Objective To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2associated multisystem inflammatory syndrome in children (MIS-C). Study design Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected. Results Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation. Conclusions Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.
Objectives To describe the clinical manifestations and outcomes of critically ill children with coronavirus disease-19 (COVID-19) in New York City. Study design Retrospective observational study of children 1 month to 21 years admitted March 14 to May 2, 2020, to 9 New York City pediatric intensive care units (PICUs) with severe acute respiratory syndrome coronavirus 2 infection. Results Of 70 children admitted to PICUs, median age was 15 (IQR 9, 19) years; 61.4% male; 38.6% Hispanic; 32.9% black; and 74.3% with comorbidities. Fever (72.9%) and cough (71.4%) were the common presenting symptoms. Twelve patients (17%) met severe sepsis criteria; 14 (20%) required vasopressor support; 21 (30%) developed acute respiratory distress syndrome (ARDS); 9 (12.9%) met acute kidney injury criteria; 1 (1.4%) required renal-replacement therapy, and 2 (2.8%) had cardiac arrest. For treatment, 27 (38.6%) patients received hydroxychloroquine; 13 (18.6%) remdesivir; 23 (32.9%) corticosteroids; 3 (4.3%) tocilizumab; and 1 (1.4%) anakinra; no patient was given immunoglobulin or convalescent plasma. Forty-nine (70%) patients required respiratory support: 14 (20.0%) noninvasive mechanical ventilation, 20 (28.6%) invasive mechanical ventilation (IMV), 7 (10%) prone position, 2 (2.8%) inhaled nitric oxide, and 1 (1.4%) extracorporeal membrane oxygenation. Nine (45%) of the 20 patients requiring IMV were extubated by day 14 with median IMV duration of 218 (IQR 79, 310.4) hours. Presence of ARDS was significantly associated with duration of PICU and hospital stay, and lower probability of PICU and hospital discharge at hospital day 14 ( P < .05 for all). Conclusions Critically ill children with COVID-19 predominantly are adolescents, have comorbidities, and require some form of respiratory support. The presence of ARDS is significantly associated with prolonged PICU and hospital stay.
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks. We have developed a Computational Analysis of Novel Drug Opportunities (CANDO) platform based on the hypothesis that drugs function by interacting with multiple protein targets to create a molecular interaction signature that can be exploited for rapid therapeutic repurposing and discovery. We used the CANDO platform to identify and rank FDA-approved drug candidates that bind and inhibit all proteins encoded by the genomes of five different Ebola virus strains. Top ranking drug candidates for EVD treatment generated by CANDO were compared to in vitro screening studies against Ebola virus-like particles (VLPs) by Kouznetsova et al. and genetically engineered Ebola virus and cell viability studies by Johansen et al. to identify drug overlaps between the in virtuale and in vitro studies as putative treatments for future EVD outbreaks. Our results indicate that integrating computational docking predictions on a proteomic scale with results from in vitro screening studies may be used to select and prioritize compounds for further in vivo and clinical testing. This approach will significantly reduce the lead time, risk, cost, and resources required to determine efficacious therapies against future EVD outbreaks.
Background: Takotsubo cardiomyopathy (TSC) and its complications, such as cardiac rupture (CR), are increasingly being reported in the literature. CR is associated with rapid clinical decline and is uniformly fatal if not surgically repaired. To identify patients who developed CR we performed an analysis of all available indexed cases in the literature and compared them with a control group of patients with TSC without rupture. Hypothesis: Takotsubo cardiomyopathy patients with cardiac rupture do not differ significantly from those without rupture. Methods: MEDLINE (2009) was searched for all TSC case reports with CR. Eleven case reports were identified. Using a random sampling method, we selected 12 case reports of TSC without rupture (control). We included our patient with TSC with rupture as the 12th case of TSC cohort with CR (CR group). Demographic and clinical characteristics were compared between CR group and control. Results: All patients in the TSC group with rupture were female and were significantly older than controls. TSC group with rupture had significantly higher frequency of ST elevation in lead II and absence of T-wave inversion in lead V5 on hospital admission than controls. Mean ejection fraction, systolic blood pressure, and double product, a measure of oxygen demand, was significantly higher in the rupture group compared to controls. The CR group was associated with less frequent use of β-blocker as compared to controls. Conclusions: CR as a complication of TSC could be more common than recognized. Higher double product and ejection fraction suggest higher fluctuation of intracardiac pressure and may cause CR in TSC. Use of β blockers in TSC may provide protection against CR. Methods Ovid MEDLINE (1950-2009) was searched for case reports with search terms ''Takotsubo cardiomyopathy,'' ''Takotsubo syndrome,'' ''stress cardiomyopathy,'' ''ampullary cardiomyopathy,'' and ''broken heart syndrome.'' A total of 375 case reports were identified with ''human'' and ''English'' as limits. Eleven case reports of TSC were identified with CR. All case reports were published during the years 2004 to 2009. To obtain a control group for comparison we searched MEDLINE for case reports with the same search terms spanning 2004 to 2009. We chose a random sampling method using a random number generator to select case reports. If the article matching the random number was not a case
OBJECTIVE: Midline catheters are considered “midway” regarding vascular access. The objective of this systematic review was to explore the current practice, dwell time, and complication rates of midline catheters. DESIGN: Systematic review. SETTING: Search on four databases, PubMed, CINAHL, Scopus, and Embase, were conducted for English language articles published after the year 2000. MEASUREMENTS AND MAIN RESULTS: A total of 987 articles were identified, of which 31 manuscripts met the inclusion criteria and were selected for review. Quality assurance was performed based on the Newcastle-Ottawa score. Average dwell time and complication rates were calculated for studies involving adult patients and adjusted for sample size. This analysis included data from the placement of 18,972 midline catheters across five countries. Aside from two randomized control trials, most of the studies analyzed were cohort studies. One pediatric and two neonatal studies were included. The average dwell time was 16.3 days (n = 4,412). The adjusted mean infection rate was 0.28/1,000 catheter days, with 64% of studies not reporting any infection with midline catheter. The failure rate of midline catheters was 12.5%. Adjusted average rates of other significant complications included the following: deep vein thrombosis (4.1%), dislodgement (5.0%), occlusion (3.8%), phlebitis (3.4%), and infiltration (1.9%). Conclusions: The dwell times and failure rates of midline catheters compare favorably against published data on other types of catheters. Their infection rates are also lower than the reported rates of central venous catheters; however, they have a higher rate of mechanical complications. Active surveillance of infections due to midline catheters is recommended. More data are needed from pediatric and neonatal populations.
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