Need For Ventilatory Support Research Articles

Effects of Buprenorphine, Methadone, and Substance-Use on COVID-19 Morbidity and Mortality.

Substance use disorder has been associated with increased morbidity in COVID-19 infection. However, less is known about the impact of active substance use and medications for opioid use disorder (MOUD) on COVID-19 outcomes. We conducted a retrospective cohort study to evaluate the impact of substance use, namely, cannabis, cocaine, alcohol, sedative and opioid use; and buprenorphine or methadone on COVID-19 morbidity and mortality. Using electronic health record data at a large urban hospital system, patients who tested positive for COVID-19 between January 1, 2020, and December 31, 2021, were included. Substance use was identified from urine toxicology and MOUD prescriptions within 90 days prior to admission. COVID-19 outcomes included mortality, ICU admission, need for intubation, and number and duration of hospitalizations. Multivariable logistic regression was performed controlling for variables such as age, sex, medical comorbidity, tobacco use, and social disadvantage. Among COVID-19-positive patients (n = 17,423), sedative, cannabis, cocaine, and opioid use was associated with statistically significant increases in need for ICU care, need for ventilatory support, number of hospitalizations, and duration of hospitalization. Substance use was not associated with an increase in all-cause mortality. There were no statistically significant differences between methadone, buprenorphine, and other opioids on COVID-19 outcomes. Active substance use was associated with increased morbidity in COVID-19 infection. MOUD was not associated with worse COVID-19 outcomes compared to other opioids. Future studies focused on MOUD treatments that reduce morbidity may help improve clinical outcomes in COVID-19.

The need for assisted ventilation corroborates the effectiveness of antenatal corticosteroid therapy in preventing premature lamb mortality

In premature births, deficiency and/or inactivation of surfactant and incomplete development of lung occur, leading to pulmonary complications and greater need for ventilatory interventions. Prenatal corticosteroid therapy is used to improve neonatal lung function and, thus, may reduce mortality and lower incidence and severity of lung injury. Therefore, this study aimed to assess the need for ventilatory support in preterm lambs subjected or not to prenatal betamethasone treatment, and to evaluate the effectiveness on neonatal survival. Lambing was induced and 13 premature lambs were assigned to Corticosteroid Group (n = 8; lambs from ewes subjected previously to 0.5 mg/kg betamethasone, IM, at 133 days of pregnancy) and Control Group (n = 5; non-treated lambs). Lambs were evaluated for vitality, neurologic reflexes, vital functions and birth weight. Three ventilatory modalities were preconized for critical lambs, according to specific criteria: mask oxygen therapy, self-inflating bag with tracheal tube and mechanical ventilation. Non-treated lambs had lower vitality score, muscle tonus and respiratory rate compared to Corticosteroid Group. Ventilatory support was needed for 3 Control lambs and only 1 Corticosteroid neonate. Corticosteroid lamb required significant less time-frame between birth and onset of ventilatory assistance and remained under ventilation for a shorter time. Percentage of ventilated non-treated lambs correlated negatively with birth weight, muscle tone, heart and respiratory rate. In conclusion, antenatal betamethasone treatment reduces the need for ventilatory assistance in premature lambs. Additionally, mortality is low when a protocol for inducing pulmonary maturity (maternal corticosteroid therapy) and/or ventilatory interventions are employed, ensuring the survival of premature lambs.

Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study

Remdesivir (Veklury, Gilead Sciences, Foster City, CA, USA) and nirmatrelvir-ritonavir (Paxlovid, Pfizer, New York, NY, USA) were reported to improve the outcome of patients with mild-to-moderate COVID-19 symptoms. Preclinical data suggest that nirmatrelvir-ritonavir might be more effective than remdesivir alone or in combination with nirmatrelvir-ritonavir for people at high risk of severe COVID-19. We aimed to assess the safety and effectiveness of combining remdesivir and nirmatrelvir-ritonavir compared with using each drug alone for adults hospitalised with COVID-19. In this target trial emulation study, we used electronic health records of patients aged 18 years or older who received either combination treatment of nirmatrelvir-ritonavir and remdesivir or monotherapy of either drug between March 16 and Dec 31, 2022, within 5 days of hospitalisation for COVID-19 in Hong Kong. Inverse probability of treatment weighting was applied to balance baseline patient characteristics across the treatment groups. The primary outcome was all-cause mortality. Cox proportional hazards regression adjusting weighting was used to compare the risk of all-cause mortality, intensive care unit (ICU) admission, or ventilatory support for 90 days of follow-up between groups. Between March 16 and Dec 31, 2022, 18 196 participants were identified from electronic health records and assigned to receive remdesivir (n=4232), nirmatrelvir-ritonavir (n=13 656), or nirmatrelvir-ritonavir and remdesivir (n=308). By applying an inverse probability of treatment weighting, a weighted sample composed of 18 410 recipients of nirmatrelvir-ritonavir and remdesivir combination treatment, 18 178 recipients of remdesivir monotherapy, and 18 287 recipients of nirmatrelvir-ritonavir monotherapy was obtained. After a median follow-up of 84 days (IQR 45-90), risk of mortality was lower in patients who received nirmatrelvir-ritonavir monotherapy (hazard ratio [HR] 0·18 [95% CI 0·15 to 0·20]; absolute risk reduction [ARR] -16·33% [95% CI -16·98 to -15·68]) or remdesivir and nirmatrelvir-ritonavir combination therapy (HR 0·66 [95% CI 0·49 to 0·89]; ARR -6·52% [95% CI -7·29 to -5·74]) than in patients who received remdesivir monotherapy. Similar results were observed for ICU admission or ventilatory support (nirmatrelvir-ritonavir monotherapy: HR 0·09 [95% CI 0·07 to 0·11]; ARR -10·04% [95% CI -10·53 to -9·56]; combination therapy: HR 0·68 [95% CI 0·42 to 1·12]; ARR -3·24% [95% CI -3·84 to -2·64]). Compared with combination therapy, nirmatrelvir-ritonavir monotherapy was associated with lower risk of mortality (HR 0·27 [95% CI 0·20 to 0·37]; ARR -9·81% [95% CI -10·39 to -9·24]) and ICU admission or ventilatory support (HR 0·13 [95% CI 0·08 to 0·22]; ARR -6·80% [95% CI -7·22 to -6·39]). Our study highlighted the potential for reduced risk of mortality, ICU admission, or the need for ventilatory support in patients hospitalised with COVID-19 treated with nirmatrelvir-ritonavir as a monotherapy compared with treatment regimens based on nirmatrelvir-ritonavir and remdesivir combination therapy or remdesivir monotherapy. Further randomised controlled trials are needed to support the validity of the current results. The Health and Medical Research Fund Commissioned Research on COVID-19. For the Chinese translation of the abstract see Supplementary Materials section.

A cross-sectional study of neutrophil to lymphocyte ratio as a prognostic marker in acute organophosphorus poisoning in a tertiary care hospital in Central India

Background Acute organophosphorus poisoning remains a significant public health concern, with variable clinical outcomes. Prognostic markers are crucial for patient management and risk stratification. This study aims to investigate the Neutrophil Lymphocyte Ratio (NLR) as a potential prognostic marker and its associations with severity and clinical outcomes in acute organophosphorus poisoning. Methods This cross-sectional observational study will be conducted over two years, involving patients presenting with acute organophosphorus poisoning in the Medicine Ward and Intensive Care Unit of DMIHER Wardha. Informed consent will be obtained, and detailed clinical assessments, laboratory investigations, and NLR calculations will be performed. The Nambaet, Peradeniya, and Bardin classification scales will be used to measure severity. Statistical methods will be applied to explore the relationships between NLR, clinical parameters, and clinical outcomes, including descriptive statistics, bivariate analysis, correlation analysis, multivariate regression, and ROC analysis. Expected Results The study is anticipated to elucidate the role of NLR as a prognostic marker in acute organophosphorus poisoning. Initial assessments and correlations between NLR and clinical parameters will be presented. The predictive capability of NLR for clinical outcomes, including the need for ventilatory support and length of hospital stay, will be explored. Agreement and discrepancies between the classification scales will be evaluated.

