Longitudinally monitored immune biomarkers predict the timing of COVID-19 outcomes.

The clinical outcome of SARS-CoV-2 infection varies widely between individuals. Machine learning models can support decision making in healthcare by assessing fatality risk in patients that do not yet show severe signs of COVID-19. Most predictive models rely on static demographic features and clinical values obtained upon hospitalization. However, time-dependent biomarkers associated with COVID-19 severity, such as antibody titers, can substantially contribute to the development of more accurate outcome models. Here we show that models trained on immune biomarkers, longitudinally monitored throughout hospitalization, predicted mortality and were more accurate than models based on demographic and clinical data upon hospital admission. Our best-performing predictive models were based on the temporal analysis of anti-SARS-CoV-2 Spike IgG titers, white blood cell (WBC), neutrophil and lymphocyte counts. These biomarkers, together with C-reactive protein and blood urea nitrogen levels, were found to correlate with severity of disease and mortality in a time-dependent manner. Shapley additive explanations of our model revealed the higher predictive value of day post-symptom onset (PSO) as hospitalization progresses and showed how immune biomarkers contribute to predict mortality. In sum, we demonstrate that the kinetics of immune biomarkers can inform clinical models to serve as a powerful monitoring tool for predicting fatality risk in hospitalized COVID-19 patients, underscoring the importance of contextualizing clinical parameters according to their time post-symptom onset.

Current Concepts in the Orthopaedic Management of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD), a genetic condition marked by progressive muscle degeneration, presents notable orthopaedic challenges, especially scoliosis, which deteriorates patients' quality of life by affecting sitting balance and complicating cardiac and respiratory functions. Current orthopaedic management strategies emphasize early intervention with corticosteroids to delay disease progression and the use of surgical spinal fusion to address severe scoliosis, aiming to enhance sitting balance, alleviate discomfort, and potentially extend patient lifespan. Despite advancements, optimal management requires ongoing research to refine therapeutic approaches, ensuring improved outcomes for patients with DMD. This review synthesizes recent findings on surgical and nonsurgical interventions, underscoring the importance of a multidisciplinary approach tailored to the dynamic needs of patients with DMD.

Surgical prophylaxis in pediatric orthopedic patients with penicillin allergy: a multicentered retrospective prognostic study.

Up to 20% of orthopedic surgeons still avoid the use of cephalosporins in patients with penicillin allergies despite its reported safety in the adult and general surgery pediatric population. The primary objective is to determine the incidence of adverse effects and allergic reactions when using cephalosporins in pediatric orthopedic patients labeled as penicillin-allergic as compared to those without previously reported penicillin allergy. A multicenter retrospective chart review was performed across three level 1 trauma centers from January 2013 to February 2020 to identify penicillin-allergic as well as non-penicillin-allergic pediatric patients treated for orthopedic injuries. Data were collected regarding patient demographics, antibiotic administered, timing of antibiotic administration, reported drug allergy, and described allergic reaction. Postoperative or intraoperative allergic reactions to antibiotics, surgical site infections, and complications were recorded. A total of 2289 surgeries performed by four fellowship-trained surgeons were evaluated. Eighty-five patients diagnosed with penicillin allergy were identified and underwent 95 surgeries and 95 patients without previously reported penicillin allergy underwent 95 surgeries. One patient, with a documented history of anaphylaxis to cefazolin, sustained an anaphylactic reaction intraoperatively to cefazolin. There were no other reported reactions, surgical site infections, or complications. There was no statistically significant difference in rate of allergic reaction in patients with previously reported penicillin allergy treated with cefazolin and those with no previous reported reaction (P > 0.05). Prophylaxis with cephalosporins is not associated with increased risk for allergic reaction. Cephalosporins can be safely administered to pediatric patients with penicillin allergy undergoing orthopedic intervention. Level of evidence: Level II, Multicenter Retrospective Prognostic Study.

Treatment of severe COVID-19 with convalescent plasma in Bronx, NYC.

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.

QT prolongation in a diverse, urban population of COVID-19 patients treated with hydroxychloroquine, chloroquine, or azithromycin.

PURPOSE: Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients. METHODS: We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias. RESULTS: One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7). Adjusting for race/ethnicity yielded no significant associations. CONCLUSIONS: Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.

Treatment of Severe COVID-19 with Convalescent Plasma in the Bronx, NYC.

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200mL of CCP with a Spike protein IgG titer ≥1:2,430 (median 1:47,385) within 72 hours of admission to propensity score-matched controls cared for at a medical center in the Bronx, between April 13 to May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients <65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients <65 years, but data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy.