Hydroxychloroquine attenuates sepsis-induced acute respiratory distress syndrome in rats.

BACKGROUND: This study investigates the effects of hydroxychloroquine (HCQ) on a sepsis-induced acute respiratory distress syndrome (ARDS) model in rats, initiated by a fecal intraperitoneal injection procedure (FIP). METHODS: Three groups were established: control (n=8), FIP + saline (n=7), and FIP + HCQ (20 mg/kg/day) (n=9). Blood samples were collected for arterial blood gas and biochemical analyses, and bilateral pneumonectomy was performed for histopathologic examination. RESULTS: In the FIP + saline group, PaO2 decreased and PaCO2 increased, whereas these levels normalized in the FIP + HCQ group compared to the control (p<0.001 and p<0.05, respectively). Histopathological scores for alveolar congestion, perivascular/interstitial edema, hemorrhage in alveolar tissue, leukocyte infiltration or aggregation in air spaces/vascular walls, and alveolar wall/hyaline membrane thickness increased in the FIP + saline group compared to the control group (p<0.01). These scores decreased in the FIP + HCQ group compared to the FIP + saline group (p<0.01). HCQ reversed the sepsis-induced increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and lactic acid. CONCLUSION: HCQ may be an effective and safe option to mitigate the severe progression of ARDS.

A SEVERE CASE OF NON TYPHOIDAL SALMONELLA ASSOCIATED WITH MULTIPLE ORGAN DAMAGE- CASE STUDY AND LITERATURE REVIEW.

We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient's condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.

[Clinical characteristics and prognosis of acute gastrointestinal injury in patients with sepsis-associated acute respiratory distress syndrome].

OBJECTIVE: To observe the clinical characteristics and prognosis of patients with acute respiratory distress syndrome (ARDS) in sepsis combined with acute gastrointestinal injury (AGI) of different grades, and to further explore the risk factors associated with the poor prognosis of patients. METHODS: The clinical data of patients with septic ARDS admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from March to October 2023 were collected. According to the 2012 European Association of Critical Care Medicine AGI definition and grading criteria, the patients were categorized into AGI grade 0- IV groups. The clinical characteristics and 28-day clinical outcomes of the patients were observed; the risk factors related to the prognosis of patients with septic ARDS combined with AGI were analyzed by using univariate and multivariate Logistic regression; and the receiver operator characteristic curve (ROC curve) and calibration curves were plotted to evaluate the predictive value of each risk factor on the prognosis of patients with septic ARDS combined with AGI. RESULTS: A total of 92 patients with septic ARDS were enrolled, including 7 patients in the AGI 0 group, 20 patients in the AGI I group, 38 patients in the AGI II group, 23 patients in the AGI III group, and 4 patients in the AGI IV group. The incidence of AGI was 92.39%. With the increase of AGI grade, the ARDS grade increased, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), intra-abdominal pressure (IAP), white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), lymphocyte percentage (LYM%), and 28-day mortality all showed a significant increasing trend, while the oxygenation index (PaO2/FiO2) showed a significant decreasing trend (all P < 0.05). Pearson correlation analysis showed that APACHE II score, SOFA score, and ARDS classification were positively correlated with patients' AGI grade (Pearson correlation index was 0.386, 0.473, and 0.372, respectively, all P < 0.001), and PaO2/FiO2 was negatively correlated with patients' AGI grade (Pearson correlation index was -0.425, P < 0.001). Among the patients with septic ARDS combined with AGI, there were 68 survivors and 17 deaths at 28 days. The differences in APACHE II score, SOFA score, ARDS grade, AGI grade, PaO2/FiO2, IAP, AGI 7-day worst value, length of ICU stay, and total length of hospital stay between the survival and death groups were statistically significant. Univariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.350, 95% confidence interval (95%CI) was 1.071-1.702, P = 0.011], PaO2/FiO2 (OR = 0.964, 95%CI was 0.933-0.996, P = 0.027) and AGI 7-day worst value (OR = 2.103, 95%CI was 1.194-3.702, P = 0.010) were the risk factors for 28-day mortality in patients with septic ARDS combined with AGI. Multivariate Logistic regression analysis showed that SOFA score (OR = 1.384, 95%CI was 1.153-1.661, P < 0.001), PaO2/FiO2 (OR = 0.983, 95%CI was 0.968-0.999, P = 0.035) and AGI 7-day worst value (OR = 1.992, 95%CI was 1.141-3.478, P = 0.015) were the independent risk factors for 28-day mortality in patients with septic ARDS combined with AGI. ROC curve analysis showed that SOFA score, PaO2/FiO2 and AGI 7-day worst value had predictive value for the 28-day prognosis of patients with septic ARDS combined with AGI. The area under the ROC curve (AUC) was 0.824 (95%CI was 0.697-0.950), 0.760 (95%CI was 0.642-0.877) and 0.721 (95%CI was 0.586-0.857), respectively, all P < 0.01; when the best cut-off values of the above metrics were 5.50 points, 163.45 mmHg (1 mmHg≈0.133 kPa), and 2.50 grade, the sensitivities were 94.1%, 94.1%, 31.9%, respectively, and the specificities were 80.9%, 67.6%, 88.2%, respectively. CONCLUSIONS: The incidence of AGI in patients with septic ARDS is about 90%, and the higher the AGI grade, the worse the prognosis of the patients. SOFA score, PaO2/FiO2 and AGI 7-day worst value have a certain predictive value for the prognosis of patients with septic ARDS combined with AGI, among which, the larger the SOFA score and AGI 7-day worst value, and the smaller the PaO2/FiO2, the higher the patients' mortality.

