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Objective: We describe a patient with history of heart transplant on maintenance immunosuppression who presented with sigmoid colon perforation from cytomegalovirus (CMV) colitis and performed a systematic review of outcomes after perforated CMV colitis. Background: Cytomegalovirus enterocolitis is uncommon among solid organ transplant patients and can result in small or large bowel perforation. Methods: We systematically reviewed articles describing patients with CMV enterocolitis with small or large bowel perforations from PubMed, Embase, and Web of Science from database inception to February 2021. Results: Seventy-seven articles were identified containing 84 patients with perforated CMV enterocolitis. The most prevalent comorbid diagnosis was human immunodeficiency virus (HIV; 27 patients, 32%), and 37 patients (44%) were taking corticosteroids at time of presentation. The ileum was the most common location for a perforation (26 patients, 31%). Odds of survival were lower for patients with small bowel perforation (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.14-0.98) and HIV/acquired immunodeficiency syndrome (AIDS; OR, 0.32; 95% CI, 0.11-0.88). Odds of survival were higher for patients with large bowel perforation (OR, 2.64; 95% CI, 1.03-7.09), radiographically diagnosed perforation (OR, 3.45; 95% CI, 1.12-11.60) and those who received a CMV antiviral (OR, 9.19; 95% CI, 3.26-28.48). Conclusions: Perforated CMV enterocolitis is uncommon even in immunocompromised hosts. Clinicians should maintain a high level of suspicion for CMV-induced bowel perforation in this population because antiviral treatment is associated with increased odds of survival.

Background Immunoglobulin A (IgA) is an important component of the early immune response to SARS-CoV-2. Prior serosurveys in high-risk groups employing IgG testing alone have provided discordant estimates. The potential added benefit of IgA in serosurveys has not been established. Methods Longitudinal serosurvey of first responders (police, emergency medical service providers, fire fighters, and other staff) employing 3 serologic tests (anti-spike IgA, anti-spike IgG, and anti-nucleocapsid IgG) correlated with surveys assessing occupational and nonoccupational risk, exposure to COVID-19, and illnesses consistent with COVID-19. Results Twelve percent of first responders in Colorado at baseline and 22% at follow-up were assessed as having SARS-CoV-2 infection. Five percent at baseline and 6% at follow-up were seropositive only for IgA. Among those IgA positive only at baseline, the majority (69%) had a positive antibody at follow-up; 45% of those infected at baseline and 33% at follow-up were asymptomatic. At all time points, the estimated cumulative incidence in our study was higher than that in the general population. Conclusions First responders are at high risk of infection with SARS-CoV-2. IgA testing identified a significant portion of cases missed by IgG testing and its use as part of serologic surveys may improve retrospective identification of asymptomatic infection.

BACKGROUND Swept source optical coherence tomography angiography (SS-OCT-A) choroidal vasculography (CVG) is an imaging method which allows the evaluation of deep choroid details, being a promising too in choroidal pathologies as polypoidal choroidal vasculopathy (PCV). RESEARCH DESIGN AND METHODS Cross-sectional study performed at FOSCAL International Clinic in Colombia. CVG features in patients with PCV were evaluated using SS-OCT CVG. RESULTS Twenty-two eyes of 21 patients were included. The mean age was 72.7 ± 6.5 years old (range: 48.6-95.4 years old). Twelve (57.1%) patients were male. The mean number of polyps detected by SS-OCT-A CVG before treatment with anti-VEGF therapy was 2.04 ± 1.18, which decreased after treatment to 1.18 ± 0.71. This result was statistically significant (p

Background Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear. Methods We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years. Results At baseline, voxel-based analysis showed that higher multimorbidity scores were associated with lower relative activity in orbitofrontal, superior frontal, temporal pole and parahippocampal regions, and greater activity in lateral temporal, occipital, and cerebellar regions. Examination of the individual health conditions comprising the index score showed hypertension and chronic kidney disease individually contributed to the overall multimorbidity pattern of altered activity. Longitudinally, both increases and decreases in activity were seen in relation to increasing multimorbidity over time. These associations were identified in orbitofrontal, lateral temporal, brainstem, and cerebellar areas. Conclusion Together, these results show that greater multimorbidity is associated with widespread areas of altered brain activity, supporting a link between health and changes in aging brain function.

BACKGROUND The ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted both elective and acute medical care. Data from the early months suggest that acute care patient populations deferred presenting to the emergency department (ED), portending more severe disease at the time of presentation. Additionally, care for this patient population trended towards initial non-operative management. AIM To examine the presentation, management, and outcomes of patients who developed gallbladder disease or appendicitis during the pandemic. METHODS A retrospective chart review of patients diagnosed with acute cholecystitis, symptomatic cholelithiasis, or appendicitis in two EDs affiliated with a single tertiary academic medical center in Northern California between March and June, 2020 and in the same months of 2019. Patients were selected through a research repository using international classification of diseases (ICD)-9 and ICD-10 codes. Across both years, 313 patients were identified with either type of gallbladder disease, while 361 patients were identified with acute appendicitis. The primary outcome was overall incidence of disease. Secondary outcomes included presentation, management, complications, and 30-d re-presentation rates. Relationships between different variables were explored using Pearson’s r correlation coefficient. Variables were compared using the Welch’s t-Test, Chi-squared tests, and Fisher’s exact test as appropriate. RESULTS Patients with gallbladder disease and appendicitis both had more severe presentations in 2020. With respect to gallbladder disease, more patients in the COVID-19 cohort presented with acute cholecystitis compared to the control cohort [50% (80) vs 35% (53); P = 0.01]. Patients also presented with more severe cholecystitis in 2020 as indicated by higher mean Tokyo Criteria Scores [mean (SD) 1.39 (0.56) vs 1.16 (0.44); P = 0.02]. With respect to appendicitis, more patients were diagnosed with a perforated appendix at presentation in 2020 [20% (36) vs 16% (29); P = 0.02] and a greater percentage were classified as emergent cases using the emergency severity index [63% (112) vs 13% (23); P < 0.001]. While a greater percentage of patients were admitted to the hospital for gallbladder disease in 2020 [65% (104) vs 50% (76); P = 0.02], no significant differences were observed in hospital admissions for patients with appendicitis. No significant differences were observed in length of hospital stay or operative rate for either group. However, for patients with appendicitis, 30-d re-presentation rates were significantly higher in 2020 [13% (23) vs 4% (8); P = 0.01]. CONCLUSION During the COVID-19 pandemic, patients presented with more severe gallbladder disease and appendicitis. These findings suggest that the pandemic has affected patients with acute surgical conditions.

BACKGROUND AND OBJECTIVE: Neovascularization is a sight-threatening, uncommon complication of posterior uveitis that often goes undetected until persistent clinical findings appear, or in light of treatment failure. This could be attributed to the relative similarity of activity signs in inflammatory neovascular membranes (NVM) and active posterior uveitis. The purpose of the present study is to recognize imaging features that distinguish uveitic neovascularization from active uveitis using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: Cross-sectional study. Patients with posterior uveitis with visual acuity (VA) decrease and at least one of the following findings were assessed by SS-OCTA: retinal thickening, subretinal or intraretinal fluid, and retinal hyperreflective areas. The change of VA and imaging features after treatment with anti-vascular endothelial growth factor (VEGF) therapy were analyzed in cases with inflammatory NVM. RESULTS: Forty-five eyes of 40 patients were evaluated. Twenty-four eyes (53.3%) showed signs of activity, of which eight (33.3%) presented inflammatory NVM. Imaging features that differentiate inflammatory neovascularization from active posterior uveitis included: vitreous cellularity ( P = .003), outer retinal infiltration ( P = .08), choroidal thickness ( P = .003), posterior shadowing ( P = .013), subretinal fluid ( P = .04), and neovascular network ( P ≤ .001). According to NVM characteristics by OCTA, multiple anastomoses and peripheral arcades were visualized at baseline in 85.7% of cases. Mean pre-operative best-corrected VA of inflammatory NVM was 20/150 (logMAR: 0.88 ± 0.60) with significant improvement to 20/40 (logMAR: 0.32 ± 0.22) after anti-VEGF treatment ( P = .027). CONCLUSIONS: SS-OCTA achieves the distinction of inflammatory NVM from active posterior uveitis through specific imaging features. Inflammatory neovascularization presents a suitable response after anti-VEGF therapy. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:129–137.]

Popliteal vein aneurysms are a rare vascular anomaly first reported in the 1980s. Degeneration of elastic fibers and smooth muscle cell reduction, possibly secondary to inflammation, are implicated as integral steps in the development of these aneurysms. Given the rarity of this clinical entity, significant controversy exists regarding ideal treatment strategies, including the role of observation, medical management with anticoagulation, and surgical intervention. Retrospective reviews have demonstrated a failure rate of40% with anticoagulation alone, with patients often presenting with pulmonary embolism. This has prompted our institutional preference for surgical management once the aneurysm is identified. Surgical management involves tangential repair with lateral venorrhaphy most commonly, followed in prevalence by aneurysm resection and end-to-end anastomosis either primarily or with vein interposition. Herein, we report our results with venous plications, through both closed and open techniques.We performed a retrospective review of prospectively collected data for 10 patients undergoing popliteal vein plication for treatment of popliteal vein aneurysms. Patient-level characteristics and operative details were examined from periprocedural and follow-up records.We identified 10 patients undergoing popliteal vein plication, including 9 closed plications and 1 open plication. The average aneurysm size at presentation was 2.35 ± 0.69 cm for closed plication and 4.74 cm for the one open plication. After treatment, the average popliteal vein size was significantly reduced to 1.12 ± 0.45 cm for the closed plications (P .001 from preprocedural size) and 1.13 cm for the open plication with 100% primary patency. Average follow-up for patients treated with closed plication was 35.0 ± 25.2 months, during which seven (78%) patients had a stable, normal popliteal vein size. One patient with recurrence was diagnosed with Klippel-Trénaunay syndrome. The other had degeneration of the popliteal vein cranial to the previous repair at 39 months after the original operation that required additional plication. The open plication patient experienced a hematoma requiring washout and resulting in a transient peroneal mononeuropathy. There was one case of cellulitis after closed plication but no hematomas within this group.Closed plication demonstrated favorable primary patency rates and low recurrence rates, avoiding technical issues or need for early institution of systemic anticoagulation associated with tangential repair and venorrhaphy or resection methods. Closed plication represents an attractive option in patients without luminal thrombus to limit the risk of these postoperative complications and obviates the need for bypass conduit and postoperative anticoagulation.