Fetal Dilated Myocardiopathy – Case Report: Association with a heterozygous mutation in MYH7 gene

We report a case of dilated myocardiopathy with ascites and cardiac dysfunction detected at 20 weeks’ gestation. Baby was born at 33 weeks and 6 days, weighing 2530g, delivered by cesarean section and admitted to NICU. Postnatal echocardiography confirmed biventricular severe dysfunction, need of ventilatory support, vasoactive drugs, and prostaglandins. He was investigated for metabolic, infectious, and viral diseases with no positive results. After 6 weeks, he was transferred to a transplant center. Exome sequence showed a heterozygous mutation in the MYH7 gene (OMIN-160760.0028).

High-sensitive troponinT, interleukin-8, and interleukin-6 link with post-surgery risk in infant heart surgery.

This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.

Neurological manifestations and complications of COVID-19 in patients admitted to a tertiary care center in Nepal during the second wave.

Neurological symptoms and signs of Coronavirus disease-19 (COVID-19) can accompany, follow, or precede respiratory symptoms and signs; hence, they are important in the diagnosis and management of COVID-19 patients. In this retrospective study conducted during the second wave of COVID-19, we included all patients diagnosed with COVID-19 using real-time polymerase chain reaction and admitted to the Tribhuvan University Teaching Hospital between June 2021 and October 2021. The patients were categorized into 2 groups: group A (with neurological manifestations or complications) and Group-B (without neurological manifestations or complications). The 2 groups were compared in terms of intensive care unit (ICU) admission, need for ventilatory support, length of hospital stay, and various outcomes. The study included 235 participants ranging in age from 13 to 102 years (mean age = 54 years, standard deviation = 18). Among the participants, 54.50% were male. The proportion of individuals in group A was higher (59.15%, N = 139) than that in Group-B (40.85%, N = 96). Notably, a significantly greater number of patients were admitted to the ICU in Group B than in Group A. However, there were no statistically significant differences in the need for ventilatory support or hospital stay between the 2 groups. Interestingly, group A showed a higher rate of improvement (Z = -3.1145, P = .00188, 95% CI), while Group-B had a higher rate of mortality (Z = 4.5562, P < .00001, 95% CI). Altered mental status and stroke have been specifically linked to poorer outcomes, whereas typical neurological manifestations, such as hyposmia, hypogeusia, dizziness, headache, and myalgia, are associated with better outcomes.

Type 2 Diabetes Status, Diabetes Complication Severity Index Scores, and Their Relationship With COVID-19 Severity: A Retrospective Cohort Study of Hospitalized Patients in a Southwest Virginia Health System.

Background Studies have shown that patients with type 2 diabetes mellitus (T2DM) tend to have poorer outcomes associated with COVID-19, including increased rates of hospitalization, ICU admission, need for ventilatory support, and mortality. Methods We performed a retrospective cohort study that included all non-pregnant adult patients who were hospitalized as a result of COVID-19 in a Southwest Virginia health system between March 18, 2020, and August 31, 2022. T2DM status was treated as a binary variable. T2DM severity was assessed using the Diabetes Complications Severity Index (DCSI). Multivariate logistic regression was used to assess the relationship between T2DM status and COVID-19 severity outcomes. Multivariate logistic regression was also used to assess the relationship between DCSI score and COVID-19 severity outcomes among patients with an established diagnosis of T2DM at the time of COVID-19 hospital admission. Results Patients with T2DM had 1.27 times the odds of experiencing a poor COVID-19 clinical outcome (95% CI: 1.13, 1.43) and 1.35 times the odds of in-hospital mortality (95% CI: 1.14, 1.59) compared to patients without diabetes. Among patients with T2DM, increasing DCSI score was significantly associated with increased odds of experiencing a poor COVID-19 clinical outcome and in-hospital mortality. Conclusions Diabetic patients in our sample were at increased odds of experiencing poor COVID-19 clinical outcomes and in-hospital mortality compared to individuals without diabetes. Amongst patients with T2DM, increasing DCSI score was associated with worse COVID-19 outcomes. Clinical decision support tools may be able to utilize DCSI scores as an indicator of COVID-19 severity risk to facilitate decisions regarding treatment aggressiveness and resource allocation.

The influence of prenatal dexamethasone administration before scheduled full-term cesarean delivery on short-term adverse neonatal outcomes: a retrospective single-center cohort study.

There has been a gradual increase in the prevalence of cesarean section deliveries and more healthcare professionals are considering the prophylactic use of corticosteroids before planned full-term cesarean sections. However, the association between dexamethasone administration before full-term cesarean delivery and short-term adverse neonatal outcomes is unclear. This study analyzed the disparities in short-term adverse neonatal effects in neonates born via full-term elective cesarean delivery with or without antenatal dexamethasone treatment. This single-center retrospective cohort study involved neonates aged 37-39 weeks. The primary neonatal outcomes included various short-term adverse events, including neonatal admission to the neonatal intensive care unit, neonatal access to the special care baby unit, transient neonatal respiratory distress, respiratory distress syndrome, and the requirement of intravenous antibiotics or ventilatory support. Multiple logistic regression analysis was used to assess the association between these outcomes and dexamethasone exposure while adjusting for covariates. Of the 543 neonates included in the study, 121 (22.2%) had been exposed to prenatal dexamethasone. When compared with the control group, the dexamethasone-exposed group exhibited significantly higher rates of transient neonatal respiratory distress, respiratory distress syndrome, administration of intravenous antibiotics, the need for ventilatory support, and longer duration of neonatal hospitalization (P < 0.05). The association between dexamethasone exposure and short-term adverse neonatal outcomes remained significant after adjusting for potential confounders (odds ratio: 12.76, 95% confidence interval: 6.9-23.62, P < 0.001). The dexamethasone-exposed group had a higher likelihood of experiencing short-term adverse outcomes when compared with non-exposed neonates, suggesting that dexamethasone may have detrimental effects on infants delivered at full term. This implies the importance of exercising caution when contemplating the use of antenatal corticosteroids.

A Comparative Study on the General and Otolaryngological Manifestations of COVID-19 in the Hospitalized Population of the Telangana Region During the First and Second Waves.

Introduction Some common symptoms of coronavirus disease 2019 (COVID-19) are fever, cough, and shortness of breath. But ear, nose, and throat (ENT) manifestations such as loss of smell and taste are also very common. Objectives To compare the general and otorhinolaryngological manifestations of COVID-19 and to compare the treatments given and mortality rate during its two waves. Methods This retrospective study was conducted on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases in a tertiary care teaching hospital. Six hundred patients were included in the 1st wave sample and 516 were in the 2nd wave sample. The data collected included demographics, comorbidities, general, and ENT symptoms, need for ventilatory support, oxygen therapy, and mortality for both the waves. Results Fever, malaise, and myalgia were more frequently presented in the first wave than in the second, whereas shortness of breath was more common in the second wave. In the second wave, a significant increase in anosmia cases was reported, whereas sore throat, nasal obstruction, dysphagia, nasal discharge, and sneezing were significantly reduced compared with the first wave ( p < 0.001). The case fatality rate increased from 11.33 to 21.55% ( p < 0.001) from the 1 st to the 2 nd wave. The patients who died in the second wave were younger than those in the first wave. Two doses of vaccination showed protection from the death over those not vaccinated and those who only received one dose ( p < 0.05). Conclusion Ear, nose, and throat (ENT) manifestations are very common along with the general symptoms. As anosmia and dysgeusia are early presenting symptoms in COVID-19 patients, all physicians should screen patients for ENT symptoms.

