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International Journal of Molecular... Jun 2024Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced...
Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-β1, oxidative loads, Masson's trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis ( < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed ( < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity ( < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.
Topics: Animals; Bleomycin; Diaphragm; Mice; Fibrosis; Disease Models, Animal; Mice, Inbred C57BL; Acute Lung Injury; Male; Respiration, Artificial; Class Ib Phosphatidylinositol 3-Kinase; Transforming Growth Factor beta1; Apoptosis; Quinoxalines; Thiazolidinediones
PubMed: 38928077
DOI: 10.3390/ijms25126370 -
Bioengineering (Basel, Switzerland) Jun 2024The decision to extubate patients on invasive mechanical ventilation is critical; however, clinician performance in identifying patients to liberate from the ventilator...
The decision to extubate patients on invasive mechanical ventilation is critical; however, clinician performance in identifying patients to liberate from the ventilator is poor. Machine Learning-based predictors using tabular data have been developed; however, these fail to capture the wide spectrum of data available. Here, we develop and validate a deep learning-based model using routinely collected chest X-rays to predict the outcome of attempted extubation. We included 2288 serial patients admitted to the Medical ICU at an urban academic medical center, who underwent invasive mechanical ventilation, with at least one intubated CXR, and a documented extubation attempt. The last CXR before extubation for each patient was taken and split 79/21 for training/testing sets, then transfer learning with k-fold cross-validation was used on a pre-trained ResNet50 deep learning architecture. The top three models were ensembled to form a final classifier. The Grad-CAM technique was used to visualize image regions driving predictions. The model achieved an AUC of 0.66, AUPRC of 0.94, sensitivity of 0.62, and specificity of 0.60. The model performance was improved compared to the Rapid Shallow Breathing Index (AUC 0.61) and the only identified previous study in this domain (AUC 0.55), but significant room for improvement and experimentation remains.
PubMed: 38927862
DOI: 10.3390/bioengineering11060626 -
Antibiotics (Basel, Switzerland) May 2024Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed....
Accuracy of the Infectious Diseases Society of America and British Thoracic Society Criteria for Acute Pneumonia in Differentiating Chemical and Bacterial Complications of Aspiration in Comatose Ventilated Patients Following Drug Poisoning.
Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to overprescription of antibiotics and the emergence of multidrug-resistant bacteria. This study aims to assess the accuracy of the Infectious Diseases Society of America (IDSA) and British Thoracic Society (BTS) criteria in differentiating BAP from AP in comatose ventilated patients following drug poisoning. This cross-sectional study included 95 patients admitted for drug poisoning at the Lille University Hospital intensive care department, between 2013 and 2017, requiring mechanical ventilation and receiving antibiotics for aspiration. Patients were categorized as having bacterial complications if tracheal sampling yielded positive culture results, and if they were otherwise considered to have chemical complications. The sensitivity, specificity, positive predictive value, and negative predictive value of IDSA and BTS criteria in identifying patients with bacterial complications were evaluated. Among the patients, 34 (36%) experienced BAP. The IDSA criteria demonstrated a sensitivity of 62% and specificity of 33%, while the BTS criteria showed a sensitivity of 50% and specificity of 38%. Both the IDSA and BTS criteria exhibited poor sensitivity and specificity in identifying microbiologically confirmed pneumonia in comatose ventilated patients following drug poisoning.
PubMed: 38927162
DOI: 10.3390/antibiotics13060495 -
BMC Infectious Diseases Jun 2024There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels.
METHODS
The study analyzed data from the COMPILE study, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) assessing the efficacy of CCP vs. control, in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. SARS-CoV-2 IgG levels, referred to as 'dose' of CCP treatment, were retrospectively measured in donor sera or the administered CCP, semi-quantitatively using the VITROS Anti-SARS-CoV-2 IgG chemiluminescent immunoassay (Ortho-Clinical Diagnostics) with a signal-to-cutoff ratio (S/Co). The association between CCP dose and outcomes was investigated, treating dose as either continuous or categorized (higher vs. lower vs. control), stratified by recipient oxygen supplementation status at presentation.
