Macrophage Activation Syndrome in Coinciding Pandemics of Obesity and COVID-19: Worse than Bad.

Epigenetic changes have long-lasting impacts, which influence the epigenome and are maintained during cell division. Thus, human genome changes have required a very long timescale to become a major contributor to the current obesity pandemic. Whereas bidirectional effects of coronavirus disease 2019 (COVID-19) and obesity pandemics have given the opportunity to explore, how the viral microribonucleic acids (miRNAs) use the human's transcriptional machinery that regulate gene expression at a posttranscriptional level. Obesity and its related comorbidity, type 2 diabetes (T2D), and new-onset diabetes due to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are additional risk factors, which increase the severity of COVID-19 and its related mortality. The higher mortality rate of these patients is dependent on severe cytokine storm, which is the sum of the additional cytokine production by concomitant comorbidities and own cytokine synthesis of COVID-19. Patients with obesity facilitate the SARS-CoV-2 entry to host cell via increasing the host's cell receptor expression and modifying the host cell proteases. After entering the host cells, the SARS-CoV-2 genome directly functions as a messenger ribonucleic acid (mRNA) and encodes a set of nonstructural proteins via processing by the own proteases, main protease (Mpro), and papain-like protease (PLpro) to initiate viral genome replication and transcription. Following viral invasion, SARS-CoV-2 infection reduces insulin secretion via either inducing ß-cell apoptosis or reducing intensity of angiotensin-converting enzyme 2 (ACE2) receptors and leads to new-onset diabetes. Since both T2D and severity of COVID-19 are associated with the increased serum levels of pro-inflammatory cytokines, high glucose levels in T2D aggravate SARS-CoV-2 infection. Elevated neopterin (NPT) value due to persistent interferon gamma (IFN-γ)-mediated monocyte-macrophage activation is an indicator of hyperactivated pro-inflammatory phenotype M1 macrophages. Thus, NPT could be a reliable biomarker for the simultaneously occurring COVID-19-, obesity- and T2D-induced cytokine storm. While host miRNAs attack viral RNAs, viral miRNAs target host transcripts. Eventually, the expression rate and type of miRNAs also are different in COVID-19 patients with different viral loads. It is concluded that specific miRNA signatures in macrophage activation phase may provide an opportunity to become aware of the severity of COVID-19 in patients with obesity and obesity-related T2D.

Disseminated Varicella-Zoster Virus Presenting With Pneumonitis and Diffuse Alveolar Hemorrhage in an Immunocompetent Patient.

Varicella pneumonitis is typically seen in individuals with risk factors such as male gender, smoking history, and immunocompromised state and is often associated with disseminated infection, whereas primary varicella-zoster virus (VZV) infection usually involves a diffuse vesicular rash and rarely progresses to viral pneumonia. VZV pneumonitis accompanied by disseminated VZV infection is associated with a high mortality rate and may progress to diffuse alveolar hemorrhage in severe cases. In addition to cutaneous lesions, patients typically develop dyspnea, cough, tachypnea, chest pain, fever, and hemoptysis. Here, we present a rare case of disseminated VZV infection in an immunocompetent patient with pneumonitis and diffuse alveolar hemorrhage.

Dose-response relationship between awake prone-positioning duration and PaO2/FiO2 changes and risk of disease aggravation in patients with severe COVID-19: A prospective cohort study.

BACKGROUND: Patients not mechanically ventilated often fail to achieve the recommended duration of awake prone positioning due to treatment interruption and discomfort. Few studies have investigated the link between treatment outcome and prone-positioning duration, the inability to accurately guide patients to perform awake prone positioning. OBJECTIVES: The aim of this study was to characterise and explore the relationship between awake prone-positioning duration with the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2 [P/F]) changes and the risk of disease aggravation. METHODS: A prospective cohort study; dose-response relationship was used. Awake prone positioning was performed on patients with severe Corona Virus Disease 2019 (COVID-19) for 5 consecutive days from 1 February to 21 March 2023. Linear and logistic regression models were utilised to assess the association between prone-positioning duration with P/F changes and risk of disease aggravation, respectively. Meanwhile, the restricted cubic spline was used to evaluate the dose-response relationships. RESULTS: A total of 408 patients with severe COVID-19 were analysed. The daily prone positioning duration was 4.57 ± 2.74 h/d, and the changes in P/F were 67.63 ± 69.17 mmHg. On the sixth day of hospitalisation, the condition of 52 (12.8%) patients deteriorated. There was a positive, nonlinear dose-response relationship (Poverall < 0.001, Pnonlinearity = 0.041) and a strong, significant positive correlation (ß = 29.286, t = 4.302, P < 0.001) between the prone-positioning duration and P/F changes. The risk of disease aggravation gradually decreases with the increase of prone-positioning duration. Nonetheless, the prone-positioning duration was not statistically associated with disease aggravation (odds ratio = 0.986, 95% confidence interval: 0.514-1.895). CONCLUSIONS: Awake prone positioning for ≥4 h/d is effective on oxygenation (not mortality/intubation) and is achievable for patients with severe COVID-19. Prolonged prone positioning is promising in improving patients' oxygenation but does not alleviate their risk of disease aggravation.

