Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta-analysis.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID-19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID-19 pneumonia. However, data regarding the role of PDS in COVID-19 is still unclear. Therefore, we performed this meta-analysis to evaluate the role of PDS in COVID-19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID-19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92-1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37-1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: -1.46-5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56-1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.

RNAseq analysis of bronchial epithelial cells to identify COPD-associated genes and SNPs.

BACKGROUND: There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis. We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD. METHODS: To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.7, FEV1% < 80%), and 30 non-COPD controls. Targeted next generation sequencing was used to measure total and allele-specific expression of 35 genes in genome maintenance (GM) genes pathways linked to COPD pathogenesis, including seven TP53 and CEBP transcription factor family members. Shrinkage linear discriminant analysis (SLDA) was used to identify COPD-classification models. COPD GWAS were queried for putative cis-regulatory SNPs in the targeted genes. RESULTS: On a network basis, TP53 and CEBP transcription factor pathway gene pair network connections, including key DNA repair gene ERCC5, were significantly different in COPD subjects (e.g., Wilcoxon rank sum test for closeness, p-value = 5.0E-11). ERCC5 SNP rs4150275 association with chronic bronchitis was identified in a set of Lung Health Study (LHS) COPD GWAS SNPs restricted to those in putative regulatory regions within the targeted genes, and this association was validated in the COPDgene non-hispanic white (NHW) GWAS. ERCC5 SNP rs4150275 is linked (D' = 1) to ERCC5 SNP rs17655 which displayed differential allelic expression (DAE) in BEC and is an expression quantitative trait locus (eQTL) in lung tissue (p = 3.2E-7). SNPs in linkage (D' = 1) with rs17655 were predicted to alter miRNA binding (rs873601). A classifier model that comprised gene features CAT, CEBPG, GPX1, KEAP1, TP73, and XPA had pooled 10-fold cross-validation receiver operator characteristic area under the curve of 75.4% (95% CI: 66.3%-89.3%). The prevalence of DAE was higher than expected (p = 0.0023) in the classifier genes. CONCLUSIONS: GM genes comprised by COPD-associated BEC expression patterns were enriched for SNPs with cis-regulatory function, including a putative cis-rSNP in ERCC5 that was associated with COPD risk. These findings support additional total and allele-specific expression analysis of gene pathways with high prior likelihood for involvement in COPD pathogenesis.

Hypertriglyceridemia-Induced Pancreatitis in Psychiatric Patients: A Case Report and Review of Literature.

Hypertriglyceridemia is a known cause of 2%-7% of cases of acute pancreatitis. Although there are numerous potential causes, the use of atypical antipsychotics has been linked to elevated triglycerides and pancreatitis. Here, we present the case of a 42-year-old male patient with a diagnosis of schizoaffective disorder who presented to our hospital with acute pancreatitis due to hypertriglyceridemia, which was exacerbated after he was started on quetiapine.

Fecal Transplant for Treatment of Toxic Megacolon Associated With Clostridium Difficile Colitis in a Patient With Duchenne Muscular Dystrophy.

Clostridium difficile (C diff) colitis infection is the most common cause of nosocomial infectious diarrhea and the prevalence is increasing worldwide. Toxic megacolon is a severe complication of C diff colitis associated with high mortality. Gastrointestinal (GI) comorbidity and impaired smooth muscle contraction are risk factors for the development of C diff-associated toxic megacolon. We present a case of fulminant C diff colitis with toxic megacolon in a patient with Duchenne muscular dystrophy (DMD) in the intensive care unit. C diff colitis was diagnosed by clinical presentation and positive C diff DNA amplification test (polymerase chain reaction). The impairment of GI tract due to DMD predisposes these patients to severe C diff infection and toxic megacolon, as observed in this case report. For the same reason, the recovery of GI function in these patients can be prolonged. While surgery was conducted for relieving the pressure from toxic megacolon, fecal microbiota transplantation through colonoscopy resulted in successful resolution of the C diff symptoms, although the recovery is prolonged due to DMD.

Management of familial hypertriglyceridemia-induced pancreatitis during pregnancy with therapeutic plasma exchange: a case report and review of literature.

Familial severe hypertriglyceridemia (levels greater than 1000 mg/dL) is a known cause of acute pancreatitis. Pregnancy can dysregulate controlled lipid levels in women with familial hypertriglyceridemia and lead to acute pancreatitis and significant morbidity in both mother and fetus. We report a case of hypertriglyceridemia-induced pancreatitis during pregnancy that was successfully treated using therapeutic plasma exchange, resulting in delivery of a healthy preterm infant. Therapeutic plasma exchange is an effective approach to treat gestational hypertriglyceridemia-induced pancreatitis. Other treatment options include combined heparin and insulin infusion. Moreover, particular caution should be applied when interpreting the results of prothrombin time in the setting of severe hypertriglyceridemia as false elevation with testing methods could happen.

