The advanced learning paradigm, learning using privileged information (LUPI), leverages information in training that is not present at the time of prediction. In this study, we developed privileged logistic regression (PLR) models under the LUPI paradigm to detect acute respiratory distress syndrome (ARDS), with mechanical ventilation variables or chest x-ray image features employed in the privileged domain and electronic health records in the base domain. In model training, the objective of privileged logistic regression was designed to incorporate data from the privileged domain and encourage knowledge transfer across the privileged and base domains. An asymptotic analysis was also performed, yielding sufficient conditions under which the addition of privileged information increases the rate of convergence in the proposed model. Results for ARDS detection show that PLR models achieve better classification performances than logistic regression models trained solely on the base domain, even when privileged information is partially available. Furthermore, PLR models demonstrate performance on par with or superior to state-of-the-art models under the LUPI paradigm. As the proposed models are effective, easy to interpret, and highly explainable, they are ideal for other clinical applications where privileged information is at least partially available.

BACKGROUND: COVID-19 is a viral infection affecting the respiratory system, primarily. It has spread globally ever since it first appeared in China in 2019. The use of high-flow nasal oxygen (HFNO) for the treatment of COVID-19 has not been well established.
OBJECTIVE: The primary objectives of this study are to observe the success of HFNO in preventing escalation to mechanical ventilation (MV) and to measure the prevalence of HFNO in King Abdulaziz Medical City (KAMC). The secondary objective is to describe patients who received HFNO clinically.
METHODS: This is a retrospective cohort study of all polymerase chain reaction (PCR)-confirmed COVID-19 patients who require oxygen therapy in KAMC, Jeddah between March 1st, 2020, and December 31st, 2020. Any patients requiring MV on admission were excluded.
RESULTS: 259 patients fit the inclusion criteria, and 25.5% of those included received HFNO. The number of non-survivors is 47 (18.1%). Mortality for HFNO, MV, and intensive care unit (ICU) are 30 (45.5%), 31 (60.8%), and 24 (32%), respectively. Their demographic was as follows; 160 were males, with a mean age of 60.93±15.01. Regarding the types of oxygen, low-flow nasal oxygen (LFNO) was administered to 243 out of the 259 patients, 66 received HFNO, 42 received MV, and 49 received other modes of ventilation. Additionally, 43.9% received HFNO escalated to MV. Patients who did not receive HFNO or MV were 178 (68.7%) in total.
CONCLUSIONS: The use of HFNO in COVID-19 patients could show better outcomes than MV in addition to preventing the use of MV. Larger studies are required to determine the efficacy of HFNO in COVID-19 patients.

UNASSIGNED: The role of corticosteroids in acute respiratory distress syndrome (ARDS) remains contentious. This study aims to investigate the prognostic significance of immune deficiency in patients with ARDS and its response to varying doses of corticosteroids.
UNASSIGNED: This single-center, retrospective cohort study enrolled 657 ARDS patients from January 24, 2008, to September 12, 2022, at Zhongshan Hospital of Fudan University, Shanghai, China. The patients were categorized into a discovery dataset (n=357) and a validation dataset (n=300), based on admission date. Further validation of the results in the validation dataset was used to enhance the credibility of the study conclusions. The study examined the association between immune deficiency and the patients\' clinical characteristics, treatment measures, and prognosis. The primary outcome was 28-day mortality post disease onset. Data analysis was conducted from June 15, 2023 to August 15, 2023.
UNASSIGNED: The initial risk factor analysis in the discovery dataset was primarily based on the clinical characteristics, and the results suggested that immune deficiency likely impacted overall survival among patients receiving different doses of corticosteroid treatment. Multivariate analysis identified immune deficiency as an independent prognostic factor for overall survival in both the discovery and validation datasets. The final analysis revealed that patients with mild to moderate ARDS [discovery dataset: hazard ratio (HR) =1.719; 95% confidence interval (CI): 1.229-2.406; log-rank test P=0.001; validation dataset: HR =1.874; 95% CI: 1.238-2.837; log-rank test P=0.002] or severe ARDS (discovery dataset: HR =1.874; 95% CI: 1.007-3.488; log-rank test P=0.04; validation dataset: HR =1.698; 95% CI: 1.042-2.768; log-rank test P=0.03) with immune deficiency exhibited lower overall survival rates. Patients with mild to moderate ARDS and immune deficiency showed greater benefits from low-dose corticosteroid treatment (HR =0.409; 95% CI: 0.249-0.671; P<0.001 for interaction), whereas those with severe ARDS and immune deficiency benefitted from both low and high-dose treatments (low corticosteroid: HR =0.299; 95% CI: 0.136-0.654; high corticosteroid: HR =0.458; 95% CI: 0.214-0.981; P=0.005 for interaction).
UNASSIGNED: Immune deficiency is an independent risk factor in ARDS. Incorporating it into the disease severity grading system based on the Berlin criteria may enhance personalized treatment approaches for ARDS patients. These findings warrant further validation through prospective, large-scale, multicenter randomized controlled trials (RCTs).

