital LOS. Results: Among 464,123 patients, 67.5%, 23.3%, 8.2%, and 0.8% underwent laparoscopic, open, NOM, or both laparoscopic and open surgery, respectively. Patients who underwent surgery had 58% lower odds of mortality and 34% shorter hospital LOS compared with NOM patients. Patients with ARF, CVF, PF, and sepsis had 102%, 383%, 475%, and 666% higher odds of mortality and a 47%, 46%, 71%, and 163% longer hospital LOS, respectively, compared with patients without these diagnoses on admission. Conclusions: Critical illness on admission increases mortality and hospital LOS. Patients who underwent laparoscopic, and to a lesser extent, open appendectomy had improved mortality compared with those who did not undergo surgery regardless of critical illness status. [ABSTRACT FROM AUTHOR]

Significant progress has been made in preventing severe COVID-19 disease through the development of vaccines. However, we still lack a validated baseline predictive biologic signature for the development of more severe disease in both outpatients and inpatients infected with SARS-CoV-2. The objective of this study was to develop and externally validate, via 5 international outpatient and inpatient trials and/or prospective cohort studies, a novel baseline proteomic signature, which predicts the development of moderate or severe (vs mild) disease in patients with COVID-19 from a proteomic analysis of 7000 + proteins. The secondary objective was exploratory, to identify (1) individual baseline protein levels and/or (2) protein level changes within the first 2 weeks of acute infection that are associated with the development of moderate/severe (vs mild) disease. For model development, samples collected from 2 randomized controlled trials were used. Plasma was isolated and the SomaLogic SomaScan platform was used to characterize protein levels for 7301 proteins of interest for all studies. We dichotomized 113 patients as having mild or moderate/severe COVID-19 disease. An elastic net approach was used to develop a predictive proteomic signature. For validation, we applied our signature to data from three independent prospective biomarker studies. We found 4110 proteins measured at baseline that significantly differed between patients with mild COVID-19 and those with moderate/severe COVID-19 after adjusting for multiple hypothesis testing. Baseline protein expression was associated with predicted disease severity with an error rate of 4.7% (AUC = 0.964). We also found that five proteins (Afamin, I-309, NKG2A, PRS57, LIPK) and patient age serve as a signature that separates patients with mild COVID-19 and patients with moderate/severe COVID-19 with an error rate of 1.77% (AUC = 0.9804). This panel was validated using data from 3 external studies with AUCs of 0.764 (Harvard University), 0.696 (University of Colorado), and 0.893 (Karolinska Institutet). In this study we developed and externally validated a baseline COVID-19 proteomic signature associated with disease severity for potential use in both outpatients and inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear. Methods Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted. Results The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P <.001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods. Conclusions SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time. Clinical Trial Registration. NCT04510194. [ABSTRACT FROM AUTHOR]

Sepsis-induced metabolic dysfunction is associated with mortality, but the signatures that differentiate variable clinical outcomes among survivors are unknown. Our aim was to determine the relationship between host metabolism and chronic critical illness (CCI) in patients with septic shock. We analyzed metabolomics data from mechanically ventilated patients with vasopressor-dependent septic shock from the placebo arm of a recently completed clinical trial. Baseline serum metabolites were measured by liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance. We conducted a time-to-event analysis censored at 28 days. Specifically, we determined the relationship between metabolites and time to extubation and freedom from vasopressors using a competing risk survival model, with death as a competing risk. We also compared metabolite concentrations between CCI patients, defined as intensive care unit level of care ≥ 14 days, and those with rapid recovery. Elevations in two acylcarnitines and four amino acids were related to the freedom from organ support (subdistributional hazard ratio < 1 and false discovery rate < 0.05). Proline, glycine, glutamine, and methionine were also elevated in patients who developed CCI. Our work highlights the need for further testing of metabolomics to identify patients at risk of CCI and to elucidate potential mechanisms that contribute to its etiology. [ABSTRACT FROM AUTHOR]

Some patients wish to forgo cardiopulmonary resuscitation (CPR) should they have a cardiac arrest. Young, S. Wordingham, J. Strand, Discordance of patient-reported and clinician-ordered resuscitation status in patients hospitalized with acute decompensated heart failure. [Extracted from the article]

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally. Both cigarette smoking and HIV have been identified as independent risk factors for COPD. We used data from the strategic timing of antiretroviral treatment (START) Pulmonary Substudy to quantify the impact of smoking on rate of lung function decline in HIV. Methods: We included START Pulmonary Substudy participants who contributed at least 2 good quality spirometry measures during the study. Slope of forced expiratory volume in 1 second (FEV1) was estimated using a repeated-measures model adjusted for the treatment group (immediate vs deferred treatment arm of START), age, sex, race, baseline COPD, and region. Results: Of 1026 START Pulmonary Substudy participants, 915 (89%) were included in this analysis. Median follow-up time was 3.9 years. Smokers and nonsmokers were similar in baseline age (median 36 years), but smokers were more likely to be white, male, and from Europe/Israel/Australia. Smokers had faster average FEV1 decline compared with nonsmokers [−38.3 mL/yr vs −25.1 mL/yr; difference of −13.2 mL/yr (95% confidence interval: −23.6 to −2.7); P = 0.013], were more likely to meet criteria for rapid FEV1 decline [7.2%–11.7% more likely (P = 0.09– P = 0.002), depending on the definition of rapid decline], and had borderline, but not statistically significant, higher incident COPD during follow-up (9.7% vs 5.8%, P = 0.06). Conclusions: Compared to nonsmokers, HIV-positive smokers experience faster decline in lung function. These results underscore the need for a better understanding of how to best support smoking cessation among HIV-positive populations. [ABSTRACT FROM AUTHOR]