This retrospective cohort study analyzes venous thromboembolism (VTE) incidence, morbidity, and mortality amongst postsurgical patients with and without VTE chemoprophylaxis within a quality collaborative. Postoperative thromboprophylaxis was broadly applied, yet was associated with no decrease in VTE, without affecting transfusion or mortality. Predictors of breakthrough VTE development despite evidence-based thromboprophylaxis are identified.We hypothesized that a high rate of prescription of VTE chemoprophylaxis would be associated with decreased VTE incidence and mortality.Recommendations for VTE prevention in surgical patients include chemoprophylaxis based upon preoperative risk stratification.This retrospective cohort study analyzed VTE incidence, morbidity, and mortality amongst postsurgical patients with and without VTE chemoprophylaxis between April 2013 and September 2017 from 63 hospitals within the Michigan Surgical Quality Collaborative. A VTE risk assessment survey was distributed to providers. Bivariate and multivariate comparisons were made, as well as using propensity score matched cohorts to determine if VTE chemoprophylaxis was associated with decreased VTE events. Hospitals were compared using risk-reliability adjusted VTE prophylaxis and postoperative VTE event rates.Within the registry, 80% of practitioners reported performing formal VTE risk assessment. Amongst 32,856 operations, there were 480 (1.46%) postoperative VTE, and an overall mortality of 609 (1.85%) patients. Using a propensity matched cohort, we found that rates of VTE were similar in those receiving unfractionated heparin or low molecular weight heparin compared to those not receiving chemoprophylaxis (1.22 vs 1.13%, P = 0.57). When stratified further by VTE risk scoring, even the highest risk patients did not have an associated lower VTE rate (3.68 vs 4.22% P = 0.092). Postoperative transfusion (8.28 vs 7.50%, P = 0.057) and mortality (2.00% vs 1.62%, P = 0.064) rates were similar amongst those receiving and those not receiving chemoprophylaxis. No correlation was found between postoperative VTE chemoprophylaxis application and hospital specific risk adjusted postoperative VTE rates.In modern day postsurgical care, VTE remains a significant occurrence, despite wide adoption of VTE risk assessment. Although postoperative VTE chemoprophylaxis was broadly applied, after adjusting for confounders, no reduction in VTE was observed in at-risk surgical patients.

Objective The aim of the study was to examine the ability of overreading of computed tomography (CT) and right lower quadrant ultrasound (RLQ US) to diagnose appendicitis for children with suspected appendicitis with equivocal CTs at community hospitals. Methods This was a retrospective chart review of all children transferred to a children's hospital from community emergency departments with suspected appendicitis over 2 years for whom both CT and RLQ US were performed. Results One hundred eighty-four children were included with a median age of 10.8 years, and 57.6% were female. Community hospitals documented that CTs were equivocal for appendicitis in 110 (59.8%), positive in 63 (34.2%), and negative in 11 (6.0%). Ninety-seven CTs (88.1%) designated equivocal at community hospitals were later deemed interpretable by pediatric radiologists: 21 (19.1%) as appendicitis and 76 (69.1%) as normal. In 13 children (11.8%), both the community and children's hospital CT interpretations were equivocal. In equivocal cases, RLQ US was consistent with appendicitis in 6 (46.2%), normal in 5 (41.7%), and nondiagnostic in 2. κ value between CT interpretations at community versus children's hospital was 0.13 (95% confidence interval, 0.05-0.22), and κ value between CT interpretation at the children's hospital and RLQ US was 0.59 (95% confidence interval, 0.48-0.70). Conclusions Most CTs deemed equivocal for appendicitis at community hospitals were interpretable by pediatric radiologists. In a few children for whom CTs were designated nondiagnostic, RLQ US provided a definitive diagnosis in almost 90% of cases. The first step in evaluation of children with suspected appendicitis for whom outside CTs are deemed equivocal should be to have the study reinterpreted by a pediatric radiologist.

BACKGROUND: Pediatric surgery (PS) is among the most competitive fellowship opportunities for general surgery residents. Prior investigations into factors associated with successful matriculation to PS have relied on surveys, which have inherent biases. STUDY DESIGN: Data were extracted from the Electronic Residency Application System for applicants from 2012 to 2017 and analyzed after stratification by matriculation status. RESULTS: Data were gathered on a total of 444 applicants, of which 238 matriculated. The applicant pool was predominantly Caucasian (63.5%), largely graduated from US allopathic school (81%) and had a slight male predominance (54%), although the number of female applicants increased significantly over the study period. Attendance at a US allopathic medical school (OR=4.55, p

Introduction Physical inactivity, high screen time, and short sleep are targets of public health initiatives for children. However, few data exist on how many U.S. children meet guidelines for these behaviors—data vital to inform which needs greater targeting. This study describes national prevalence estimates of U.S. children who meet physical activity, screen time, and sleep guidelines alone or in combination across each childhood year. Methods This analysis (completed in 2019) used cross-sectional data from the 2016–2017 National Survey of Children's Health, a nationally representative sample of U.S. children. Child physical activity (days per week with ≥60 minutes), recreational screen time (hours per day of TV viewing and electronic device use), and sleep duration (hours per day) were assessed through parental report. Guidelines recommend ≥60 minutes per day of physical activity, ≤2 hours per day of screen time, and 9–12 hours per day of sleep for individuals aged 6–12 years (8–10 hours for those aged 13–17 years). Results Only 8.8% (95% CI=8.2%, 9.5%) of U.S. children meet all the 3 guidelines combined. Majority of children/adolescents attain the sleep guideline (86.0%, 95% CI=85.2%, 86.7%), but a lower proportion meet physical activity (23.0%, 95% CI=22.1%, 23.9%) or screen time (32.9%, 95% CI=31.9%, 33.8%) guidelines. A substantial age effect was identified, with prevalence of meeting each distinct guideline and all the 3 declining with age (p Conclusions Few U.S. children meet all the 3 movement guidelines, with prevalence rates of children meeting guidelines declining with age. Although many meet sleep guidelines, few meet physical activity or screen time guidelines. Initiatives targeting physical activity and screen time, especially for adolescents, should be pursued.

Globally, tuberculosis (TB) is the leading cause of infectious disease mortality; however, clinicians in the United States are increasingly unfamiliar with TB and the recommended tests and treatment for latent TB infection. Compared with adults, children who develop TB more often develop severe disease, and children < 2 years are particularly susceptible to developing TB disease after initial infection. Nurse practitioners who work in primary care are on the front lines of identifying children at high risk and obtaining testing and treatment. This article reviews the clinical course for identifying children at risk for TB and provides updated guidelines for testing and treatment.