A Study to Evaluate the Complications of Laparoscopic Renal and Adrenal Surgeries Using Modified Clavien-Dindo Classification

Background: Laparoscopic surgery has become a widely accepted approach for the treatment of renal and adrenal diseases. However, there is a need to assess the post-operative complications associated with these procedures using standardized classification systems. The modified Clavien-Dindo classification system offers a comprehensive framework for evaluating surgical outcomes and determining the severity of complications. Methods: This prospective study involved 106 patients who underwent laparoscopic renal and adrenal resective surgeries. Post-operative complications were recorded and graded according to the modified Clavien-Dindo classification system. The data collected were analysed to assess the incidence and severity of complications in relation to patient demographics, comorbidities, and surgical procedures. Results: Among the 106 patients, 16.03% experienced post-operative complications, with 13.20% classified as minor complications and 2.83% as major complications. The most common minor complications included delayed bowel movements and wound infection, while major complications included conversion to open surgery and the need for ventilator support or haemodialysis. No deaths were reported in the study. The association between complication rates and age, gender, ASA grade, side of pathology, comorbidities, and pathology/diagnosis was not statistically significant. However, higher grade complications tended to occur more frequently in elderly patients, males, and those with comorbidities. Conclusions: This study supports the effectiveness of laparoscopic surgery for renal and adrenal diseases, as evidenced by low complication rates. The modified Clavien-Dindo classification system proved valuable in assessing and categorizing post-operative complications, enabling a comprehensive evaluation of surgical outcomes. Implementation of this standardized classification system can contribute to improving patient safety and the overall quality of surgical care. Further research with larger sample sizes and longer follow-up periods is recommended to obtain more precise and comprehensive data on long-term morbidity and mortality associated with laparoscopic renal and adrenal resective surgeries.

Cytomegalovirus Reactivation in Severe Coronavirus Disease 2019: Case Series from a Tertiary Care Center in the Western State of India

Abstract Introduction: Cytomegalovirus (CMV) reactivation in patients who have been admitted to the intensive care unit (ICU) is linked to higher mortality and health-care costs. There is a dearth of published research on CMV reactivation in patients with severe SARS-CoV-2. Materials and Methods: Objectives: The objective of this study was to describe clinical and laboratory profiles and outcomes of CMV reactivation in patients with severe SARS-CoV-2 illness. In this retrospective study carried out at a tertiary care hospital ICU in the Western state of India, patients with severe SARS-CoV-2 who were admitted from January 1, 2021, to May 31, 2021, and who got CMV viral load testing by reverse transcriptase polymerase chain reaction were analyzed. Results: During the study period, 27 out of 277 admitted patients were subjected to plasma CMV viral load testing, of which 13 patients had detectable viral load giving a prevalence of 4.7%. Patients who tested positive for CMV had significantly higher mortality (P = 0.020) and ventilator support needs (P = 0.004). Both fungal and bacterial bloodstream infections were frequent in CMV-positive patients, but neither was statistically significant (P = 0.065 and P = 0.571, respectively). In this case series, there was no difference in CMV reactivations according to the degree of lymphopenia (P = 0.149), usage of steroids (P = 0.766), or immunomodulatory medications (tocilizumab/bevacizumab, P = 0.926). Conclusions: In SARS-CoV-2 patients with severe illness, CMV reactivation was associated with an increased need for ventilator support, a higher incidence of nosocomial infection (bacterial and fungal), and overall mortality.

Assessment of Skin Maturity by LED Light at Birth and Its Association With Lung Maturity: Clinical Trial Secondary Outcomes

