Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections

OBJECTIVES: Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI

Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity

IMPORTANCE: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients

Validation of Automated Data Abstraction for SCCM Discovery VIRUS COVID-19 Registry: Practical EHR Export Pathways (VIRUS-PEEP)

BACKGROUND: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. OBJECTIVE: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. MATERIALS AND METHODS: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen\u27s kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson\u27s correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). MEASUREMENTS AND MAIN RESULTS: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. CONCLUSION AND RELEVANCE: Our study confirms the feasibility and validity of an automated process to gather data from the EHR

Validation of automated data abstraction for SCCM discovery VIRUS COVID-19 registry: practical EHR export pathways (VIRUS-PEEP)

BackgroundThe gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities.ObjectiveThis study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients.Materials and methodsThis observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen’s kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson’s correlation coefficient and Bland–Altman plots. The strength of agreement was defined as almost perfect (0.81–1.00), substantial (0.61–0.80), and moderate (0.41–0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00–0.30), low (0.30–0.50), moderate (0.50–0.70), high (0.70–0.90), and extremely high (0.90–1.00).Measurements and main resultsThe cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%.Conclusion and relevanceOur study confirms the feasibility and validity of an automated process to gather data from the EHR

Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, setting, and participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main outcomes and measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P \u3c .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P \u3c .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P \u3c .001; 3 criteria: 817 patients with ARDS [19.3%]; P \u3c .001; 4 criteria: 203 patients with ARDS [24.3%]; P \u3c .001). Conclusions and relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Amit Jain’s surgical scoring system and its ability in predicting the major amputation in diabetic foot complications

There are numerous scoring system used in different parts of the world and most of them are for diabetic foot ulcers only with Amit Jain’s surgical scoring system being the first such scoring for diabetic foot complications. This study aims to validate the Amit Jain’s scoring system in predicting the risk of major amputation in diabetic foot complications. A retrospective analysis was done in Department of General Surgery of Raja Rajeswari medical college, Bengaluru, India. The study period was from January 2018 to December 2019. All the patients who underwent surgeries for diabetic foot complications in our department were included in the study. A total of 47 patients were included in this study. Majority of patients (76.6%) were males 61.7% of patients had diabetes mellitus of less than 10 years duration. Abscess was the most common pathological lesion seen in the foot affecting 36.17%. Most of the patients (59.6%) with diabetic foot complications had Amit Jain’s surgical score of 6-10 and were in low risk category.  12 patients (25.5%) underwent major amputation in this study and a significant association (P<0.001) was noted between Amit Jain’s surgical scoring and major amputation.&nbsp

In vivo intrinsic atomic interaction infer molecular eco-toxicity of industrial TiO(2 )nanoparticles via oxidative stress channelized steatosis and apoptosis in Paramecium caudatum

The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nano particles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 +/- 12 nm were synthesized with a zeta potential of 20.2 +/- 8.8 mV and bandgap of 4.6 +/- 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 mu g/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects

The paradigm of prophylactic viral outbreaks measures by microbial biosurfactants

The recent emergence and outbreak of the COVID-19 pandemic confirmed the incompetence of countries across the world to deal with a global public health emergency. Although the recent advent of vaccines is an important prophylactic measure, effective clinical therapy for SARS-Cov-2 is yet to be discovered. With the increasing mortality rate, research has been focused on understanding the pathogenic mechanism and clinical parameters to comprehend COVID-19 infection and propose new avenues for naturally occurring molecules with novel therapeutic properties to alleviate the current situation. In accordance with recent clinical studies and SARS-CoV-2 infection markers, cytokine storm and oxidative stress are entwined pathogenic processes in COVID-19 progression. Lately, Biosurfactants (BSs) have been studied as one of the most advanced biomolecules of microbial origin with anti-inflammatory, antioxidant, antiviral properties, antiadhesive, and antimicrobial properties. Therefore, this review inspects available literature and proposes biosurfactants with these properties to be encouraged for their extensive study in dealing with the current pandemic as new pharmaceutics in the prevention and control of viral spread, treating the symptoms developed after the incubation period through different therapeutic approaches and playing a potential drug delivery model