RESULTS
A total of 1714 participants were included in the study, 1138 control- and 576 CCP-treated patients for whom donor CCP anti-SARS-CoV2 antibody levels were available from the COMPILE study. For participants not receiving oxygen supplementation at baseline, higher-dose CCP (/control) was associated with a reduced risk of ventilation or death at day 14 (OR = 0.19, 95% CrI: [0.02, 1.70], posterior probability Pr(OR < 1) = 0.93) and day 28 mortality (OR = 0.27 [0.02, 2.53], Pr(OR < 1) = 0.87), compared to lower-dose CCP (/control) (ventilation or death at day 14 OR = 0.79 [0.07, 6.87], Pr(OR < 1) = 0.58; and day 28 mortality OR = 1.11 [0.10, 10.49], Pr(OR < 1) = 0.46), exhibiting a consistently positive CCP dose effect on clinical outcomes. For participants receiving oxygen at baseline, the dose-outcome relationship was less clear, although a potential benefit for day 28 mortality was observed with higher-dose CCP (/control) (OR = 0.66 [0.36, 1.13], Pr(OR < 1) = 0.93) compared to lower-dose CCP (/control) (OR = 1.14 [0.73, 1.78], Pr(OR < 1) = 0.28).
CONCLUSION
Higher-dose CCP is associated with its effectiveness in patients not initially receiving oxygen supplementation, however, further research is needed to understand the interplay between CCP anti-SARS-CoV-2 IgG levels and clinical outcome in COVID-19 patients initially receiving oxygen supplementation.
Topics: Humans; COVID-19; Immunization, Passive; COVID-19 Serotherapy; Antibodies, Viral; SARS-CoV-2; Male; Middle Aged; Female; Immunoglobulin G; Aged; Treatment Outcome; Adult; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 38926676
DOI: 10.1186/s12879-024-09529-0 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support.
METHODS
A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital, involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS. The infants were randomly divided into a supine group (37 infants) and a prone group (40 infants). Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position, continuing in this cycle until weaning from the ventilator. The effectiveness and safety of the two approaches were compared.
RESULTS
At 6 hours after enrollment, the prone group showed lower arterial blood carbon dioxide levels, inspired oxygen concentration, oxygenation index, rates of tracheal intubation bacterial colonization, and Neonatal Pain, Agitation and Sedation Scale scores compared to the supine group (<0.05). There were no significant differences between the groups in terms of pH, arterial oxygen pressure, positive end-expiratory pressure, duration of mechanical ventilation, accidental extubation, ventilator-associated pneumonia, air leak syndrome, skin pressure sores, feeding intolerance, and grades II-IV intraventricular hemorrhage (>0.05).
CONCLUSIONS
Compared to supine positioning, prone ventilation effectively improves oxygenation, increases comfort, and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS, without significantly increasing adverse reactions.
Topics: Humans; Prone Position; Infant, Newborn; Respiratory Distress Syndrome, Newborn; Male; Female; Prospective Studies; Respiration, Artificial
PubMed: 38926379
DOI: 10.7499/j.issn.1008-8830.2312126 -
CNS Neuroscience & Therapeutics Jun 2024To evaluate the association between frailty and postoperative delirium (POD) in elderly cardiac surgery patients.
AIM
To evaluate the association between frailty and postoperative delirium (POD) in elderly cardiac surgery patients.
METHODS
A retrospective study was conducted of older patients admitted to the intensive care unit after cardiac surgery at a tertiary academic medical center in Boston from 2008 to 2019. Frailty was measured using the Modified Frailty Index (MFI), which categorized patients into frail (MFI ≥3) and non-frail (MFI = 0-2) groups. Delirium was identified using the confusion assessment method for the intensive care unit and nursing notes. Logistic regression models were used to examine the association between frailty and POD, and odds ratios (OR) with 95% confidence intervals (CI) were calculated.