UNASSIGNED: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) therapy is being increasingly used as respiratory support for patients with severe coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). However, the long-term outcome of VV-ECMO as a bridge to lung transplantation in COVID-19-associated ARDS remains unclear, hence the purpose of this study aimed to evaluate its long-term outcome, safety, and feasibility.
UNASSIGNED: This was a retrospective cohort study from an institutional lung transplantation database between June 2020 and June 2022. Data on demographics, pre-transplantation laboratory values, postoperative outcomes, preoperative and postoperative transthoracic echocardiography findings, and survival rates were collected. Chi-square, Mann-Whitney U, Student\'s t, Kaplan-Meier, and Wilcoxon signed-rank tests were used for analysis.
UNASSIGNED: Twenty-five patients with COVID-19-associated ARDS underwent lung transplant surgery with VV-ECMO bridge. Unfortunately, six patients with COVID-19-associated ARDS using VV-ECMO died while waiting for transplantation during the same study period. Patients with VV-ECMO bridge were a more severe cohort than 16 patients without VV-ECMO bridge (lung allocation score: 88.1 vs. 74.9, P<0.001). These patients had longer intensive care unit and hospital stays (P=0.03 and P=0.02, respectively) and a higher incidence of complications after lung transplantation. The one-year survival rate of patients with VV-ECMO bridge was lower than that of patients without (78.3% vs. 100.0%, P=0.06), but comparable to that of patients with other lung transplant indications (84.2%, P=0.95). Echocardiography showed a decrease in the right ventricular systolic pressure (P=0.01), confirming that lung transplantation improved right heart function.
UNASSIGNED: Our findings suggest that VV-ECMO can be used to safely bridge patients with COVID-19 associated ARDS with right heart failure.

BACKGROUND: Sepsis is a dysregulated host immune response stemming from a systemic inflammatory response to microbial invasion, encompassing bacteria, viruses, and other pathogens. The vascular endothelial growth factor (VEGF) was initially identified for its potent induction of endothelial permeability. Studies have proposed a therapeutic role of dopamine in mitigating VEGF-induced permeability, shedding light on its potential in acute respiratory distress syndrome (ARDS) management.
OBJECTIVE: To determine the effect of dopamine as an inhibitor of VEGF and to prevent the progression of sepsis to acute lung injury (ALI) and ARDS.
METHODS: A total of 154 critical care unit patients with a diagnosis of sepsis were randomized into two groups: Group I (control group) and Group II (Study group). Both received standard treatment, as per ICU protocol. In addition, the study group (Group II) received a dopamine infusion of 2 micrograms/kg/min. Baseline routine investigation, procalcitonin, and chest X-ray were done. Day one and day seven blood samples were stored for analysis of VEGF levels. Murray\'s score and sequential organ failure assessment (SOFA) score (organ dysfunction) were calculated from day one to day seven.
RESULTS: VEGF levels on day seven were significantly lower in the study group compared to the control group (p<0.05). The PaO2/FiO2 ratio at day seven was significantly increased in the study group than in the control group, indicating an improvement in oxygenation status in the study group. There was a mean ICU stay of 9.3 days in the study group versus 11.6 days in the control group (p<0.05). The SOFA score showed a significant improvement in the study group from day five onwards, indicating a therapeutic effect of dopamine on organ dysfunction in sepsis.
CONCLUSIONS: Dopamine reduces VEGF and lung injury mediated by increased endothelial permeability.

BACKGROUND: Neutrophilic inflammation, characterized by dysregulated neutrophil activation, triggers a variety of inflammatory responses such as chemotactic infiltration, oxidative bursts, degranulation, neutrophil extracellular traps (NETs) formation, and delayed turnover. This type of inflammation is pivotal in the pathogenesis of acute respiratory distress syndrome (ARDS) and psoriasis. Despite current treatments, managing neutrophil-associated inflammatory symptoms remains a significant challenge.
OBJECTIVE: This review emphasizes the role of cyclin-dependent kinases (CDKs) in neutrophil activation and inflammation. It aims to highlight the therapeutic potential of repurposing CDK inhibitors to manage neutrophilic inflammation, particularly in ARDS and psoriasis. Additionally, it discusses the necessary precautions for the clinical application of these inhibitors due to potential off-target effects and the need for dose optimization.
UNASSIGNED: CDKs regulate key neutrophilic functions, including chemotactic responses, degranulation, NET formation, and apoptosis. Repurposing CDK inhibitors, originally developed for cancer treatment, shows promise in controlling neutrophilic inflammation. Clinical anticancer drugs, palbociclib and ribociclib, have demonstrated efficacy in treating neutrophilic ARDS and psoriasis by targeting off-label pathways, phosphoinositide 3-kinase (PI3K) and phosphodiesterase 4 (PDE4), respectively. While CDK inhibitors offer promising therapeutic benefits, their clinical repurposing requires careful consideration of off-target effects and dose optimization. Further exploration and clinical trials are necessary to ensure their safety and efficacy in treating inflammatory conditions.