Background Clinicians face barriers when assessing lung maturity at birth due to global inequalities. Still, strategies for testing based solely on gestational age to predict the likelihood of respiratory distress syndrome (RDS) do not offer a comprehensive approach to addressing the challenge of uncertain outcomes. We hypothesize that a noninvasive assessment of skin maturity may indicate lung maturity. Objective This study aimed to assess the association between a newborn’s skin maturity and RDS occurrence. Methods We conducted a case-control nested in a prospective cohort study, a secondary endpoint of a multicenter clinical trial. The study was carried out in 5 Brazilian urban reference centers for highly complex perinatal care. Of 781 newborns from the cohort study, 640 were selected for the case-control analysis. Newborns with RDS formed the case group and newborns without RDS were the controls. All newborns with other diseases exhibiting respiratory manifestations were excluded. Skin maturity was assessed from the newborn's skin over the sole by an optical device that acquired a reflection signal through an LED sensor. The device, previously validated, measured and recorded skin reflectance. Clinical data related to respiratory outcomes were gathered from medical records during the 72-hour follow-up of the newborn, or until discharge or death, whichever occurred first. The main outcome measure was the association between skin reflectance and RDS using univariate and multivariate binary logistic regression. Additionally, we assessed the connection between skin reflectance and factors such as neonatal intensive care unit (NICU) admission and the need for ventilatory support. Results Out of 604 newborns, 470 (73.4%) were from the RDS group and 170 (26.6%) were from the control group. According to comparisons between the groups, newborns with RDS had a younger gestational age (31.6 vs 39.1 weeks, P&lt;.001) and birth weight (1491 vs 3121 grams, P&lt;.001) than controls. Skin reflectance was associated with RDS (odds ratio [OR] 0.982, 95% CI 0.979-0.985, R2=0.632, P&lt;.001). This relationship remained significant when adjusted by the cofactors antenatal corticosteroid and birth weight (OR 0.994, 95% CI 0.990-0.998, R2=0.843, P&lt;.001). Secondary outcomes also showed differences in skin reflectance. The mean difference was 0.219 (95% CI 0.200-0.238) between newborns that required ventilatory support versus those that did not and 0.223 (95% CI 0.205-0.241) between newborns that required NICU admission versus those that did not. Skin reflectance was associated with ventilatory support (OR 0.996, 95% CI 0.992-0.999, R2=0.814, P=.01) and with NICU admission (OR 0.994, 95% CI 0.990-0.998, R2=0.867, P=.004). Conclusions Our findings present a potential marker of lung immaturity at birth using the indirect method of skin assessment. Using the RDS clinical condition and a medical device, this study demonstrated the synchrony between lung and skin maturity. Trial Registration Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR-3f5bm5; https://tinyurl.com/9fb7zrdb International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2018-027442

Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection.

Among patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management. A multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014-2019 was performed. Groups were stratified by vHABP, nvHABP, and VABP and compared on demographics, clinical characteristics, treatment, and outcomes. Multivariable models were generated via machine learning to identify risk factors for progression to vHABP as well as pneumonia-associated mortality for each cohort. 457 patients (32% nvHABP, 37% vHABP, and 31% VABP) were evaluated. The vHABP and nvHABP groups were similar in age (median age 66.4 years) with 77% having multiple comorbidities but more vHABP patients had liver disease (18.2% vs. 7.7% p = 0.005), alcohol use disorder (27% vs. 7.1%, p < 0.0001), and were hospitalized within the past 30 days (30.4% vs. 19.5%, p = 0.02). An immediate need for ventilatory support occurred in 70% of vHABP patients on the day of diagnosis. Mortality was the highest in vHABP followed by VABP and nvHABP groups (44.6% vs. 36% vs. 14.3%, p < 0.0001). Nearly all (96%) vHABP patients had positive cultures, with Gram-negative pathogens accounting for 58.8% whereby 33.0% were resistant to extended-spectrum β-lactams (ESBLs), ceftriaxone (17.5%), fluoroquinolones (20.6%), and carbapenems (12.4%). Up to half of the vHABP patients with ESBL-Enterobacterales or P. aeruginosa did not receive an effective empiric regimen; over 50% increase in mortality rate was observed among patients whom effective therapy was initiated past the day of pneumonia diagnosis. Risk factors associated with vHABP development were alcohol use disorder, APACHE II score, vasopressor therapy prior to infection, and culture positive for ESBL-Enterobacterales whereas history of hospitalization in the past 30 days, active malignancy, isolation of ceftriaxone-resistant pathogens or Pseudomonas aeruginosa, and vasopressor therapy were risk factors for vHABP-associated mortality. Patients with vHABP experienced an acute and severe decompensation upon diagnosis. The risk factors identified in this study could provide actionable data for clinicians to identify those at risk for vHABP at the onset of pneumonia and to target antimicrobial stewardship efforts to improve treatment success.

Neutrophil Extracellular Traps Are Induced by Coronavirus 2019 Disease-Positive Patient Plasma and Persist Longitudinally: A Possible Link to Endothelial Dysfunction as Measured by Syndecan-1.

Background: Neutrophil extracellular trap (NET) formation is a mechanism that neutrophils possess to respond to host infection or inflammation. However, dysregulation of NETosis has been implicated in many disease processes. Although the exact mechanisms of their involvement remain largely unknown, this study aimed to elucidate NET formation over the time course of coronavirus disease 2019 (COVID-19) infection and their possible role in endothelial injury. Patients and Methods: Plasma samples from COVID-19-positive patients were obtained at six timepoints during hospitalization. Neutrophils were extracted from healthy donors and treated with COVID-19-positive patient plasma. Myeloperoxidase (MPO) assay was used to assess for NETosis. Syndecan-1 (SDC-1) enzyme-linked immunosorbent assay (ELISA) was run using the same samples. Immunocytochemistry allowed for further quantification of NETosis byproducts MPO and citrullinated histone 3 (CitH3). The receiver operating characteristic (ROC) curve discriminated between admission levels of SDC-1 and MPO in predicting 30-day mortality and need for ventilator support. Results: Sixty-three patients with COVID-19 were analyzed. Myeloperoxidase was upregulated at day 3, 7, and 14 (p = 0.0087, p = 0.0144, p = 0.0421). Syndecan-1 levels were elevated at day 7 and 14 (p = 0.0188, p = 0.0026). Neutrophils treated with day 3, 7, and 14 plasma expressed increased levels of MPO (p < 0.001). Immunocytochemistry showed neutrophils treated with day 3, 7, and 14 plasma expressed higher levels of MPO (p < 0.001) and higher levels of CitH3 when treated with day 7 and 14 plasma (p < 0.01 and p < 0.05). Admission SDC-1 and MPO levels were found to be independent predictors of 30-day mortality and need for ventilator support. Conclusions: Neutrophil dysregulation can be detrimental to the host. Our study shows that COVID-19 plasma induces substantial amounts of NET formation that persists over the course of the disease. Patients also exhibit increased SDC-1 levels that implicate endothelial injury in the pathogenesis of COVID-19 infection. Furthermore, MPO and SDC-1 plasma levels are predictive of poor outcomes.

Use of Remdesivir in Patients Hospitalized for COVID-19 Pneumonia: Effect on the Hypoxic and Inflammatory State.

Remdesivir is one of the most attractive options for patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). The aim of our study was to evaluate the effect of remdesivir on the hypoxic and inflammatory state in patients with moderate to severe COVID-19. We retrospectively enrolled 112 patients admitted for COVID-19 pneumonia, requiring low-flow oxygen, 57 treated with remdesivir plus standard of care (SoC) and 55 treated only with SoC that were similar for demographic and clinical data. We evaluated changes in hypoxemia and inflammatory markers at admission (Day 0) and after 5 days of treatment (Day 5) and the clinical course of the disease. From Day 0 to Day 5, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) increased from 222 ± 62 to 274 ± 97 (p < 0.0001) in the remdesivir group and decreased from 223 ± 62 to 183 ± 76 (p < 0.05) in the SoC group. Interleukine-6 levels decreased in the remdesivir (45.9 to 17.5 pg/mL, p < 0.05) but not in the SoC group. Remdesivir reduced the need for ventilatory support and the length of hospitalization. In conclusion, compared to standard care, remdesivir rapidly improves hypoxia and inflammation, causing a better course of the disease in moderate to severe COVID-19.

Severe Influenza Virus and Respiratory Syncytial Virus Infections in Intensive Care Over the Last 15 Years.

