Extrapulmonary Organ Dysfunction Research Articles

Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus

Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness. This work was funded by the National Natural Science Foundation of China (81761128014).

Multisystem Inflammatory Syndrome in an Adult: A Rare Cause of ST-Segment Elevation MI

The COVID-19 pandemic is a significant worldwide health emergency. Due to the high incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are increasingly recognisable early and long-term outcomes of the disease. One of the uncommon complications of SARS-CoV-2 infection is multisystem inflammatory syndrome in adults (MIS-A). This is a post-sequela of SARS-CoV-2 infection associated with hyperinflammatory syndrome accompanied by extrapulmonary organ dysfunction. The prevalence of MIS-A ranges from 0.2% to 11.7% of the studied SARS-CoV-2 infection cases. The lack of awareness of this condition and unusual constellation of symptoms makes its management challenging. A 36-year-old woman who had a recent SARS-CoV-2 infection presented with chest pain and hypotension. An ECG showed ST-segment elevation in the anteroseptal wall, elevated cardiac enzymes and inflammatory markers. Transthoracic echocardiogram revealed segmental hypokinesia with a mildly reduced ejection fraction of 41%. Coronary angiogram showed normal arteries. A diagnosis of MIS-A was considered and the patient was started on steroids and IV immunoglobulin.

Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

During the second wave of the coronavirus disease 2019 (COVID-19) pandemic, a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction. To describe the clinical and laboratory characteristics, outcomes, and management of these patients, and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders. This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital, between May and August 2021, who fulfilled clearly defined inclusion and exclusion criteria. Outcome was assessed by a change in PaO2/FiO2 ratio and levels of inflammatory markers before and after immunomodulation, duration of mechanical ventilation after starting treatment, and survival to discharge. Five patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction at a median interquartile range (IQR) duration of 32 (23-35) d after the onset of symptoms. These patients had elevated inflammatory markers, required mechanical ventilation for 13 (IQR 10-23) d, and responded to glucocorticoids and/or intravenous immunoglobulin. One patient died (20%). This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome - Adults by the paucity of extrapulmonary organ involvement. The diagnosis can be considered in patients presenting with delayed respiratory worsening, that is not attributable to cardiac dysfunction, fluid overload or ongoing infections, and associated with an increase in systemic inflammatory markers like C-reactive protein, inteleukin-6 and ferritin. A good response to immunomodulation can be expected. This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Systemic cytokines inhibition with Imp7 siRNA nanoparticle ameliorates gut injury in a mouse model of ventilator-induced lung injury

Mechanical ventilation (MV) may negatively affect the lungs and cause the release of inflammatory mediators, resulting in extra-pulmonary organ dysfunction. Studies have revealed systemically elevated levels of proinflammatory cytokines in animal models of ventilator-induced lung injury (VILI); however, whether these cytokines have an effect on gut injury and the mechanisms involved remain unknown. In this study, VILI was generated in mice with high tidal volume mechanical ventilation (20 ml/kg). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 concentrations in serum and gut measured by ELISA showed significant elevation in the VILI mice. Significant increases in gut injury and PANoptosis were observed in the VILI mice, which were positively correlated with the serum levels of TNF-α, IL-1β, and IL-6. The VILI mice displayed intestinal barrier defects, decreased expressions of occludin and zonula occludin-1 (ZO-1), and increased expression of claudin-2 and the activation of myosin light chain (MLC). Importantly, intratracheal administration of Imp7 siRNA nanoparticle effectively inhibited cytokines production and protected mice from VILI-induced gut injury. These data provide evidence of systemic cytokines contributing to gut injury following VILI and highlight the possibility of targeting cytokines inhibition via Imp7 siRNA nanoparticle as a potential therapeutic intervention for alleviating gut injury following VILI.