Efficacy and safety of early prone position in postoperative cardiac surgery adults with acute respiratory distress syndrome: a single-center retrospective cohort study.

Background: Acute respiratory distress syndrome (ARDS) is a leading cause of postoperative respiratory failure after cardiac surgery, and the mortality rate is extremely high. Although prone positioning (PP) may be safe and effective for ARDS, it is still not widely adopted in cardiac surgery patients. We aimed to assess the efficacy and safety of early PP in ARDS after cardiac surgery. Methods: This is a single-center retrospective cohort study. We included adult intensive care unit (ICU) patients who developed ARDS with arterial pressure of oxygen to fraction of oxygen ratio (P/F) ≤200 mmHg within 72 hours after cardiac surgery between 1 January 2019 and 1 August 2023. The outcomes were P/F after 1 session of PP, duration of mechanical ventilation (MV) and ICU stay, and adverse events. Results: In total, 79 patients who underwent PP and 87 patients who underwent supine position (SP) were included. The mean time to perform PP after ICU admission was 38.0 hours. The P/F improved significantly after 1 session of PP treatment [160.0 (127.8-184.3) vs. 275.0 (220.0-325.0) mmHg, P<0.001], the duration of MV and ICU stay in the PP group were significantly shorter than those in the SP group [84.0 (64.0-122.0) vs. 120.0 (97.0-182.0) h, P<0.001; 6.0 (5.0-8.0) vs. 8.0 (6.0-12.0) days, P<0.001, respectively]. No adverse events were observed during the PP even in patients with intra-aortic balloon pump (IABP). Conclusions: Early PP treatment is effective and safe for patients with moderate to severe ARDS after cardiac surgery and it is even safe in a subgroup placed with IABP.

Contrasting predictors of severe primary graft dysfunction following transplant for chronic and acute respiratory failure.

Background: Lung transplantation represents a pivotal intervention for individuals grappling with end-stage lung diseases, and the role of lung transplantation in acute respiratory distress syndrome (ARDS) patients has garnered increased attention especially after the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have demonstrated a high incidence of primary graft dysfunction (PGD) in patients with ARDS compared to contemporaneous controls undergoing transplantation for chronic end-stage lung diseases although underlying mechanisms or risk factors remain unknown. This retrospective study investigates the contrasting risk factors for PGD grade 3 in patients with ARDS and chronic respiratory failure undergoing lung transplantation. Methods: The study included 293 patients who underwent lung transplantation from January 2018 through June 2023. We performed a multivariate logistic regression analysis using variables from the univariate logistic regression analyses to predict PGD grade 3. Results: Our findings reveal distinct predictors for PGD grade 3 in the two cohorts. ARDS patients had higher incidence of PGD grade 3 than non-ARDS patients (30.2% vs. 9.6%, P<0.001). Multivariate logistic regression analysis showed ischemic time [odds ratio (OR) =0.60; 95% confidence interval (CI): 0.40-0.90; P=0.01] as predictor of PGD grade 3 for non-ARDS patients, and age (OR =0.72; 95% CI: 0.52-0.99; P=0.048), pre-operative albumin (OR <0.01; 95% CI: <0.01-0.74; P=0.042) for ARDS patients. Interestingly, there was no notable difference in post-transplant survival between the two groups. Conclusions: This study highlights differing risk profiles for severe PGD in ARDS and non-ARDS lung transplant recipients, underscoring the need for tailored approaches in managing these patients. It paves the way for further research to refine strategies aimed at reducing PGD incidence and enhancing transplant outcomes in these distinct populations.

A tidal volume of 7 mL/kg PBW or higher may be safe for COVID-19 patients.

PURPOSE: The novel coronavirus disease (COVID-19) has revived the debate on the optimal tidal volume during acute respiratory distress syndrome (ARDS). Some experts recommend 6 mL/kg of predicted body weight (PBW) for all patients, while others suggest 7-9 mL/kg PBW for those with compliance >50 mL/cmH2O. We investigated whether a tidal volume ≥ 7 ml/kg PBW may be safe in COVID-19 patients, particularly those with compliance >50 mL/cmH2O. MATERIALS AND METHODS: This secondary analysis of a multicenter study compares the Intensive Care Unit (ICU) mortality among 600 patients ventilated with <7 or ≥ 7 mL/kg PBW. Compliance was categorized as <40, 40-50, or > 50 mL/cmH2O. RESULTS: 346 patients were ventilated with <7 (6.2 ± 0.5) mL/kg PBW and 254 with ≥7 (7.9 ± 0.9) mL/kg PBW. ICU mortality was 33 % and 29 % in the two groups (p = 0.272). At multivariable regression analysis, tidal volume ≥ 7 mL/kg PBW was associated with lower ICU mortality in the overall population (odds ratio: 0.62 [95 %-confidence interval: 0.40-0.95]) and in each compliance category. CONCLUSIONS: A tidal volume ≥ 7 (up to 9) mL/kg PBW was associated with lower ICU mortality in these COVID-19 patients, including those with compliance <40 mL/cmH2O. This finding should be interpreted cautiously due to the retrospective study design. TRIAL REGISTRATION: ClinicalTrails.govNCT04388670.