Background During adolescence, childhood and adult forms of tuberculosis (TB) overlap, resulting in diverse disease manifestations. Knowing which patient characteristics are associated with which manifestations may facilitate diagnosis and enhance understanding of TB pathophysiology. Methods In this cross-sectional study, we included 10–19-year-olds in Ukraine's national TB registry who started TB treatment between 2015 and 2018. Using multivariable regression, we estimated associations between patient characteristics and four presentations of TB: pleural, extrathoracic, cavitary and rifampicin-resistant (RR). We also described the epidemiology of adolescent TB in Ukraine. Results Among 2491 adolescent TB cases, 88.4% were microbiologically confirmed. RR-TB was confirmed in 16.9% of new and 29.7% of recurrent cases. Of 88 HIV-infected adolescents, 59.1% were not on antiretroviral therapy at TB diagnosis. Among 10–14-year-olds, boys had more pleural disease (adjusted OR (aOR) 2.12, 95% CI: 1.08–4.37). Extrathoracic TB was associated with age 15–19 years (aOR 0.26, 95% CI: 0.18–0.37) and HIV (aOR 3.25, 95% CI: 1.55–6.61 in 10–14-year-olds; aOR 8.18, 95% CI: 3.58–17.31 in 15–19-year-olds). Cavitary TB was more common in migrants (aOR 3.53, 95% CI: 1.66–7.61) and 15–19-year-olds (aOR 4.10, 95% CI: 3.00–5.73); among 15–19-year-olds, it was inversely associated with HIV (aOR 0.32, 95% CI: 0.13–0.70). RR-TB was associated with recurrent disease (aOR 1.87, 95% CI: 1.08–3.13), urban residence (aOR 1.27, 95% CI: 1.01–1.62) and cavitation (aOR 2.98, 95% CI: 2.35–3.78). Conclusions Age, sex, HIV and social factors impact the presentation of adolescent TB. Preventive, diagnostic and treatment activities should take these factors into consideration., Analysing 2491 cases of adolescent tuberculosis in Ukraine, associations were observed between four clinical presentations – cavitary, pleural, extrathoracic and rifampicin-resistant TB – and age, sex, HIV status, prior treatment and social factors. https://bit.ly/2XplZFt

ObjectiveTo determine the interobserver agreement of history and physical examination findings in children undergoing evaluation in the emergency department (ED) for headaches.Study designWe conducted a prospective, cross-sectional study of children aged 2-17years evaluated at 3 tertiary-care pediatric EDs for non-traumatic headaches. Two clinicians independently completed a standardized assessment of each child and documented the presence or absence of history and physical examination variables. Unweighted κ statistics were determined for 68 history and 24 physical examination variables.ResultsWe analyzed 191 paired observations; median age was 12years, with 19 (9.9%) children younger than 7years. Interrater reliability was at least moderate (κ≥0.41) for 41 (60.3%) patient history variables. Eleven (61.1%) of 18 physical examination variables for which κ statistics could be calculated had a κ that was at least moderate.ConclusionsA substantial number of history and physical examination findings demonstrated at least moderate κ statistic values when assessed in children with headaches in the ED. These variables may be generalizable across different types of clinicians for evaluation of children with headaches. If also found to predict the presence or absence of emergent intracranial abnormalities, the more reliable clinical findings may be helpful in the development of clinical prediction rules or risk stratification models that could be used across settings for children with headaches.

The cross-stressor adaptation hypothesis of exercise training has not been investigated under real-life conditions. Using ecological momentary assessment (EMA), we tested whether usual exercise level moderates the relationship of self-reported anxiety to concurrent ambulatory heart rate (HR) and systolic/diastolic blood pressure (SBP/DBP). Participants (N=832) completed 24-hour ambulatory monitoring of HR/BP, using a brachial BP cuff that took readings at 28-minute intervals. Anxiety levels were concurrently reported on a visual analog scale (VAS) using a Palm Pilot. Usual exercise behavior was assessed by a self-report questionnaire. Random coefficients linear regression models predicting momentary HR/BP readings from time-matched anxiety scores were estimated, yielding the average within-person effect (slope) of anxiety. The interaction of exercise level (i.e., no weekly exercise, 1–149, and ≥150 minutes/week; a between-person factor) with anxiety was added to the model in order to estimate the average anxiety slope for participants in each exercise category. The relationship of HR/BP to anxiety did not differ significantly among exercise categories, hence not providing evidence for the cross-stressor hypothesis. In an exploratory analysis of the difference in HR/BP between occasions when anxiety was in the top versus bottom person-specific quintiles of responses, the difference in HR (but not SBP or DBP) varied significantly by exercise level (F(2,625)=4.92, p=0.008). Though our pre-specified analysis did not support the hypothesis, we provide some post-hoc evidence supporting the cross-stressor hypothesis of exercise training for the HR response to anxiety.

Background A "champagne tap" is a lumbar puncture with no cerebrospinal fluid (CSF) red blood cells (RBCs). Clinicians disagree whether the absence of CSF white blood cells (WBCs) is also required. Aims As supervising providers frequently reward trainees after a champagne tap, we investigated how varying the definition impacted the frequency of trainee accolades. Materials & methods We performed a secondary analysis of a retrospective cross-sectional study of infants ≤60 days of age who had a CSF culture performed in the emergency department (ED) at one of 20 centers participating in a Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) endorsed study. Our primary outcomes were a champagne tap defined by either a CSF RBC count of 0 cells/mm3 regardless of CSF WBC count or both CSF RBC and WBC counts of 0 cells/mm3 . Results Of the 23,618 eligible encounters, 20,358 (86.2%) had both a CSF RBC and WBC count obtained. Overall, 3,147 (13.3%) had a CSF RBC count of 0 cells/mm3 and 377 (1.6%) had both CSF WBC and RBC counts of 0 cells/mm3 (relative rate 8.35, 95% confidence interval 7.51 to 9.27). Conclusions In infants, a lumbar puncture with a CSF RBC count of 0 cells/mm3 regardless of the CSF WBC count occurred eight-times more frequently than one with both CSF WBC and RBC counts of 0 cells/mm3 . A broader champagne tap definition would allow more frequent recognition of procedural success, with the potential to foster a supportive community during medical training, potentially protecting against burnout.