ICU Mortality Across Prepandemic and Pandemic Cohorts in a Resource-Limited Setting: A Critical Care Resiliency Analysis From South Africa

Hospital adaptation and resiliency, required during public health emergencies to optimize outcomes, are understudied especially in resource-limited settings. What are the prepandemic and pandemic critical illness outcomes in a resource-limited setting and in the context of capacity strain? We performed a retrospective cohort study among patients admitted to ICUs at two public hospitals in the KwaZulu-Natal Department of Health in South Africa preceding and during the COVID-19 pandemic (2017-2022). We used multivariate logistic regression to analyze the association between three patient cohorts (prepandemic non-COVID-19, pandemic non-COVID-19, and pandemic COVID-19) and ICU capacity strain and the primary outcome of ICU mortality. Three thousand two hundred twenty-one patients were admitted to the ICU during the prepandemic period and 2,539 patients were admitted to the ICU during the pandemic period (n = 375 [14.8%] with COVID-19 and n = 2,164 [85.2%] without COVID-19). The prepandemic and pandemic non-COVID-19 cohorts were similar. Compared with the non-COVID-19 cohorts, the pandemic COVID-19 cohort showed older age, higher rates of chronic cardiovascular disease and diabetes, less extrapulmonary organ dysfunction, and longer ICU length of stay. Compared with the prepandemic non-COVID-19 cohort, the pandemic non-COVID-19 cohort showed similar odds of ICU mortality (OR, 1.06; 95% CI, 0.90-1.25; P = .50) whereas the pandemic COVID-19 cohort showed significantly increased odds of ICU mortality (OR, 3.91; 95% CI, 3.03-5.05 P < .0005). ICU occupancy was not associated with ICU mortality in either the COVID-19 cohort (OR, 1.05 per 10% change in ICU occupancy; 95% CI, 0.96-1.14; P = .27) or the pooled non-COVID-19 cohort (OR, 1.01 per 10% change in ICU occupancy; 95% CI, 0.98-1.03; P = .52). Patients admitted to the ICU before and during the pandemic without COVID-19 were broadly similar in clinical characteristics and outcomes, suggesting critical care resiliency, whereas patients admitted to the ICU with COVID-19 showed important clinical differences and significantly higher mortality.

Case of multisystem inflammatory syndrome in adults

Introduction and aim. Multisystem inflammatory syndrome in adults (MIS-A) is a rare severe illness which is related to prior SARS-CoV2 infection in individuals&gt;=21 years old. The condition was described few months after recognition of similar entity in children known as MIS-C (United Kingdom, April, 2020). The diagnosis of MIS-A is based on clinical symptoms andevidence of inflammation in laboratory markers. It is characterized by extrapulmonary organ dysfunction (cardiovascular, gastrointestinal), general symptoms such as fever, malaise, rash and deviations in blood tests (elevated level of ferritin, procalcitonin, CRP, IL-6, D-Dimer) with a previous or current SARS-CoV-2 infection. The purpose of this study is to present the syndrome on the basis of a clinical case example, to show the course of the disease, its symptoms and the result of applied treatment. Description of the case. The following case describes the clinical history, diagnostic process and applied treatment of 37-year old female patient who was admitted urgently to the hospital with a suspicion of sepsis originating from pharynx. The final diagnosis – MIS-A was settled after performing a broad panel of tests. Clinical picture was non- characteristic. The patient was successfully treated with steroids. Conclusion. MIS-A is a rare clinical entity linked with SARS-CoV-2 infection. The symptoms manifest from multiple organ systems and the diagnostic process may be challenging. The illness can be successfully treated with steroids.