Mitochondrial transplantation attenuates lipopolysaccharide-induced acute respiratory distress syndrome.

BACKGROUND: The mitochondria are essential organelles not only providing cellular energy in the form of ATP, but also regulating the inflammatory response and the cell death program. Mitochondrial dysfunction has been associated with various human diseases, including metabolic syndromes as well as inflammatory and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by uncontrolled alveolar inflammation, apoptotic lung epithelial/endothelial cells, and pulmonary edema. Despite the high mortality of ARDS, an effective pharmacotherapy to treat this disease has not been established yet. Therefore, identifying a novel targeted therapy for ARDS is important. Recently, exogenous mitochondrial transplantation was reported to be beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transplantation on ARDS in vitro and in vivo. METHODS: Mitochondria were isolated from human stem cells. For in vitro efficacy of mitochondrial transplantation on the inflammation and cell death, murine alveolar macrophages MH-S and human pulmonary microvascular endothelial cells HPMECs were exposed to LPS, respectively. The ARDS mice model established by a single intratracheal instillation of LPS was used for in vivo efficacy of intravenously treated mitochondria. RESULTS: Our results showed that the mitochondria isolated from human stem cells exhibited an anti-inflammatory effect against alveolar macrophages and an anti-apoptotic effect against the alveolar epithelial cells. Furthermore, intravenous mitochondrial treatment was associated with the attenuation of lung injury in the LPS-induced ARDS mice. CONCLUSION: Dual effects of mitochondria on anti-inflammation and anti-apoptosis support the potential of mitochondrial transplantation as a novel therapeutic strategy for ARDS.

Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.

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. AIM OF REVIEW: 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. KEY SCIENTIFIC CONCEPTS OF REVIEW: 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.

Clinical Characteristics and Risk Factors of Mechanical Ventilation Among COVID-19 Patients on High-Flow Nasal Oxygen (HFNO).

INTRODUCTION: 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. OBJECTIVES: 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. CONCLUSION: 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.

Effect of Dopamine as a Vascular Endothelial Growth Factor Antagonist on the Development of Acute Lung Injury in Sepsis Patients.

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. MAIN 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. CONCLUSION: Dopamine reduces VEGF and lung injury mediated by increased endothelial permeability.

From Cosmetic Surgery to Critical Care: Clinical Mimicry of Acute Respiratory Distress Syndrome Following Gluteal Augmentation Surgery.

Gluteal augmentation surgery, commonly known as the Brazilian Butt Lift (BBL), has become increasingly popular and is offered at numerous surgical centers. Typically performed on an outpatient basis, the procedure takes less than four hours, making it an appealing option for many patients. However, BBL is associated with multiple complications, some of which can be severe, resulting in high mortality rates. Most such post-operative adverse events necessitate urgent transfer to hospitals for optimal care, with post-operative respiratory distress being one such critical sign. Fat embolism syndrome (FES) is a notable complication of BBL. The diagnosis of FES is primarily clinical, supported by imaging studies such as chest X-rays and CT scans. FES often goes underdiagnosed due to the lack of definitive diagnostic criteria and its clinical and radiological similarities to other conditions. Despite its underdiagnosis, FES is reported in approximately 0.06% of patients undergoing BBL. Failure to diagnose it early can lead to complications from empiric treatment of other suspected conditions, potentially worsening the prognosis. Our patient developed respiratory failure within an hour after undergoing BBL. The time to symptom onset and the patient's agitation before the respiratory episode broadened the differential for her condition. This case report highlights the importance of recognizing FES and exploring potential preventive measures, including advancements in surgical techniques and prophylactic strategies.

Association of immune deficiency with prognosis and corticosteroid treatment benefits among patients with acute respiratory distress syndrome.

Background: 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. Methods: 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. Results: 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). Conclusions: 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).

Impact of bridging veno-venous extracorporeal membrane oxygenation to COVID-19 lung transplantation.

Background: 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. Methods: 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. Results: 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. Conclusions: Our findings suggest that VV-ECMO can be used to safely bridge patients with COVID-19 associated ARDS with right heart failure.