Severe Fatal ARDS Due to Untreated Human Granulocytic Anaplasmosis in a 67-Year-Old Man: A Case Report.

BACKGROUND Anaplasmosis, or human granulocytic anaplasmosis (HGA), is a tick-borne diseased caused by a gram-negative, intracellular bacterium, Anaplasma phagocytophilum. HGA usually presents with mild symptoms but can be more severe. This report describes a 67-year-old male resident of rural Pennsylvania, admitted to the hospital after a fall, who developed fatal acute respiratory distress syndrome (ARDS) associated with human granulocytic anaplasmosis (HGA) following transmission of Anaplasma phagocytophilum by a tick bite (Ixodes scapularis). CASE REPORT A 67-year-old man, resident of rural Pennsylvania, with history of diabetes mellitus, presented after falling from a 7-foot-tall ladder, sustaining right-sided hemopneumothorax, multiple right rib fractures, and unstable T12 vertebra fracture. He required tube thoracostomy and underwent T9-L2 posterior spinal fusion surgery. His initial labs showed leukopenia, thrombocytopenia, and elevated transaminase levels. His course was complicated by cardiac arrest and acute respiratory failure, consistent with severe ARDS. He received high positive end-expiratory pressure (PEEP) ventilation, prone positioning, and neuromuscular paralysis to improve refractory hypoxemia. Bronchoalveolar lavage (BAL) for bacterial, fungal, viral pathogens, Covid-19, respiratory viral panel, Mycoplasma pneumoniae, and Chlamydia pneumoniae were negative. his family withdrew medical care, knowing the patient's own wishes, and the patient died. Polymerase chain reaction (PCR) for Anaplasma DNA came back positive after the patient's death. His peripheral smear was then examined, showing morulae inside the cytoplasm of infected neutrophils.   CONCLUSIONS This report describes the atypical presentation of a case of HGA and highlights that in parts of the world where tick-borne diseases are endemic, disease awareness, high index of clinical suspicion, and early diagnosis and management are required.

Systemic Corticosteroid as an Adjunct for Acute Respiratory Distress Syndrome in Non-Fatal Fresh Water Drowning: An Evidence-based Case Report.