Introduction: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). Methods: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. Results: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays.Conclusions: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis. This work was supported by the MOBI-Kids study and the work in this study was obtained from the European Community's Seventh Framework Programme under Grant Agreements Number 226873—the MOBI-Kids Project—and 603794—the GERoNiMO project. Additional funds for the coordination of MOBI-Kids were obtained from the Spanish Ministry of Science and Innovation (MINECO), while complementary funds for the conduct of MOBI-Kids in Spain were obtained from the Spanish Health Research Fund (FIS) of the National Institute for Health Carlos III. Italian participation is partially supported by a Ministry of Health grant (RF-2009-1546284). In Canada, funding was provided by a grant from the Canadian Institutes for Health Research under a peer-reviewed university-industry partnership program that involved the Canadian Wireless Telecommunications Association, who provided technical data on wireless telecommunications practices in Canada. The German study centre received additional support by the Federal Office for Radiation Protection (BfS). Japanese participation in MOBI-Kids was supported by the Ministry of Internal Affairs and Communications. New Zealand participation was supported by Health Research Council and Cure Kids. In France, this study received funds from the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. India received funding from Board of Research in Nuclear Sciences (BRNS). The funding sources had no role in: the study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the article for publication.

Objective Venous thromboembolism (VTE) is a common disease with potentially devastating and long-term sequelae, such as pulmonary embolism and post-thrombotic syndrome (PTS). Given the mortality risk, prevalence of VTE, and limited access to diagnostic imaging, clinically relevant biomarkers for diagnosis and prognostication are needed. Therefore, this review aimed to summarize the data on clinically applicable biomarkers that best indicate acute VTE and chronic PTS. Methods We reviewed the medical and scientific literature from 2001 to 2019 for VTE biomarkers. Randomized controlled trials, meta-analyses, and review articles were included. Primary basic research papers with no clinical applicability, opinion papers, institutional guidelines, and case reports were excluded. Results We highlight the diagnostic value of D-dimer alongside other promising biomarkers, including cellular adhesion molecules, P-selectin, cytokines (interleukins 6 and 10), fibrin monomer complexes, and coagulation factors (factor VIII). Conclusions High-sensitivity D-dimer remains the most clinically established VTE biomarker. Current research endeavors are under way to identify more precise biomarkers of VTE and PTS.

BackgroundData show that a single dose of casirivimab and imdevimab (REGEN-COV®) is effective in treating hospitalized individuals and outpatients with COVID-19 and in post-exposure prophylaxis. We present results from a phase 1, double-blind, placebo-controlled trial evaluating the safety, tolerability, and efficacy of repeat monthly doses of subcutaneous (SC) REGEN-COV in uninfected adult volunteers who were healthy or had chronic stable medical conditions.MethodsSubjects were randomized (3:1) to SC REGEN-COV 1200 mg or placebo dosed every 4 weeks for up to 6 doses. The primary and secondary endpoints evaluated the safety, pharmacokinetics, and immunogenicity of multiple-dose administration of REGEN-COV. Efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion.ResultsIn total, 969 subjects were treated. Repeat monthly dosing of SC REGEN-COV led to a 92.4% relative risk reduction in clinically-defined COVID-19 compared to placebo (3/729 [0.4%] vs 13/240 [5.4%]; odds ratio: 0.07 [95% CI, 0.01–0.27]), and a 100% reduction in laboratory-confirmed COVID-19 (0/729 vs 10/240 [4.2%]; odds ratio 0.00). Development of anti-drug antibodies was low (ConclusionsRepeated monthly administration of 1200 mg SC REGEN-COV was well-tolerated with low immunogenicity, and showed a substantial risk reduction in COVID-19 occurrence.(ClinicalTrials.gov identifier, NCT04519437)

Funding Information This study was supported by Project BIOSAFE funded by FEDER through the Programa Operacional Factores de Competitividade–COMPETE and by Fundação para a Ciência e a Tecnologia (FCT, Portugal)—Grant LISBOA-01-0145-FEDER-030713, PTDC/CAL-EST/30713/2017 and by FCT through funds to GHTM (UID/04413/2020), CIISA Project (UID/CVT/00276/2020), and Project PTDC/CVT-CVT/28469/2017. The contributions of Andrea T. Feßler and Stefan Schwarz were financially supported by the German Federal Ministry of Education and Research (BMBF) under project numbers 01KI1727D and 01KI2009D as part of the Research Network Zoonotic Infectious Diseases. Part of this research was supported by Cost Action CA18217: European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT). Apramycin and florfenicol are two antimicrobial agents exclusively used in veterinary medicine. Resistance determinants to these antimicrobial agents have been described in several staphylococci, yet no inhibition zone-based epidemiological cutoff (ECOFF) values are available to detect populations harboring resistance mechanisms. In this study, we propose disk diffusion inhibition zone ECOFF values of Staphylococcus aureus for apramycin and florfenicol. The susceptibility to apramycin and florfenicol was evaluated by disk diffusion of five S. aureus collections, comprising 352 isolates of animal (n = 265) and human (n = 87) origin. The aggregated distributions of inhibition zone diameters were analyzed by the normalized resistance interpretation method to obtain normalized wild-type (WT) population distributions and corresponding ECOFF values. The putative WT populations of S. aureus were characterized by an inhibition zone ≥15 mm (ECOFF = 15 mm) for apramycin and ≥21 mm for florfenicol (ECOFF = 21 mm). Five nonwild-type (NWT) isolates were detected for apramycin, all without inhibition zone and harboring the apmA gene, whereas five NWT isolates were identified for florfenicol, all carrying the fexA gene. The proposed ECOFF values for apramycin and florfenicol may be a valuable tool in future antimicrobial resistance monitoring and surveillance studies to identify S. aureus NWT populations toward these antimicrobial agents. publishersversion published