Complement-Mediated Thrombotic Microangiopathy and Spontaneous Splenic Rupture Associated With Cytomegalovirus Infection.

This is a case report of a previously healthy female patient with complement-mediated thrombotic microangiopathy (TMA) caused by a systemic cytomegalovirus infection that was successfully treated with plasmapheresis, steroids, and parenteral valganciclovir. Complement-mediated TMA is the result of various genetic mutations leading to complement abnormalities with overactivation of alternate complement pathway in response to a triggering infection. She also had splenic rupture without splenomegaly and was managed successfully without splenectomy.

Demographics and Outcomes of Extracorporeal Membrane Oxygenation in COVID-19 Patients: National Database Analysis.

INTRODUCTION: The effectiveness of extracorporeal membrane oxygenation (ECMO) in treating COVID-19 patients has been variable. To gain a better insight, we examined the outcomes of ECMO in COVID-19 patients using data from the 2020 National Inpatient Sample database. METHODS: We analyzed data from adult hospital admissions where COVID-19 was the primary diagnosis. The primary outcome was all-cause inpatient mortality. Secondary outcomes were length of stay (LOS), cost, and discharge disposition. RESULTS: We identified 1,048,025 COVID-19 admissions, of which 98,528 were on mechanical ventilation (MV), and only 1.8% received ECMO. In-hospital mortality of mechanically ventilated patients who received ECMO was 49%, compared to 59% with no ECMO (p < 0.001). ECMO treatment was associated with a reduced risk of mortality (HR = 0.67, p < 0.0001, CI 0.57-0.79) even after adjustment for confounders and other comorbidities. Patients on ECMO had significantly extended hospital stays and were more likely to be discharged to an acute care facility. Younger and male patients were more likely to receive ECMO treatment. Females had a lower mortality risk, while race and obesity were not associated with an increased risk of death. CONCLUSION: ECMO treatment may offer survival benefits in severe COVID-19. Based on our findings, we suggest early ECMO treatment for patients with a high mortality risk.

Micafungin-induced thrombotic thrombocytopenic purpura: a case report and review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction leading to organ dysfunction. Drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome has been recognized for several years. The most commonly implicated drugs are mitomycin C, cyclosporine, quinine, clopidogrel, and ticlopidine. Recent advances have suggested that like in idiopathic TTP, the most likely pathogenesis for drug-induced TTP is either an immune-mediated phenomenon involving the ADAMTS13 metalloprotease or direct endothelial toxicity. In this communication, we report a case of micafungin-induced TTP. Micafungin is a new antifungal drug of the Echinocandins group. Whether micafungin induces autoantibodies against ADAMTS13 or not, this needs further evaluation, but TTP should be recognized as a possible complication of micafungin. Clinicians should be alert to this adverse effect of micafungin and monitor platelet counts in patients receiving this drug.

Does a Starting Positive End-Expiratory Pressure of 8 cmH2O Decrease the Probability of a Ventilator-Associated Event?

Introduction: Ventilator-associated events (VAEs) are objective measures as defined by the Centers for Disease Control and Prevention (CDC). To reduce VAEs, some hospitals have started patients on higher baseline positive end-expiratory pressure (PEEP) to avoid triggering VAE criteria due to respiratory fluctuations. Methods: At our institution, VAEs were gathered from January 2014 through December 2019. Using the CDC-defined classifications, VAEs were split into two groups to separate patients with hypoxemia only (VAC) and those with hypoxemia and evidence of inflammation or infection (IVAC-plus). We used the geometric distribution to calculate the daily event probability before and after the protocol implementation. A probability threshold was used to determine if the days between events was exceeded during the post-protocol period. Results: A total of 306 VAEs were collected over the study period. Of those, 155 were VACs and 107 were IVAC-plus events during the pre-protocol period. After implementing the protocol, 24 VACs and 20 IVAC-plus events were reported. There was a non-significant decrease in daily event probabilities in both the VAC and IVAC-plus groups (0.083 vs. 0.068 and 0.057 vs. 0.039, respectively). Conclusion: We concluded a starting PEEP of 8 cmH2O is unlikely to be an effective intervention at reducing the probability of a VAE. Until specific guidelines by the CDC are established, hospitals should consider alternative methods to reduce VAEs.