BACKGROUND: Acute lung injury or acute respiratory distress syndrome (ARDS) is one of the most common complications of non-fatal drowning. Although respiratory societies' guidelines endorse the role of systemic corticosteroids in ARDS, the evidence for systemic corticosteroid use in ARDS due to non-fatal drowning is limited. METHODS: A search was conducted on Pubmed, OVID, and EuropePMC, assessing the clinical question using inclusion and exclusion criteria. The selected studies were critically appraised, and the results were summarized. RESULTS: A total of six retrospective studies were selected and assessed, all studies showed poor validity and a high risk of bias. Out of six studies, only four informed us of steroid administration's effect on outcomes. In two studies, mortality associated with corticosteroid administration seemed to be higher. On the contrary, one study found no mortality in the corticosteroid group, but 100% mortality was observed in the control group. In another study, steroid therapy seemed to not affect hospital length of stay or mechanical ventilation rates. CONCLUSION: Corticosteroid administration for non-fatal drowning and its impact on clinical outcomes remains equivocal. Routine administration of corticosteroids is not indicated and should be done on a case-by-case basis.

Clinical outcomes of corticosteroid administration for acute respiratory distress syndrome in adults based on meta-analyses and trial sequential analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and is responsible for a high worldwide mortality rate. OBJECTIVE: Investigate whether corticosteroids could benefit clinical outcomes in adult with ARDS. METHODS: A comprehensive search of electronic databases Ovid MEDLINE, Ovid EMbase, and Cochrane Library from their inception to 7 May 2023 was conducted to identify studies that met the eligibility criteria, including only randomized controlled trials. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the methods of trial sequential analysis. MAIN OUTCOME MEASURES: Mortality rates, including including the 14-, 28-, 45-, and 60-day mortality, hospital mortality, and intensive care unit (ICU) mortality. SAMPLE SIZE: 17 studies with 2508 patients. RESULTS: Data relating to mortality at 14, 28, 45, and 60 days were not significantly different when treatments with corticosteroids and placebo were compared. In terms of hospital and ICU mortality, the mortality of those who had received corticosteroids was significantly lower than that of those who had not. ARDS patients who received assisted ventilation benefited from corticosteroid therapy, as revealed by the significant difference in outcome days between those who received assisted ventilation and those who did not. Corticosteroid had significantly more days free from mechanical ventilation, ICU-free days, and MODS-free days during the first 28 days, but not more organ support-free days up to day 28. CONCLUSION: Although corticosteroid therapy did not reduce mortality rates at different observation periods, it significantly reduced hospital and ICU mortality. Administering corticosteroids to ARDS patients significantly decreased the days of assisted ventilation and time cost consumption. This study confirmed that long-term use of low-dose glucocorticoids may have a positive effect on early ARDS. LIMITATION: Risk of bias due to the differences in patient characteristics.

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.

Veno-venous extracorporeal membrane oxygenation for perioperative management of infective endocarditis after COVID-19 with acute respiratory distress syndrome: a case report.

BACKGROUND: Infective endocarditis (IE) is a rare cardiovascular complication in patients with coronavirus disease 2019 (COVID-19). IE after COVID-19 can also be complicated by acute respiratory distress syndrome (ARDS); however, the guidelines for the treatment of such cases are not clear. Here, we report a case of perioperative management of post-COVID-19 IE with ARDS using veno-venous extracorporeal membrane oxygenation (V-V ECMO). CASE PRESENTATION: The patient was a 40-year-old woman who was admitted on day 18 of COVID-19 onset and was administered oxygen therapy, remdesivir, and dexamethasone. The patient's condition improved; however, on day 24 of hospitalization, the patient developed hypoxemia and was admitted to the intensive care unit (ICU) due to respiratory failure. Blood culture revealed Corynebacterium striatum, and transesophageal echocardiography revealed vegetation on the aortic and mitral valves. Valve destruction was mild, and the cause of respiratory failure was thought to be ARDS. Despite continued antimicrobial therapy, ARDS did not improve the patient's condition, and valve destruction progressed; therefore, surgical treatment was scheduled on day 13 of ICU admission. After preoperative consultation with the team, a decision was made to initiate V-V ECMO after the patient was weaned from CPB, with concerns about further worsening of her respiratory status after surgery. The patient returned to the ICU with transition to V-V ECMO, and her circulation remained stable. The patient was weaned off V-V ECMO on postoperative day 33 and discharged from the ICU on postoperative day 47. CONCLUSIONS: ARDS may occur in patients with IE after COVID-19. Owing to concerns about further exacerbation of pulmonary damage, the timing of surgery should be comprehensively considered. Preoperatively, clinicians should discuss perioperative ECMO introduction and configuration.

Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery.

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12-48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.

Hypoxemia and its clinical predictors among children with respiratory distress admitted to the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

INTRODUCTION: Hypoxemia is a common complication of childhood respiratory tract infections and non-respiratory infections. Hypoxemic children have a five-fold increased risk of death compared to children without hypoxemia. In addition, there is limited evidence about hypoxemia and clinical predictors in Ethiopia. Therefore, this study was conducted to assess the prevalence and clinical predictors of hypoxemia among children with respiratory distress admitted to the University of Gondar Comprehensive Specialized Hospital. METHODS: An institutional-based cross-sectional study was conducted from December 2020 to May 2021 in northwest Ethiopia. A total of 399 study participants were selected using systematic random sampling. The oxygen saturation of the child was measured using Masimo rad-5 pulse oximetry. SPSS version 21 software was used for statistical analysis. RESULT: In this study, the prevalence of hypoxemia among children with respiratory distress was 63.5%. The clinical signs and symptoms significantly associated with hypoxemia were: head-nodding (AOR: 4.1, 95% CI: 1.81-9.28) and chest indrawing (AOR: 3.08, 95% CI: 1.32-7.16) which were considered statistically the risk factors for hypoxemia while inability to feed (AOR: 0.13, 95% CI: 0.02-0.77) was the protective factor for hypoxemia. The most sensitive predictors of hypoxemia were fast breathing with sensitivity (98.4%), nasal flaring (100.0%), chest indrawing (83.6%), and intercostal retraction (93.1%). The best specific predictors of hypoxemia were breathing difficulty with specificity (79.4%), inability to feed (100.0%), wheezing (83.0%), cyanosis (98.6%), impaired consciousness (94.2%), head-nodding (88.7%), and supra-sternal retraction (96.5%). CONCLUSION AND RECOMMENDATION: The prevalence of hypoxemia among children was high. The predictors of hypoxemia were the inability to feed, head nodding, and chest indrawing. It is recommended that the health care settings provide immediate care for the children with an inability to feed, head nodding, and chest indrawing. The policymakers better to focus on preventive strategies, particularly those with the most specific clinical predictors.

[COVID-19 in the intensive care unit]. / Intensivmedizinische Therapie von COVID-19.

The acute respiratory failure as well as ARDS (acute respiratory distress syndrome) have challenged clinicians since the initial description over 50 years ago. Various causes can lead to ARDS and therapeutic approaches for ARDS/ARF are limited to the support or replacement of organ functions and the prevention of therapy-induced consequences. In recent years, triggered by the SARS-CoV-2 pathogen, numerous cases of acute lung failure (C-ARDS) have emerged. The pathophysiological processes of classical ARDS and C-ARDS are essentially similar. In their final stages of inflammation, both lead to a disruption of the blood-air barrier. Treatment strategies for C-ARDS, like classical ARDS, focus on supporting or replacing organ functions and preventing consequential damage. This article summarizes the treatment strategies in the intensive care unit.

Exogenous surfactant for lung contusion causing ARDS: A systematic review of clinical and experimental reports.

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.

The impact and validity of the Berlin criteria on burn-induced ARDS: Examining mortality rates, and inhalation injury influences. A single center observational cohort study.