SummaryBackgroundThe monoclonal antibody combination casirivimab and imdevimab (REGEN-COV®) reduced viral load, hospitalisation, or death when administered 1:1 as an intravenous (IV) dose ≥1200 mg in a phase 3 COVID-19 outpatient study. Availability of subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients.MethodsThis is a double-blind, placebo-controlled study of SARS-CoV-2-infected outpatients who were asymptomatic, or symptomatic but without risk factors for severe COVID-19. Patients were randomised to single IV dose (517 patients) of REGEN-COV 300, 600, 1200 or 2400 mg or placebo; or a single SC dose (286 patients) of REGEN-COV 600 or 1200 mg or placebo. The primary endpoint was time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative to SARS-CoV-2 at baseline.FindingsAll REGEN-COV treatments showed significant (p10 copies/mL. Each REGEN-COV treatment showed significant (pInterpretationIn asymptomatic and low-risk symptomatic SARS-CoV-2-infected outpatients seronegative for antibodies against SARS-CoV-2 at baseline, REGEN-COV significantly and comparably reduced viral load at all IV and SC doses.FundingRegeneron Pharmaceuticals, Inc. and Hoffman-La RocheRESEARCH IN CONTEXTEvidence before this studyEarly phase 1/2 data in coronavirus disease 2019 (COVID-19) outpatients (NCT04425629) found that the REGEN-COV® antibody combination, casirivimab and imdevimab, administered 1:1 as a single intravenous (IV) dose of 2400 mg or 8000 mg significantly reduced viral load over the first week compared to placebo. Enhanced viral clearance was more pronounced in patients who were seronegative for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or who had high viral load at baseline. The phase 3 portion of this outpatient treatment study subsequently evaluated 1200 mg IV and 2400 mg IV doses, demonstrating consistent virologic efficacy, further demonstrating that REGEN-COV treatment reduced risk of COVID-19-related hospitalisation or all-cause death, and shortened time to symptom resolution. Virologic clearance was similar among those treated with any of the three doses (8000 mg, 2400 mg, or 1200 mg); therefore, maximal virologic efficacy may have been achieved at the 1200 mg dose in this treatment setting. These results warranted investigation of lower dose regimens.Added value of this studyThe present dose-ranging study evaluated whether a lower dose regimen could demonstrate virologic efficacy similar to that observed with 1200 mg IV and 2400 mg IV doses in outpatient treatment study. Exploration of a wider dose range will provide further characterisation of the clinical effects of REGEN-COV. Moreover, identifying a lower efficacious dose could bolster the ability to provide an adequate therapeutic supply of REGEN-COV in the setting of a global pandemic. A 1200 mg subcutaneous (SC) dose of REGEN-COV also prevented COVID-19 in household contacts of SARS-CoV-2-infected individuals (NCT04452318). The availability of a SC regimen could improve access for patients who have confirmed SARS-CoV-2 infection but for who IV infusion is not feasible.Implications of all the available evidenceDespite the growing number of therapeutics with authorisation or approval for the treatment and/or prevention of COVID-19, there remains a significant global need for effective COVID-19 therapies. Additional therapeutics and dosing regimens will be required to meet demand and to meet the needs of specific patient populations. Lower IV doses of REGEN-COV, and the option of SC administration, should increase accessibility for patients. This increased availability needs to be weighed against several unanswered questions, including 1) whether the correlation between decreased viral load in the nasopharynx and improvement in clinical outcome holds at lower doses of REGEN-COV, and 2) whether the reduced drug exposure margins are sufficient to prevent viral escape and emergence of variants of concern.

Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)—with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20–42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score −0.85, 95% CI −1.39 to −0.33) compared to controls (mean 0.67, 95% CI −0.21 to 1.57, p &lt, 0.01). In univariate analysis, the presence of hypogonadism (β −1.50, p &lt, 0.01), high c-PWV (β −0.35, p = 0.09), and high AGEs (β −1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β −1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p &lt, 0.01). Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. Trial Registration: NCT02572934.

Background and Purpose: We examined differences in the volume and pattern of physical activity (PA) and sedentary behavior between adults with and without stroke. Methods: We studied cohort members with an adjudicated or self-reported stroke (n=401) and age-, sex-, race-, region of residence-, and body mass index-matched participants without a history of stroke (n=1203) from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Sedentary behavior (total volume and bouts), light-intensity PA, and moderate-to-vigorous-intensity PA were objectively measured for 7 days via hip-worn accelerometer. Results: Sedentary time (790.5±80.4 versus 752.4±81.9 min/d) and mean sedentary bout duration (15.7±12.6 versus 11.9±8.1 min/d) were higher and PA (light-intensity PA: 160.5±74.6 versus 192.9±73.5 min/d and moderate-to-vigorous-intensity PA: 9.0±11.9 versus 14.7±17.0 min/d) lower for stroke survivors compared with controls ( P P Conclusions: Stroke survivors accrued a lower volume of PA, higher volume of sedentary time, and exhibited accrual patterns of more prolonged sedentary bouts and shorter, lower intensity activity breaks compared with persons without stroke.

Background: Timely detection of early microvascular changes in patients with prediabetes could help reduce the likelihood of progression of diabetes-related retinal complications. Aim: To determine early microvascular changes in patients with prediabetes using optical coherence tomography angiography (OCT-A). Methods: In this single-center retrospective case-control study, macular OCT-A images of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed in non-diabetic controls, and prediabetic and diabetic subjects. A quantitative analysis was performed using ImageJ software of the foveal avascular zone (FAZ) area, acircularity index (AI), perfusion density (PD), and vascular length density (VLD). Results: A total of 94 eyes of 53 patients were included in this study. The global mean age was 57.7 years, 39.6% men and 60.4% women. In SCP, the mean PD was 0.283 ± 0.15, 0.186 ± 0.720, and 0.186 ± 0.07 in non-diabetic controls, and prediabetic and diabetic groups, respectively. The mean VLD was 8.728 ± 3.425 in non-diabetic controls, 6.147 ± 1.399 in prediabetic group, and 6.292 ± 1.997 in patients with diabetes. The comparison of prediabetic patients and controls shows statistical differences between PD and VLD in both plexus SCP ( p = 0.002 and p = 0.001, respectively) and DCP ( p = 0.005 and p = 0.002, respectively). The mean area of FAZ in patients with diabetes and normal individuals was 0.281 and 0.196 mm2, respectively ( p Conclusion: PD and VLD demonstrated to be early microvascular changes in prediabetic patients evaluated by OCT-A. No alterations of FAZ were evidenced in this group.