Influenza virus is a common agent of pediatric infections. Most cases are mild, but severe illness and death can occur. We aimed to analyze severe cases associated the influenza virus and compare it with respiratory syncytial virus(RSV). This is a retrospective study of 0-17-year-old patients admitted to the intensive care unit (ICU) of Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra (Pediatric Hospital, Coimbra Hospital and University Center), a tertiary pediatric hospital in Coimbra, Portugal, over the last 15 years (2008-2022) due to influenza virus infection. Clinical presentation, severity, and evolution were analyzed. A comparison of children with RSV infection admitted in the same period was performed. We identified 47 cases of influenza virus infection (34% coinfection with other viruses), median age of 2.3 years (interquartile range (IQR) 6.1), and 38% had comorbidities. The median admissions were three/year (maximum 11 in 2019). Influenza A was identified in 96%. Ninety-six percent had respiratory symptoms, 38% had neurologic symptoms, and 28% had sepsis. The main reason for admission was respiratory failure (68%). The mean pediatric index of mortality 2 (PIM2) at admission was 9±15.9%. Ventilatory support was necessary in 66%, vasoactive support in 19%, and blood products in 17%. The median length of stay was four days (IQR 5). There were four (8.5%) deaths. During the same study period, there were 171 RSV-related admissions. When comparing influenza (group A, without RSV coinfection) and RSV (group B), the first had a higher PIM2 on admission, greater need of ventilatory support, more complications, and higher mortality (p=0.001). The number of influenza virus infections admitted to ICU was much lower than RSV. However, influenza was more severe and associated with all deaths registered.

The utility of diaphragm ultrasound thickening indices for assessing respiratory decompensation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) leads to diaphragmatic weakness at some point during its course, which is a major cause of respiratory insufficiency. The aim of this study was to evaluate ultrasound-based measures for assessing the diaphragmatic competency and the need for ventilatory support. Twenty-six subjects with ALS and 12 healthy controls were enrolled. All participants underwent B-mode diaphragm ultrasound (DUS). Diaphragm thickness and thickening indices were recorded. In the subjects with ALS, further assessments included functional scales and spirometry. We investigated the diagnostic accuracy of DUS thickening indices in predicting diaphragmatic dysfunction and the correlation between clinical, spirometric, and DUS data. Significant relationships were found between forced vital capacity and all diaphragmatic thickening indices. Similarly, all diaphragmatic thickening indices correlated with both Milano Torino staging and disease progression rate. Only thickening fraction (TFdi) correlated with score on the revised ALS Functional Rating Scale (r = 0.459, P = .024). TFdi had better accuracy in predicting diaphragmatic dysfunction (area under the curve [AUC] = 0.839, 95% confidence interval [CI] 0.643 to 0.953) and the need for initiation of noninvasive ventilation (NIV) (AUC = 0.989, 95% CI 0.847 to 1.000) compared with the other indices. A TFdi cut-off point of 0.50 was a sensitive threshold to consider NIV. DUS successfully identifies diaphragmatic dysfunction in ALS, being a valuable accessory modality for investigating respiratory symptoms. TFdi was found to be the most useful DUS index, which encourages further investigation.

Pulmonary Function Assessment in Myasthenia Gravis Patients in a National Referral Hospital in Indonesia.

Myasthenia gravis (MG) can cause respiratory muscle weakness and the need of ventilator support. Spirometry as the gold standard for pulmonary function examination has limited availability, especially in our hospital which is only available in outpatient clinic during work hours (not in emergency room or patient room). Furthermore, all primary healthcare in Indonesia do not have spirometry equipment, thus other alternatives are required. This study aimed to analyze the relationship between a single breath counting test (SBCT), peak flow meter (PFM), and spirometry to assess pulmonary function in MG patients in a national referral hospital in Indonesia. A single-center, cross-sectional study was conducted and SBCT, PFM, and spirometry examination were performed in MG patients and healthy controls. Seventy patients, aged 47.7 ± 13.4 years old, participated in this study. SBCT, forced vital capacity first second (FVC1), and forced expiratory volume first second (FEV1) value between MG patients and healthy controls showed a significant difference, in which healthy controls have higher SBCT, FVC1, and FEV1 values (p = 0.000, p = 0.000 and p = 0.001 respectively). There was a significant difference between PFM with SBCT and FVC1 value in MG patients. Strong correlation was found between SBCT and FVC1 in MG patients. MG patients had worse pulmonary function compared to healthy controls. SBCT and PFM examination have a significant correlation with FVC1 in MG patients. Therefore, SBCT and PFM can be used as a bedside tool to detect respiratory impairment in MG patients.

International Pediatric COVID-19 Severity Over the Course of the Pandemic

Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. SARS-CoV-2 hospitalization during the stipulated time frame. The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.