P50 implies adverse clinical outcomes in pediatric acute respiratory distress syndrome by reflecting extrapulmonary organ dysfunction

Hypoxemia and multiple organ dysfunction are significant contributors to mortality in patients with pediatric acute respiratory distress syndrome (PARDS). P50, the oxygen tension at which hemoglobin is 50% saturated, is a measure of hemoglobin-oxygen affinity, and its alteration might have implications for tissue hypoxia and organ dysfunction. The purpose of this single-center, retrospective study was to evaluate P50 levels in PARDS and to determine the association between P50 and clinical outcomes. The study included 212 children diagnosed with PARDS according to the Pediatric Acute Lung Injury Consensus Conference definition who required invasive mechanical ventilation and had arterial blood gas results of hemoglobin oxygen saturation < 97% at the time of diagnosis. P50 levels were calculated using Doyle’s method, and organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 score. Most patients exhibited more than one dysfunctional extrapulmonary organ at PARDS onset. P50 increased with increasing PARDS severity (mild (26.6 [24.9–29.6]), moderate (26.8 [25.0–29.5]), and severe PARDS (29.1 [26.1–32.4] mmHg; P = 0.025). Moreover, P50 demonstrated a significant positive association with extrapulmonary organ dysfunction score (β = 0.158, P = 0.007) and risk of mortality (adjusted hazard ratio, 1.056; 95% confidence interval, 1.015–1.098; P = 0.007), irrespective of initial PARDS severity. The relationship between P50 and mortality was largely mediated by extrapulmonary organ dysfunction. A high P50 value at the time of PARDS diagnosis may be associated with mortality via dysfunctional extrapulmonary organs. Future studies should consider P50 as a potential candidate index for risk stratification of PARDS patients.

Identification of cardiovascular and molecular prognostic factors for the morbidity and mortality in COVID-19-sepsis (ICROVID): Protocol for a prospective multi-centre cohort study.

IntroductionSevere COVID-19 constitutes a form of viral sepsis. Part of the specific pathophysiological pattern of this condition is the occurrence of cardiovascular events. These include pulmonary embolism, arrhythmias and cardiomyopathy as manifestations of extra-pulmonary organ dysfunction. Hitherto, the prognostic impact of these cardiovascular events and their predisposing risk factors remains unclear. This study aims to explore this question in two cohorts of viral sepsis–COVID-19 and influenza–in order to identify new theragnostic strategies to improve the short- and long-term outcome of these two diseases.Methods and analysisIn this prospective multi-centre cohort study, clinical assessment will take place during the acute and post-acute phase of sepsis and be complemented by molecular laboratory analyses. Specifically, echocardiography and cardiovascular risk factor documentation will be performed during the first two weeks after sepsis onset. Aside from routine haematological and biochemical laboratory tests, molecular phenotyping will comprise analyses of the metabolome, lipidome and immune status. The primary endpoint of this study is the difference in 3-month mortality of patients with and without septic cardiomyopathy in COVID-19 sepsis. Patients will be followed up until 6 months after onset of sepsis via telephone interviews and questionnaires. The results will be compared with a cohort of patients with influenza sepsis as well as previous cohorts of patients with bacterial sepsis and healthy controls.Ethics and disseminationApproval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (2020-2052-BO). The results will be published in peer-reviewed journals and presented at appropriate conferences.Trial registrationDRKS00024162.

Abstract 11986: A Safety Study of Intermittent versus Continuous Inhaled NO Therapy in Spontaneously Breathing COVID-19 Patients: A Randomized Controlled Trial

Introduction: Nitric oxide (NO) inhalation (iNO) therapy has been approved as a salvage therapy in patients with acute respiratory distress syndrome. However, the optimal patterns of therapeutic administration and iNO efficacy in COVID-19 patients with hypoxemia have not been studied so far. Hypothesis: A combination of high-concentration intermittent iNO treatment with continuous low-concentration NO gas supplementation between therapeutic high-dose iNO sessions may be a safe approach in COVID-19 patients with hypoxemia compared with the high-dose spike therapy alone. Methods: A single-center randomized controlled trial examined the safety of administration of intermittent high-dose iNO therapy versus the intermittent therapy in the presence of continuous low-dose iNO in spontaneously breathing COVID-19 patients (www.clinicaltrials.gov #NCT04476992). The study comprised adult patients tested positive for the COVID-19 by RT-PCR, who required oxygen and was admitted to the respiratory hospital. After attrition, a total of 20 patients were enrolled and randomized to the group of intermittent high-dose iNO treatment combined with continuous low-dose NO supplementation (group 1) or the group of intermittent high-dose iNO treatment(group 2). Control group (group 3) comprised retrospective patients who received conventional treatment for COVID-19 in hospital. Results: Administration of intermittent high-dose iNO therapy combined with continuous low-dose NO supplementation significantly improved physiological interactions in the heart-lung blood circulation system and was not associated with the extrapulmonary organ dysfunction. Safety parameters are presented in Table 1. Conclusions: High-dose intermittent iNO therapy combined with continuous low-dose NO gas supplementation may be considered a safe adjuvant modality of treatment for COVID-19 in spontaneously breathing hypoxemic patients.