OBJECTIVES To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection. METHODS In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively. RESULTS Of all infants included, 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4–24.5] 28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0–17). Infants with invasive HSV had a higher median score (6, interquartile range: 4–8) than those without invasive HSV (3, interquartile range: 1.5–4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80–0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43). CONCLUSIONS A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.

INTRODUCTIONLittle is known about longitudinal decline in white matter (WM) microstructure and its associations with cognition in preclinical Alzheimer’s disease (AD).METHODSLongitudinal diffusion tensor imaging and neuropsychological testing from 50 older adults who subsequently developed mild cognitive impairment or dementia (subsequently impaired, SI) and 200 cognitively normal controls. Rates of WM decline were compared between groups using voxel-wise linear mixed-effects models. Associations between change in WM and cognition were examined.RESULTSSI had faster decline in fractional anisotropy (FA) in the right inferior fronto-occipital fasciculus (R.IFOF) and bilateral splenium of the corpus callosum. Decline in R.IFOF FA was related to decline in verbal memory, visuospatial ability, processing speed, and MMSE (p≤ 0.05). Decline in bilateral splenium FA was related to decline in verbal fluency, processing speed, and MMSE (p≤ 0.05).DISCUSSIONAccelerated regional WM decline is characteristic of preclinical AD and related to domain specific cognitive decline.

OBJECTIVES Serious bacterial infections (SBIs) in young infants can present with fever or hypothermia. There are substantial data on fever as a presentation for SBI that help to inform the clinical approach. In contrast, data on hypothermia are lacking, thus leaving clinicians without guidance. We aimed to describe the workup and findings, specifically the occurrence, of SBIs in infants younger than 60 days of life with hypothermia. METHODS We reviewed the medical records of infants younger than 60 days of life with rectal temperature of less than 36.5°C upon arrival to a children's hospital emergency department between January 2013 and December 2014. Comparisons were made between those who were found to have an SBI and those without. Serious bacterial infection was defined as bacteremia, bacterial meningitis, pneumonia, or urinary tract infection (UTI). RESULTS From the 414 patients identified, 104 (25%) underwent a sepsis evaluation of blood, urine, and/or cerebrospinal fluid culture. Serious bacterial infections were identified in 9 patients: 4 with UTI, 1 with pneumonia, 2 with bacteremia, 1 with pneumonia and UTI, and 1 with meningitis and bacteremia. Compared with patients with negative cultures, patients with SBI were older and had elevated absolute band counts and elevated immature-to-total neutrophil ratio. CONCLUSIONS Approximately a quarter of infants younger than 60 days with hypothermia were evaluated for SBI. Serious bacterial infection was identified in 9% of evaluated infants (2% of all hypothermic infants). Hypothermia can be a presenting sign of SBI.

Objectives Children with obesity may possess unique injury characteristics that may affect their emergency care. To better understand this relationship, we investigated the association of obesity in pediatric trauma patients and intra-abdominal injuries (IAIs) and routinely utilized emergency department (ED) diagnostic procedures (computed tomography (CT) scans and ultrasound (US) examinations). Methods This secondary data analysis utilized Pediatric Emergency Care Applied Research Network (PECARN) data from 2007 to 2010. Since height data were not available, children (2–17 years) with obesity were defined using weight-for-age percentiles. Non-parametric testing determined potential confounders. Adjusted odds ratios (aOR) were calculated using binary logistic regression for weight status and IAIs and diagnostic procedures. Results There were 3846 patients with actual weight recorded: 3301 (85.8%) children without obesity and 545 (14.2%) with obesity. Children with obesity had decreased odds for IAI after adjusting for race, mechanical force injury (MFI) type, vomiting, and abdominal wall trauma (adjusted odds ratio (aOR) = 0.58 (95% CI 0.35–0.97); p-value = 0.04). Patients with obesity had reduced odds for a CT examination. No association was found between obesity status and US utilization. African-American patients had decreased odds for IAIs, CT scans and US examinations after adjustment which could be related to MFI type. Conclusions Obesity appears to reduce the odds for pediatric IAIs and CT scans, but not for US examinations. Selection bias is possible due to injury severity and missing or excluded weight data. Further research is needed in other pediatric populations with obesity and blunt injuries.

Introduction: The World Health Organization recently recognized the importance of emergency and trauma care in reducing morbidity and mortality. Training programs are essential to improving emergency care in low-resource settings; however, a paucity of comprehensive curricula focusing specifically on pediatric emergency medicine (PEM) currently exists. The African Federation for Emergency Medicine (AFEM) developed a PEM curriculum that was pilot-tested in a non-randomized, controlled study to evaluate its effectiveness in nurses working in a public Tanzanian referral hospital. Methods: Fifteen nurses were recruited to participate in a two-and-a-half-day curriculum of lectures, skill sessions, and simulation scenarios covering nine topics; they were matched with controls. Both groups completed pre- and post-training assessments of their knowledge (multiple-choice test), self-efficacy (Likert surveys), and behavior. Changes in behavior were assessed using a binary checklist of critical actions during observations of live pediatric resuscitations. Results: Participant-rated pre-training self-efficacy and knowledge test scores were similar in both control and intervention groups. However, post-training, self-efficacy ratings in the intervention group increased by a median of 11.5 points (interquartile range [IQR]: 6-16) while unchanged in the control group. Knowledge test scores also increased by a median of three points (IQR: 0-4) in the nurses who received the training while the control group’s results did not differ in the two periods. A total of 1192 pediatric resuscitation cases were observed post-training, with the intervention group demonstrating higher rates of performance of three of 27 critical actions. Conclusion: This pilot study of the AFEM PEM curriculum for nurses has shown it to be an effective tool in knowledge acquisition and improved self-efficacy of pediatric emergencies. Further evaluation will be needed to assess whether it is currently effective in changing nurse behavior and patient outcomes or whether curricular modifications are needed.