BACKGROUND: As several recent studies have shown low mortality rates in burn injury induced ARDS early (≤7 days) after the burn, the Berlin criteria for the ARDS diagnosis in this setting may be disputed. Related to this issue, the present study investigated the incidence, trajectory and risk factors of early Acute Respiratory Distress Syndrome (ARDS) and outcome in burn patients, as per the Berlin criteria, along with the concurrent prevalence and influence of inhalation injury, and ventilator-acquired pneumonia (VAP). METHODS: Over a 2.5-year period, burn patients with Total Burn Surface Area (TBSA) exceeding 10% admitted to a national burn center were included. The subgroup of interest comprised patients with more than 48 h of ventilatory support. This group was assessed for ARDS, inhalation injury, and VAP. RESULTS: Out of 292 admissions, 62 sustained burns > 10% TBSA. Of these, 28 (45%) underwent ventilatory support for over 48 h, almost all, 24 out of 28, meeting the criteria for ARDS early, within 7 days post-injury and with a PaO2/FiO2 (PF) ratio nadir at day 5. The mortality rate for this early ARDS group was under 10%, regardless of PF ratios (mean TBSA% 34,8%). Patients with concurrent inhalation injury and early ARDS showed significantly lower PF ratios (p < 0.001), and higher SOFA scores (p = 0.004) but without impact on mortality. Organ failure, indicated by SOFA scores, peaked early (day 3) and declined in the first week, mirroring PF ratio trends (p < 0.001). CONCLUSIONS: The low mortality associated with early ARDS in burn patients in this study challenges the Berlin criteria's for the early ARDS diagnosis, which for its validity relies on that higher mortality is linked to worsening PF ratios. The finding suggests alternative mechanisms, leading to the early ARDS diagnosis, such as the significant impact of inhalation injury on early PF ratios and organ failure, as seen in this study. The concurrence of early organ failure with declining PF ratios, supports, as expected, the hypothesis of trauma-induced inflammation/multi-organ failure mechanisms contributing to early ARDS. The study highlights the complexity in differentiating between the contributions of inhalation injury to early ARDS and the related organ dysfunction early in the burn care trajectory. The Berlin criteria for the ARDS diagnosis may not be fully applicable in the burn care setting, where the low mortality significantly deviates from that described in the original Berlin ARDS criteria publication but is as expected when considering the actual not very extensive burn injury sizes/Baux scores as in the present study.

Alveolar cytokines and interferon autoantibodies in COVID-19 ARDS.

Background: Type I interferon (IFN-I) and IFN autoantibodies play a crucial role in controlling SARS-CoV-2 infection. The levels of these mediators have only rarely been studied in the alveolar compartment in patients with COVID-19 acute respiratory distress syndrome (CARDS) but have not been compared across different ARDS etiologies, and the potential effect of dexamethasone (DXM) on these mediators is not known. Methods: We assessed the integrity of the alveolo-capillary membrane, interleukins, type I, II, and III IFNs, and IFN autoantibodies by studying the epithelial lining fluid (ELF) volumes, alveolar concentration of protein, and ELF-corrected concentrations of cytokines in two patient subgroups and controls. Results: A total of 16 patients with CARDS (four without and 12 with DXM treatment), eight with non-CARDS, and 15 healthy controls were included. The highest ELF volumes and protein levels were observed in CARDS. Systemic and ELF-corrected alveolar concentrations of interleukin (IL)-6 appeared to be particularly low in patients with CARDS receiving DXM, whereas alveolar levels of IL-8 were high regardless of DXM treatment. Alveolar levels of IFNs were similar between CARDS and non-CARDS patients, and IFNα and IFNω autoantibody levels were higher in patients with CARDS and non-CARDS than in healthy controls. Conclusions: Patients with CARDS exhibited greater alveolo-capillary barrier disruption with compartmentalization of IL-8, regardless of DXM treatment, whereas systemic and alveolar levels of IL-6 were lower in the DXM-treated subgroup. IFN-I autoantibodies were higher in the BALF of CARDS patients, independent of DXM, whereas IFN autoantibodies in plasma were similar to those in controls.

Influence of vaccination on critical COVID-19 patients with acute respiratory failure: a retrospective cohort study.