Beyond the Alveolar Epithelium: Plasma Soluble Receptor for Advanced Glycation End Products Is Associated With Oxygenation Impairment, Mortality, and Extrapulmonary Organ Failure in Children With Acute Respiratory Distress Syndrome.

Soluble receptor for advanced glycation end products is a known plasma marker of alveolar epithelial injury. However, RAGE is also expressed on cell types beyond the lung, and its activation leads to up-regulation of pro-inflammatory mediators. We sought to examine the relationship between plasma soluble receptor for advanced glycation end products and primary pulmonary dysfunction, extrapulmonary organ dysfunction, and mortality in pediatric acute respiratory distress syndrome patients at two early time points following acute respiratory distress syndrome diagnosis and compare these results to plasma surfactant protein-D, a marker of pure alveolar epithelial injury. Prospective observational study. Five academic PICUs. Two hundred fifty-eight pediatric patients 30 days to 18 years old meeting Berlin Criteria for acute respiratory distress syndrome. None. Plasma was collected for soluble receptor for advanced glycation end products and surfactant protein-D measurements within 24 hours (day 1) and 48 to 72 hours (day 3) after acute respiratory distress syndrome diagnosis. Similar to surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with a higher oxygenation index (p < 0.01) and worse lung injury score (p < 0.001) at the time of acute respiratory distress syndrome diagnosis. However, unlike surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with worse extrapulmonary Pediatric Logistic Organ Dysfunction score during ICU stay (day 3; p < 0.01) and positively correlated with plasma levels of interleukin-6 (p < 0.01), tumor necrosis factor-α (p < 0.01), and angiopoietin-2 (p < 0.01). Among children with indirect lung injury, plasma soluble receptor for advanced glycation end products was associated with mortality independent of age, sex, race, cancer/bone marrow transplant, and Pediatric Risk of Mortality score (day 3; odds ratio, 3.14; 95% CI, 1.46-6.75; p < 0.01). Unlike surfactant protein-D, which is primarily localized to the alveolar epithelium plasma soluble receptor for advanced glycation end products is systemically expressed and correlates with markers of inflammation, extrapulmonary multiple organ dysfunction, and death in pediatric acute respiratory distress syndrome with indirect lung injury. This suggests that unlike surfactant protein-D, soluble receptor for advanced glycation end products is a multifaceted marker of alveolar injury and increased inflammation and that receptor for advanced glycation end products activation may contribute to the pathogenesis of multiple organ failure among children with indirect acute respiratory distress syndrome.