RESULTS
Of the 2080 patients included (median age approximately 74 years, 30.9% female), 614 were frail and 1466 were non-frail. The incidence of delirium was significantly higher in the frail group (29.2% vs. 16.4%, p < 0.05). After adjustment for age, sex, race, marital status, Acute Physiology Score III (APSIII), sequential organ failure assessment (SOFA), albumin, creatinine, hemoglobin, white blood cell count, type of surgery, alcohol use, smoking, cerebrovascular disease, use of benzodiazepines, and mechanical ventilation, multivariate logistic regression indicated a significantly increased risk of delirium in frail patients (adjusted OR: 1.61, 95% CI: 1.23-2.10, p < 0.001, E-value: 1.85).
CONCLUSIONS
Frailty is an independent risk factor for POD in older patients after cardiac surgery. Further research should focus on frailty assessment and tailored interventions to improve outcomes.
Topics: Humans; Female; Male; Aged; Cardiac Surgical Procedures; Delirium; Frailty; Aged, 80 and over; Postoperative Complications; Retrospective Studies; Cohort Studies; Risk Factors
PubMed: 38924691
DOI: 10.1111/cns.14762 -
PloS One 2024Acute kidney injury is a prevalent complication in the Intensive Care Unit (ICU) and a significant global public health concern. It affects approximately 13 million...
BACKGROUND
Acute kidney injury is a prevalent complication in the Intensive Care Unit (ICU) and a significant global public health concern. It affects approximately 13 million individuals and contributes to nearly two million deaths worldwide. Acute kidney injury among Intensive Care Unit patients is closely associated with higher rates of morbidity and mortality. This study aims to assess the incidence of acute kidney injury and identify predictors among adult patients admitted to the medical Intensive Care Unit.
METHOD
A retrospective follow-up study was conducted by reviewing charts of 317 systematically selected patients admitted to the Intensive Care Unit from September 1, 2018, to August 30, 2022, in Wachemo University Nigist Ellen Mohammed Memorial Comprehensive Specialized Hospital. The extraction tool was used for the data collection, Epi-data version 4.6.0 for data entry, and STATA version 14 for data cleaning and analysis. The Kaplan-Meier, log-rank test, and life table were used to describe the data. The Cox proportional hazard regression model was used for analysis.
RESULTS
Among the total study participants, 128 (40.4%) developed Acute Kidney Injury (AKI). The incidence rate of Acute Kidney Injury was 30.1 (95% CI: 25.33, 35.8) per 1000 person-days of observation, with a median survival time of 23 days. It was found that patients with invasive mechanical ventilation (AHR = 2.64; 95% CI: 1.46-4.78), negative fluid balance (AHR = 2.00; 95% CI: 1.30-3.03), hypertension (AHR = 1.6; 95% CI: 1.05-2.38), and a vasopressor (AHR = 1.72; 95% CI: 1.10-2.63) were independent predictors of acute kidney injury.
CONCLUSION
The incidence of Acute Kidney Injury was a major concern in the ICU of the study area. In the intensive care unit (ICU), it was found that patients with vasopressors, invasive mechanical ventilation, negative fluid balance, and chronic hypertension were independent predictors of developing AKI. It would be better if clinicians in the ICU provided targeted interventions through close monitoring and evaluation of those patients with invasive ventilation, chronic hypertension, negative fluid balance, and vasopressors.
Topics: Humans; Acute Kidney Injury; Ethiopia; Intensive Care Units; Male; Female; Adult; Incidence; Middle Aged; Retrospective Studies; Risk Factors; Follow-Up Studies; Hospitals, Special; Aged; Young Adult
PubMed: 38924008
DOI: 10.1371/journal.pone.0304006 -
Critical Care Explorations Jul 2024COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked...
IMPORTANCE
COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point.
OBJECTIVES
To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.
DESIGN, SETTING, AND PARTICIPANTS
The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival.
MAIN OUTCOMES AND MEASURES
We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.
RESULTS
At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05-2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69-32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.