Neurological Predictors of Clinical Outcomes in Hospitalized Patients With COVID-19.

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection. Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10-12) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death. Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

Case-control study investigating parameters affecting ventilator-associated events in mechanically ventilated patients.

We analyzed a set of clinical parameters using Cox proportional hazard regressions to yield significant factors associated with the development of ventilator-associated events. In our study, intubation site, certain comorbidities, morphine, prednisone, and nutrition emerged as factors. Additionally, we presented potential mechanisms that require further research to validate.

Hemophagocytic Lymphohistiocytosis in the Elderly.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of massive, dysregulated cytokine release and secondary multiorgan failure and is associated with high mortality. Primary HLH occurs predominately in infants and young children with a genetic predisposition. Acquired HLH is less well characterized and usually occurs in younger adults in the setting of severe inflammation triggered by infection or malignancy. Little is known about the disease in elderly. We report 3 patients >50 years old who presented with multiorgan failure and shock without an identifiable source and were ultimately diagnosed with acquired HLH. We performed a literature review of HLH in adults >50 years of age and identified an additional 68 cases. Mean age was 62 years, with male predominance. Most cases were triggered by infection (49%) followed by malignancy (27%). Nineteen patients were treated with the HLH-94 protocol, 11 received corticosteroids and the remainder received non-HLH specific interventions. Overall mortality was 62%.

Assessment of ventilator-associated events using the geometric distribution.

Hospital-acquired rare events, such as nosocomial infections and other low-occurring incidents, in the clinical environment are difficult to monitor using traditional quality indicators. Using the Centers for Disease Control and Prevention definition of ventilator-associated events, we demonstrate an alternative method for assessment of rare events.

Posterior Reversible Encephalopathy Syndrome Secondary to CSF Leak and Intracranial Hypotension: A Case Report and Literature Review.

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical neuroradiological condition characterized by insidious onset of neurological symptoms associated with radiological findings indicating posterior leukoencephalopathy. PRES secondary to cerebrospinal fluid (CSF) leak leading to intracranial hypotension is not well recognized etiology of this condition. Herein, we report a case of PRES that occurred in the setting of CSF leak due to inadvertent dural puncture. Patient underwent suturing of the dural defect. Subsequently, his symptoms resolved and a repeated brain MRI showed resolution of brain lesions. The pathophysiology and mechanistic model for developing PRES in the setting of intracranial hypotension were discussed. We further highlighted the importance of tight blood pressure control in patients with CSF leak and suspected intracranial hypotension because they are more vulnerable to develop PRES with normal or slightly elevated bleed pressure values.

Kaposiform lymphangiomatosis, a newly characterized vascular anomaly presenting with hemoptysis in an adult woman.

Disorders of the pulmonary lymphatic system include macro- and microcystic lymphatic malformations, primary or secondary lymphangiectasias, generalized lymphatic anomalies, diffuse pulmonary lymphangiomatosis, and combinations of lymphatic and other tissue anomalies, including lymphangioleiomyomatosis (LAM). We report a case of a patient with a newly defined entity classified as kaposiform lymphangiomatosis (KLA). This 50-year-old nonsmoking Hispanic woman presented with a 20-year history of cough, hemoptysis, chyloptysis, and pleuritic chest pain. Laboratory evaluation demonstrated a low normal platelet count, elevated d-Dimer, low normal fibrinogen, and elevated fibrin split products. Chest computerized tomography imaging showed enlarged hypodense lymph nodes in the mediastinum and hila, and peribronchovascular thickening, without evidence of cystic parenchymal lesions. Magnetic resonance imaging of the chest showed cystic mediastinal lymph nodes with heterogeneously increased T2 and decreased T1 signal intensity. Fiberoptic bronchoscopy revealed hyperemic mucosa with granular appearance suggestive of a submucosal infiltrative process. Pathological specimens revealed dilated, malformed lymphatic channels within the pleura, pulmonary septa, and bronchovascular bundles, and foci of perilymphatic and intralymphatic spindle cells which reacted with the Prospero homeobox protein 1 (PROX-1) immunostain. The morphology and immunohistochemistry results were consistent with a diagnosis of KLA. This newly recognized clinical-pathological entity among intrathoracic lymphatic anomalies is distinguished from generalized lymphatic anomaly and diffuse pulmonary lymphangiomatosis in part by characteristic hematological abnormalities and hemorrhagic complications, including hemoptysis, as experienced by our patient.