A CASE OF MULTISYSTEM INFLAMMATORY SYNDROME IN AN ADULT PATIENT PRESENTING AS SEPTIC SHOCK

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Multisystem Inflammatory Syndrome-Adults (MIS-A) has been recognized as a severe illness requiring hospitalization in a person aged 21 or older, with laboratory evidence of current or previous SARS-CoV-2 infection, severe extra-pulmonary organ dysfunction, laboratory evidence of severe inflammation and minimal of respiratory disease (1). It was initially recognized in children as Kawasaki disease-like illness after COVID-19. There have been several cases reported in children, however, only a few reported in adults. CASE PRESENTATION: We present the case of a 49-year old woman with chief complaints of generalized weakness, sore throat, and lower abdominal pain. Her medical history was significant for COVID-19 infection 2 months prior. On presentation she was hemodynamically unstable with heart rate of 134/min, blood pressure of 86/36 mm Hg, respiratory rate of 32/min, oxygen saturation of 92% on room air and temperature of 102.8 F. Physical examination was positive for dry mucous membranes, pharyngeal erythema, cervical lymphadenopathy and lower abdominal tenderness. Initial investigations were consistent with DIC and septic shock. She was treated with multiple vasopressors. She was placed on intravenous broad-spectrum antibiotics. Her SARS-CoV-2 PCR was negative, but SARS-CoV-2 IgG and IgM antibodies came back positive. Her chest x-ray was unremarkable. She also had elevated inflammatory markers including C-reactive protein, lactate dehydrogenase and ferritin. Due to her history of Covid-19 infection, positive antibodies to SARS-CoV-2, high grade fever, elevated inflammatory markers and multi-organ dysfunction a diagnosis of multisystem inflammatory syndrome was made. Her case was reported and discussed with CDC team as well. Patient was started on intravenous high-dose corticosteroids. After starting therapy, significant improvement was seen in patient's clinical status. Her corticosteroids were tapered off and patient was eventually discharged home in stable condition. DISCUSSION: This case highlights that adult patients with SARS-CoV-2 infection can develop a hyperinflammatory syndrome even as late as 60 days. Previously the onset of MIS-A has been reported 2-5 weeks after initial diagnosis (1). These patients can have minimal respiratory symptoms. The pathophysiology of MIS-A is unclear. High clinical suspicion in conjunction with antibody, viral testing, and inflammatory markers will assist in the diagnosis. Treatment used for MIS-A includes supportive care, steroids, anticoagulation, antivirals, and/or IL-6 inhibitors. CONCLUSIONS: This case emphasizes the importance of early recognition and prompt treatment of multisystem inflammatory syndrome in adults to prevent significant morbidity and mortality. Considering rarity and novelty of this disease, physicians should have high clinical suspicion in adults with history of COVID-19 infection. REFERENCE #1: CDC. Information for healthcare providers about multisystem inflammatory syndrome in adults (MIS-A). Atlanta, GA: US Department of Health and Human Services, CDC;2020. https://www.cdc.gov/mis-c/hcp/ DISCLOSURES: No relevant relationships by Manaquibb Zain Khan, source=Web Response No relevant relationships by SOHAIB KHAN, source=Web Response No relevant relationships by faisal mahfooz, source=Web Response No relevant relationships by Mehul Patel, source=Web Response

Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction

BackgroundTo date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD.MethodsThe clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD.ResultsThe ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time.ConclusionsThe cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.

Characteristics and Outcome of Severe Mycoplasma pneumoniae Pneumonia Admitted to PICU in Shanghai: A Retrospective Cohort Study.