CONCLUSIONS
Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.
Topics: Humans; COVID-19; Middle Aged; Critical Illness; Male; Acute Kidney Injury; Female; Prospective Studies; Aged; Hepatitis A Virus Cellular Receptor 1; SARS-CoV-2; Adult; Biomarkers; Kidney Tubules; Creatinine; Intensive Care Units; Washington; Epidermal Growth Factor; Renal Replacement Therapy
PubMed: 38922318
DOI: 10.1097/CCE.0000000000001109 -
Toxins May 2024This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in...
Retrospective Evaluation of Clinical and Clinicopathologic Findings, Case Management, and Outcome for Dogs and Cats Exposed to (Eastern Coral Snake): 92 Cases (2021-2022).
This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in a university teaching hospital setting. The medical records of dogs and cats that received antivenom following coral snake exposure were reviewed. Data collected included signalment, time to antivenom administration, physical and laboratory characteristics at presentation, clinical course during hospitalization, length of hospitalization, and survival to discharge. The mean time from presentation to coral snake antivenom administration was 2.26 ± 1.46 h. Excluding cases where the owner declined in-hospital care, the mean hospitalization time for dogs and cats was 50.8 h and 34 h, respectively. The mean number of antivenom vials was 1.29 (1-4). Gastrointestinal signs (vomiting and ptyalism) occurred in 42.2% (35/83) of dogs and 33.3% (3/9) of cats. Peripheral neurologic system deficits (ataxia, paresis to plegia, absent reflexes, and hypoventilation) were noted in 19.6% (18/92) of dogs and cats. Hemolysis was also common in 37.9% (25/66) of dogs but was not observed in cats. Mechanical ventilation (MV) was indicated in 12% (10/83) of dogs but no cats. Acute kidney injury (AKI), while rare, was a common cause of euthanasia at 20% (2/5) and was the most common complication during MV at 44.4% (4/9). Pigmenturia/hemolysis occurred in 88.9% (8/9) of MV cases and in all cases with AKI. Despite delays in antivenom administration by several hours, dogs and cats with coral snake exposure have low mortality rates (6% of dogs (5/83) and 0% of cats). Gastrointestinal signs were common but were not predictive of progression to neurological signs. Thus, differentiating between coral snake exposure and envenomation before the onset of neurological signs remains challenging.
Topics: Animals; Dogs; Antivenins; Retrospective Studies; Cats; Coral Snakes; Snake Bites; Cat Diseases; Elapid Venoms; Male; Female; Dog Diseases; Treatment Outcome; Venomous Snakes
PubMed: 38922141
DOI: 10.3390/toxins16060246 -
Pathogens (Basel, Switzerland) Jun 2024Nosocomial pneumonia (NP) represents a leading nosocomial infection and results in substantial morbidity and cost. Over the last several years, the evidence has evolved... (Review)
Review
Nosocomial pneumonia (NP) represents a leading nosocomial infection and results in substantial morbidity and cost. Over the last several years, the evidence has evolved which directs our approach to NP. Specifically, the definition of NP and classification of its various subtypes has expanded to capture nuances among various phenotypes of this syndrome. For example, segregating those with hospital-acquired pneumonia (HAP) based on whether they subsequently require mechanical ventilation has been shown to be important. Likewise, newer data indicate the true economic cost of NP and underscore the diverse range of pathogens that can cause NP. Moreover, multidrug-resistant (MDR) bacteria have become a major threat in NP. Fortunately, newer simple preventive strategies have been tested and found to be effective at reducing the incidence of NP. Should prevention fail, a range of new antibiotics have been formally studied in NP and found to be effective. Some of these novel agents have relatively broad ranges of activity and are in vitro active against select MDR organisms. Others, however, are narrower in spectrum and directed against specific problem bacteria. In short, the literature in the field of NP has progressed rapidly, and clinicians require a clear appreciation of these changes so as to improve patient outcomes.
PubMed: 38921793
DOI: 10.3390/pathogens13060495