BACKGROUND: Despite vaccines' effectiveness in reducing COVID-19 infection rates and disease severity, their impact on critical patients presenting with acute respiratory failure is elusive. The aim of this study was to further investigate the influence of vaccination on mortality rates among severely ill COVID-19 patients experiencing acute respiratory failure. METHODS: This retrospective cohort study was carried out at a tertiary medical center in Taiwan. From April to September 2022, patients who tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through reverse transcription polymerase chain reaction (RT-PCR) and subsequently experienced acute respiratory failure were included in the study. Baseline characteristics, including vaccination history, along with information regarding critical illness and clinical outcomes, were gathered and compared between patients who received the vaccine and those who did not. RESULTS: A total of 215 patients with COVID-19 exhibiting acute respiratory failure, as confirmed via RT‒PCR, were included in the analysis. Of this cohort, sixty-six (30.7%) patients died within 28 days. Neither administration of the vaccine nor achievement of primary series vaccination status had a significantly different effect on 28 day mortality, number of viral shedding events, acute respiratory distress syndrome (ARDS) incidence or other clinical outcomes. Patients who received the booster vaccine and completed the primary series showed a tendency of increased 28 days of ventilator-free status, though this difference was not statistically significant (p = 0.815). CONCLUSIONS: Vaccination status did not significantly influence mortality rates, the occurrence of ARDS, or the viral shedding duration in COVID-19 patients with acute respiratory failure.

Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

New findings on CD16brightCD62Ldim neutrophil subtypes in sepsis-associated ARDS: an observational clinical study.

Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Results: Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

Intravascular guide wire aspiration in a patient on extracorporeal membrane oxygenation: A case report.

RATIONALE: Guide wire aspiration during central venous catheter (CVC) insertion in a patient on extracorporeal membrane oxygenation (ECMO) is a very rare but dangerous complication. A guide wire aspirated inside the ECMO can cause thrombosis, the ECMO to break down or shut off, and unnecessary ECMO replacement. PATIENT CONCERNS: A 58-year-old man was scheduled for venovenous ECMO for acute respiratory distress syndrome. After his vital signs stabilized, we inserted a CVC. During CVC insertion, the guide wire was aspirated into the ECMO venous line. INTERVENTION: After confirming the guide wire inside the ECMO venous line, we replaced the entire ECMO circuit. OUTCOMES: ECMO was maintained for 57 days, and weaning was successful but the patient died 5 days afterward. LESSONS: Care must be taken when inserting a CVC using a guide wire in ECMO patients: the guide wire should not be inserted deeply, it should be secured during insertion, the ECMO venous cannula tip requires proper positioning, and ECMO flow should be temporarily reduced.

ARDS in solid organ transplant recipients hospitalized for COVID-19 based on the 2023 new definition.

BACKGROUND: Solid organ transplant recipients (SOTRs) are more likely to suffer complications after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVES: We aimed to describe the clinical features of SOTRs infected with SARS-CoV-2 and to assess independent risk factors associated with the development of acute respiratory distress syndrome (ARDS) following COVID-19 infection in SOTRs based on the new ARDS definition. METHODS: 358 SOTRs infected with SARS-CoV-2 were recruited and divided into two groups, patients with ARDS (n = 81) and patients without ARDS (n = 277). Demographic data, initial laboratory findings, therapeutic measures, and outcome indicators were compared between the two groups. The association between the onset of ARDS and related factors was analyzed using a logistic regression model. A nomogram was created to estimate the probability of developing ARDS. RESULTS: Approximately 22.6 % (81/358) of hospitalized SOTRs infected with SARS-CoV-2 developed ARDS. In comparison to patients without ARDS, those with ARDS presented with more underlying conditions, decreased lymphocyte counts and serum albumin levels, but increased levels of leukocytes, serum creatinine, nitrogen urea, uric acid, and inflammatory markers. Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS in this population. Furthermore, a nomogram prediction model was created utilizing the aforementioned factors to facilitate early prediction of ARDS, exhibiting an AUC (area under curve) of 0.81. CONCLUSIONS: Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS following COVID-19 infection in SOTRs.