Objectives:We aimed to describe the characteristics and outcome in children with severe Mycoplasma pneumoniae pneumonia in a Chinese PICU.Design:A retrospective observational study from 2017 to 2019.Setting:A 36-bed university tertiary PICU at Shanghai Children’s Hospital.Patients:Patients admitted to a tertiary PICU 29 days to 18 years old screened for laboratory-confirmed severe M. pneumoniae pneumonia.Interventions:None.Measurements and Main Results:Descriptive analysis of baseline characteristics for patients included hospital mortality, organ dysfunctions, use of mechanical ventilation, continuous renal replacement therapy, and/or extracorporeal membrane oxygenation. A total of 817 children with severe pneumonia were admitted to PICU, and 203 of 817 cases (24.8%) with severe M. pneumoniae pneumonia were included in this study. The median age was 41 months (interquartile range, 20–67 mo), of which 77.3% (157/203) were younger than 6 years old. Among 163 patients with the test for macrolide resistance, 90.2% cases (147/163) were macrolide-resistant M. pneumoniae. Severe M. pneumoniae pneumonia-associated organ dysfunction included acute respiratory failure (203 cases, 100%), followed by cardiovascular disorder (79/203, 38.9%), gastrointestinal dysfunction (24/203, 11.8%). The main complications were pleural effusion (79/203, 38.9%), capillary leak syndrome (58/203, 28.6%), and plastic bronchitis (20/203, 9.9%). All patients needed respiratory support, including 64.5% patients (131/203) who received mechanical ventilation and 35.5% patients (72/203) who received high-flow nasal oxygen. Twenty-five patients (12.3%) treated with continuous renal replacement therapy and nine cases (4.4%) received extracorporeal membrane oxygenation. The case fatality rate was 3.9% (8/203). Furthermore, cardiovascular dysfunction, liver injury, or multiple organ dysfunction syndrome were associated with longer mechanical ventilation duration, delayed PICU discharge, and high hospital mortality. Coinfection was a risk factor of delayed PICU discharge.Conclusions:Children with severe M. pneumoniae pneumonia mainly occur under the age of 6 years, showing a high proportion of extrapulmonary organ dysfunction and macrolide resistances. Extrapulmonary organ dysfunction and coinfection are associated with worse outcomes. The overall mortality is relatively low after treated with appreciate antibiotics, respiratory support, and extracorporeal life support.

Assessment of clinical features and renal functions in Coronavirus disease-19: A retrospective analysis of 96 patients.

The most common extra pulmonary organ dysfunction in acute respiratory distress syndrome is acute kidney injury. Current data so far indicate low incidence of AKI in Covid-19 disease. In this retrospective study, we analysed the clinical features of patients diagnosed with Covid-19 and investigated the effect of Covid-19 on kidney function. Ninety-six patients diagnosed with Covid-19 were included in our study. Demographic features (Age, gender, co-morbidities), symptoms, thorax CT findings, Covid-19 PCR results and laboratory findings were recorded. The clinical features of the patients were analysed and kidney function values before Covid-19 diagnosis were compared with kidney function values after Covid-19 diagnosis. Most presenting symptom was fever (51%). Most accompanying co-morbidity was hypertension (56%). According to laboratory findings; ferritin, D-dimer and C-reactive protein levels were statistically significantly higher in ARDS group than severe pneumonia and pneumonia group (P=.002, P=.001 and P<.001, respectively). Also lymphocyte levels were statistically significantly lower in ARDS group than severe pneumonia and pneumonia group (P=.042). According to KDIGO criteria 3 (3.1%) patients had AKI during the hospital stay. For all patients, there was statistically significant difference between basal, 1st, 5th and 10th day BUN and SCr levels (P=.024 and P=.018, respectively). For severe pneumonia group there was statistically significant difference between basal, 1st, 5th and 10th day SCr levels (P=.045). Our study demonstrated that Covid-19 can cause renal impairment both with pneumonia and ARDS. A large-scale prospective randomised studies are needed to reach final judgement about this topic.

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

BackgroundOver 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed.MethodsThis prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation.FindingsBetween March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51–72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 [63%]) and diabetes (92 [36%]). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9–28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1–6). In the multivariable Cox model, older age (adjusted hazard ratio [aHR] 1·31 [1·09–1·57] per 10-year increase), chronic cardiac disease (aHR 1·76 [1·08–2·86]), chronic pulmonary disease (aHR 2·94 [1·48–5·84]), higher concentrations of interleukin-6 (aHR 1·11 [95%CI 1·02–1·20] per decile increase), and higher concentrations of D-dimer (aHR 1·10 [1·01–1·19] per decile increase) were independently associated with in-hospital mortality.InterpretationCritical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality.FundingNational Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.