OBJECTIVE: Human herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging and there is ongoing debate about its association with mortality and benefit of antiviral medication. We aimed to quantify the incidence and pathogenicity of pulmonary CMV and HSV reactivations in critically ill COVID-19 patients.
METHODS: Mechanically ventilated COVID-19 patients seropositive for CMV or HSV were included in this observational cohort study. Diagnostic bronchoscopy with bronchoalveolar lavage was performed routinely and analyzed for alveolar viral loads and inflammatory biomarkers. Utilizing joint modeling, we explored the dynamic association between viral load trajectories over time and mortality. We explored alveolar inflammatory biomarker dynamics between reactivated and non-reactivated patients.
RESULTS: Pulmonary reactivation (> 104 copies/ml) of CMV occurred in 6% of CMV-seropositive patients (9/156), and pulmonary reactivation of HSV in 37% of HSV-seropositive patients (63/172). HSV viral load dynamics prior to or without antiviral treatment were associated with increased 90-day mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.04-1.47). The alveolar concentration of several inflammatory biomarkers increased with HSV reactivation, including interleukin (IL)-6, IL-1β, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF).
CONCLUSIONS: In mechanically ventilated COVID-19 patients, HSV reactivations are common, while CMV reactivations were rare. HSV viral load dynamics prior to or without antiviral treatment are associated with mortality. Alveolar inflammation is elevated after HSV reactivation.

BACKGROUND: Despite the significance and prevalence of acute respiratory distress syndrome (ARDS), its detection remains highly variable and inconsistent. In this work, we aim to develop an algorithm (ARDSFlag) to automate the diagnosis of ARDS based on the Berlin definition. We also aim to develop a visualization tool that helps clinicians efficiently assess ARDS criteria.
METHODS: ARDSFlag applies machine learning (ML) and natural language processing (NLP) techniques to evaluate Berlin criteria by incorporating structured and unstructured data in an electronic health record (EHR) system. The study cohort includes 19,534 ICU admissions in the Medical Information Mart for Intensive Care III (MIMIC-III) database. The output is the ARDS diagnosis, onset time, and severity.
RESULTS: ARDSFlag includes separate text classifiers trained using large training sets to find evidence of bilateral infiltrates in radiology reports (accuracy of 91.9%±0.5%) and heart failure/fluid overload in radiology reports (accuracy 86.1%±0.5%) and echocardiogram notes (accuracy 98.4%±0.3%). A test set of 300 cases, which was blindly and independently labeled for ARDS by two groups of clinicians, shows that ARDSFlag generates an overall accuracy of 89.0% (specificity = 91.7%, recall = 80.3%, and precision = 75.0%) in detecting ARDS cases.
CONCLUSIONS: To our best knowledge, this is the first study to focus on developing a method to automate the detection of ARDS. Some studies have developed and used other methods to answer other research questions. Expectedly, ARDSFlag generates a significantly higher performance in all accuracy measures compared to those methods.

Leptospirosis, a zoonotic disease caused by spirochetes of the genus Leptospira, poses unique challenges in pregnancy due to its varied clinical presentation and potential adverse outcomes for both mother and fetus. We present a case of a 24-year-old primigravida at 35 weeks of gestation who presented with fever, dyspnea, and abdominal pain, and was ultimately diagnosed with leptospirosis complicated by acute respiratory distress syndrome (ARDS). Prompt initiation of antibiotic therapy, supportive care, and timely delivery via emergency cesarean section led to favorable maternal and neonatal outcomes. This case report underscores the importance of considering leptospirosis in pregnant patients presenting with similar symptoms, particularly in endemic regions, and highlights the critical role of multidisciplinary management in optimizing outcomes.

Pulmonary edema is a rare mechanism of death that develops after partial hanging, a potential complication that physicians should consider early in the management of these patients. This case series discusses the presentation, evaluation, and treatment course of three patients who had attempted suicide by hanging and were admitted to the hospital. These patients were admitted to the intensive care unit after being stabilized and supportive treatment was provided. In all the cases, a radiological scan of the chest revealed diffuse infiltrates consistent with pulmonary edema on both sides, features of which were also noted during a diagnostic bronchoscopy. After providing the best intensive care in the hospital, two patients clinically improved, and one patient succumbed to cardiac arrest. As most patients will be brought dead to the hospital following hanging, negative pressure pulmonary edema remains underdiagnosed. Thus, this case series enumerates the possible etiologies of negative pressure pulmonary edema and its contribution to death following suicidal hanging.