Learning using privileged information with logistic regression on acute respiratory distress syndrome detection.

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.

Pulmonary herpes simplex virus and cytomegalovirus in patients with acute respiratory distress syndrome related to COVID-19.

PURPOSE: 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-1ß, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF). CONCLUSION: 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.

Unmasking Negative Pressure Pulmonary Edema Following Hanging: A Case Series.

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.

Leptospirosis-Associated Acute Respiratory Distress Syndrome (ARDS) in Pregnancy: A Rare Presentation.

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.

ARDSFlag: an NLP/machine learning algorithm to visualize and detect high-probability ARDS admissions independent of provider recognition and billing codes.

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. CONCLUSION: 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.

Effect of apigetrin in pseudo-SARS-CoV-2-induced inflammatory and pulmonary fibrosis in vitro model.

SARS-CoV-2 has become a global public health problem. Acute respiratory distress syndrome (ARDS) is the leading cause of death due to the SARS-CoV-2 infection. Pulmonary fibrosis (PF) is a severe and frequently reported COVID-19 sequela. In this study, an in vitro model of ARDS and PF caused by SARS-CoV-2 was established in MH-S, THP-1, and MRC-5 cells using pseudo-SARS-CoV-2 (PSCV). Expression of proinflammatory cytokines (IL-6, IL-1ß, and TNF-α) and HIF-1α was increased in PSCV-infected MH-S and THP-1 cells, ARDS model, consistent with other profiling data in SARS-CoV-2-infected patients have been reported. Hypoxia-inducible factor-1 alpha (HIF-1α) siRNA and cobalt chloride were tested using this in vitro model. HIF-1α knockdown reduces inflammation caused by PSCV infection in MH-S and THP-1 cells and lowers elevated levels of CTGF, COLA1, and α-SMA in MRC-5 cells exposed to CPMSCV. Furthermore, apigetrin, a glycoside bioactive dietary flavonoid derived from several plants, including Crataegus pinnatifida, which is reported to be a HIF-1α inhibitor, was tested in this in vitro model. Apigetrin significantly reduced the increased inflammatory cytokine (IL-6, IL-1ß, and TNF-α) expression and secretion by PSCV in MH-S and THP-1 cells. Apigetrin inhibited the binding of the SARS-CoV-2 spike protein RBD to the ACE2 protein. An in vitro model of PF induced by SARS-CoV-2 was produced using a conditioned medium of THP-1 and MH-S cells that were PSCV-infected (CMPSCV) into MRC-5 cells. In a PF model, CMPSCV treatment of THP-1 and MH-S cells increased cell growth, migration, and collagen synthesis in MRC-5 cells. In contrast, apigetrin suppressed the increase in cell growth, migration, and collagen synthesis induced by CMPSCV in THP-1 and MH-S MRC-5 cells. Also, compared to control, fibrosis-related proteins (CTGF, COLA1, α-SMA, and HIF-1α) levels were over two-fold higher in CMPSV-treated MRC-5 cells. Apigetrin decreased protein levels in CMPSCV-treated MRC-5 cells. Thus, our data suggest that hypoxia-inducible factor-1 alpha (HIF-1α) might be a novel target for SARS-CoV-2 sequela therapies and apigetrin, representative of HIF-1alpha inhibitor, exerts anti-inflammatory and PF effects in PSCV-treated MH-S, THP-1, and CMPVSC-treated MRC-5 cells. These findings indicate that HIF-1α inhibition and apigetrin would have a potential value in controlling SARS-CoV-2-related diseases.

Extensive Thrombosis in Catastrophic Antiphospholipid Syndrome in a Newly Diagnosed Systemic Lupus Erythematosus: A Case Report.

In this case report, we present the development of catastrophic antiphospholipid syndrome (CAPS), a rare and potentially fatal consequence of systemic lupus erythematosus (SLE), in a 33-year-old Micronesian woman. CAPS is characterized by extensive arterial thrombosis and multiorgan failure. The patient first showed signs of neuropsychiatric symptoms, brain infarctions on imaging, and severe hypoxic respiratory failure brought into the hospital by diffuse alveolar hemorrhage (DAH) along with lupus nephritis (LN). Blood urea nitrogen (BUN) and creatinine (Cr) were progressively elevated to 102/4.1 mg/dL, respectively. A urinalysis revealed microscopic hematuria and proteinuria with a urine protein/creatinine ratio of 6052 mg/g. She was also found to have had microangiopathic hemolytic anemia (MAHA) and severe venous thrombosis, both of which were indicative of CAPS. An aggressive approach, including immunosuppressive medication, therapeutic plasma exchange, and anticoagulation, had positive results, including renal recovery and the cessation of thrombotic episodes. This instance highlights how crucial it is to identify CAPS patients early and take appropriate action to improve patient outcomes for this difficult and sometimes deadly disorder.