Doxycycline for the empiric treatment of low-severity hospital acquired pneumonia

Background In the U.K., doxycycline is widely recommended as first-line empiric treatment for mild HAP, however this practice is based on expert opinion and we are aware of no data describing the outcomes of patients treated with doxycycline. Here we describe the outcomes of non-ICU patients treated empirically with doxycycline for low-severity HAP. Methods 1680 inpatient chest x-rays were manually screened to identify cases of HAP. HAP was defined as new or progressive CXR consolidation occurring ³48 hours after admission, combined with compatible symptoms or signs. Treatment failure was defined as requirement for antimicrobial escalation, HAP recurrence or mortality attributed to HAP. We compared groups according to treatment outcome using the Kruskal-Wallis test and receiver operator characteristic (ROC) analysis. Results Forty-nine patients who received doxycycline were included in the analysis. The median age was 78 years and 63% had &gt;2 co-morbidities. Hypoxia was common (57%) but extra-pulmonary organ dysfunction was uncommon. 71% of patients were successfully treated with doxycycline as first-line empiric therapy. Treatment failure was associated with increased duration of hospitalisation prior to HAP onset (median 21.5 vs. 10 days, p=0.03) and higher neutrophil count (10.1 vs. 6.1 x109L-1, p=0.04). ROC analysis identified HAP onset &gt;14 days after admission as the optimum cut-off for predicting treatment failure. Conclusions In this cohort, the majority of patients with low-severity HAP were successfully treated with doxycycline. Treatment failure was associated with prolonged hospitalisation prior to HAP onset with 14d identified as a potential surrogate marker for patients requiring antimicrobials against Gram-negative organisms.

Time-Course of Physiologic Variables During Extracorporeal Membrane Oxygenation and Outcome of Severe Acute Respiratory Distress Syndrome.

In patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS), it is unknown which clinical physiologic variables should be monitored to follow the evolution of lung injury and extrapulmonary organ dysfunction and to differentiate patients according to their course. We analyzed the time-course of prospectively collected clinical physiologic variables in 83 consecutive ARDS patients undergoing ECMO at a single referral center. Selected variables-including ventilator settings, respiratory system compliance, intrapulmonary shunt, arterial blood gases, central hemodynamics, and sequential organ failure assessment (SOFA) score-were compared according to outcome at time-points corresponding to 0%, 25%, 50%, 75%, and 100% of the entire ECMO duration and daily during the first 7 days. A logistic regression analysis was performed to identify changes between ECMO start and end that independently predicted hospital mortality. Tidal volume, intrapulmonary shunt, arterial lactate, and SOFA score differentiated survivors and nonsurvivors early during the first 7 days and over the entire ECMO duration. Respiratory system compliance, PaO2/FiO2 ratio, arterial pH, and mean pulmonary arterial pressure showed distinct temporal course according to outcome over the entire ECMO duration. Lack of improvement of SOFA score independently predicted hospital mortality. In ARDS patients on ECMO, temporal trends of specific physiologic parameters differentiate survivors from non-survivors and could be used to monitor the evolution of lung injury. Progressive worsening of extrapulmonary organ dysfunction is associated with worse outcome.

Telomeres in Interstitial Lung Disease: The Short and the Long of It.

Telomeres are repetitive nucleotide sequences that cap linear chromosomes, thereby limiting progressive chromosomal shortening during cell replication. In conjunction with environmental factors, common single-nucleotide polymorphisms and rare and ultra-rare telomere-related mutations are associated with accelerated telomere shortening resulting in organ dysfunction, including interstitial lung disease (ILD). The most common telomere-related mutation-associated ILD is idiopathic pulmonary fibrosis (IPF). Up to one-third of individuals with familial IPF have shortened telomeres and/or carry a telomere-related mutation, and 1 in 10 individuals with sporadic IPF have telomere-related mutations. Regardless of ILD phenotype, individuals with short telomeres and/or known telomere-related mutations have more rapid disease progression and shorter lung transplant-free survival. Management should include initiation of antifibrotic agents for those with an IPF phenotype and early referral to a transplant center. Patients with ILD being considered for transplant should be screened for short telomeres if there is a significant family history of pulmonary fibrosis or evidence of extrapulmonary organ dysfunction associated with a short telomere syndrome. Post-transplant management of recipients with telomere-related mutations should include careful adjustment of immunosuppression regimens on the basis of bone marrow reserve. Data on the impact of shortened telomeres on post-transplant outcomes, however, remain mixed.

Characteristics and prognostic factors of previously healthy children who required respiratory support in a pediatric intensive care unit

Purpose: Comorbidities have been considered a mortality risk factor in pediatric critical care patients. We studied the characteristics and prognostic factors of children without comorbidities who were admitted to the intensive care unit (ICU) due to respiratory failure. Methods: We reviewed the medical charts of patients (<18 years) admitted to the ICU for respiratory support in a single tertiary cen ter between January 2006 and December 2016. Patients with comorbidities and perioperative statuses were excluded. Results: Of the 4,712 ICU patients, 73 (1.5%) were included in this study. The median age was 31 months (8-57) and 51 (69.9%) were boys. Twenty-nine patients (39.7%) presented with pneumonia, 14 (19.2%) with acute respiratory distress syndrome (ARDS), and 11 (15.1%) with obstructive airway disease. The median duration of ICU hospitalization was 5 days (2-14.5), and 45 of the 73 patients (61.6%) needed mechanical ventilation. Mortality was 13.7% (10/73). None of the patients with pneumonia or obstructive airway disease died. The most frequent cause of death was ARDS (5 of 10, 50%). In adjusted analysis, the extent of extrapulmonary organ dysfunction was significantly associated with mortality (odds ratio, 2.89; 95% confidence interval, 1.17-7.11; P=0.023). Conclusion: The mortality rate of previously healthy pediatric patients needing respiratory support in the ICU should not be negligi ble. Multiple organ dysfunctions might be a significant risk factor for mortality in such patients. (Allergy Asthma Respir Dis 2018;6:103-109)

Multiple Organ Dysfunction in Children Mechanically Ventilated for Acute Respiratory Failure.

The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure. Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013. Thirty-one academic PICUs in the United States. Two thousand four hundred forty-nine children mechanically ventilated for acute respiratory failure enrolled in Randomized Evaluation of Sedation Titration for Respiratory Failure. Organ dysfunction was defined using criteria published for pediatric sepsis. Multiple organ dysfunction syndrome was defined as respiratory dysfunction one or more extrapulmonary organ dysfunctions. We used multivariable logistic regression to identify risk factors for multiple organ dysfunction syndrome, and logistic or proportional hazards regression to compare clinical outcomes. All analyses accounted for PICU as a cluster variable. Overall, 73% exhibited extrapulmonary organ dysfunction, including 1,547 (63%) with concurrent multiple organ dysfunction syndrome defined by onset on day 0/1 and 244 (10%) with new multiple organ dysfunction syndrome with onset on day 2 or later. Most patients (93%) with indirect lung injury from sepsis presented with concurrent multiple organ dysfunction syndrome, whereas patients with direct lung injury had both concurrent (56%) and new (12%) multiple organ dysfunction syndrome. Risk factors for concurrent multiple organ dysfunction syndrome included older age, illness severity, sepsis, cancer, and moderate/severe lung injury. Risk factors for new multiple organ dysfunction syndrome were moderate/severe lung injury and neuromuscular blockade. Both concurrent and new multiple organ dysfunction syndrome were associated with 90-day in-hospital mortality (concurrent: adjusted odds ratio, 6.54; 95% CI, 3.00-14.25 and new: adjusted odds ratio, 3.21; 95% CI, 1.48-6.93) after adjusting for sepsis, moderate/severe lung injury, and other baseline characteristics. Extrapulmonary organ dysfunction was common, generally occurred concurrent with respiratory dysfunction (especially in sepsis), and was a major risk factor for mortality in pediatric acute respiratory failure.