OBJECTIVE To assess the clinical accuracy of 2 serum-based assays and 1 saliva-based assay for detection of adverse food reaction (AFR) in dogs without clinical signs of disease. ANIMALS 30 healthy client-owned dogs. PROCEDURES Dog owners completed an online survey to collect comprehensive information about their pets' diet history. From each dog, serum and saliva samples were obtained and submitted for AFR testing by means of 3 assays that assessed the immunoglobulin response to 24 foods. Assays A and B measured food allergen–specific IgE concentrations in serum, whereas assay C measured food allergen–specific IgA and IgM concentrations in saliva. Descriptive data were generated, and Fisher exact tests were used to assess the respective associations between positive test results and specific food ingredients to which dogs were exposed. RESULTS Assays A, B, and C yielded positive results for 26, 18, and 30 dogs, respectively. All dogs had positive results for at least 1 assay. The median (range) number of foods or ingredients to which dogs tested positive was 10.5 (0 to 24) for assay A, 1 (0 to 13) for assay B, and 12.5 (4 to 22; IgM) and 3 (0 to 24; IgA) for assay C. Positive test results were not significantly associated with prior food exposure. CONCLUSIONS AND CLINICAL RELEVANCE Saliva and serum assays for AFR often yielded positive results for apparently healthy dogs and are not recommended for clinical use. Elimination diet trials remain the gold standard for diagnosis of AFR in dogs.

Background Pediatric acute kidney injury (AKI) is associated with long-term morbidity and mortality; however, outcomes improve when AKI is detected earlier. Current definitions of AKI use baseline creatinine; community-acquired AKI (CA-AKI) is difficult to define and detect in the pediatric emergency department (ED) when no baseline creatinine is available. Our objective was to compare age- and gender-based creatinine norms to the traditional baseline (lowest creatinine in previous 3 months) to diagnose CA-AKI. Methods This was a retrospective cross-sectional study conducted in children 1 month-18 years of age seen in the pediatric ED in whom a creatinine was obtained. Results Per the Kidney Disease Improving Global Outcomes AKI definition in encounters with baseline creatinine available, 343/2338 (14.7%) had CA-AKI. When the upper limit of the age- and gender-based creatinine norm was applied as a surrogate baseline creatinine, CA-AKI was diagnosed in 1.5% of encounters (239/15,486). Additionally, CA-AKI was diagnosed in 178 cases using the upper limit of age- and gender-based creatinine norms only, as these cases did not have a baseline creatinine. Conclusions Age- and gender-based creatinine norms can be applied as a surrogate baseline to detect CA-AKI in all children regardless of whether baseline creatinine is available, potentially detecting it earlier.

Assessment of treating metastatic ileal neuroendocrine tumors (NETs) with complete resection of primary tumor, nodal and liver metastases, plus administration of long-acting somatostatin analogues (SSAs). A prospective database was queried for patients with ileal or pancreatic NETs with pathology-confirmed liver metastases and tumor somatostatin receptors. Patients did not have MEN-1 and had no previous treatment. The impacts of SSA treatment on the primary outcome of survival and secondary outcome of progression-free survival were assessed with Kaplan–Meier analysis. Log rank test was used to compare overall and progression-free survival among groups. Seventeen ileal NET patients and 36 pancreatic NET patients who underwent surgical resection between 2001 and 2018, who had pathology-confirmed liver metastases and confirmed tumor somatostatin receptors, did not have MEN-1, and had no previous treatment were identified. Median follow-up for patients with ileal NETs was 80 months (range 0–197 months) and 32 months (range 1–182 months) for pancreatic NETs. Five-year survival was 93% and 72% for ileal and pancreatic NET, respectively. Progression-free 5-year survival was 70% and 36% for ileal and pancreatic NET, respectively. Overall 5-year survival for pNETs was greater in those patients treated with SSA (79%) compared to those who underwent surgery alone (34%, p

Background Diabetic ketoacidosis (DKA) is a common complication affecting patients with type 1 diabetes, and DKA is associated with dehydration and electrolyte abnormalities. Supraventricular tachycardia (SVT), although a common tachydysrhythmia in the pediatric population, remains a rare entity in patients presenting with DKA. Case Report We describe a case of first-time SVT in an adolescent patient with DKA and recent methamphetamine abuse, with both factors likely predisposing him to develop a tachydysrhythmia. Why Should an Emergency Physician Be Aware of This? SVT can be present in a patient who has concomitant recent stimulant intake and DKA. A trial of abortive therapy, such as adenosine, should be considered upon diagnosis.

In this retrospective study, we assessed the safety of window period prophylaxis and proportion of tuberculin skin test (TST) conversions in children

Background International guidelines recommend monitoring weight as an indicator of therapeutic response in childhood tuberculosis (TB) disease. This recommendation is based on observations in adults. In the current study, we evaluated the association between weight change and treatment outcome, the accuracy of using weight change to predict regimen efficacy, and whether successfully treated children achieve catch-up weight gain. Methods We enrolled children treated for drug-susceptible TB disease (group 1) and multidrug-resistant TB disease (group 2) in Peru. We calculated the change in weight-for-age z score (ΔWAZ) between baseline and the end of treatment months 2–5 for group 1, and between baseline and months 2–8 for group 2. We used logistic regression and generalized estimating equation models to evaluate the relationship between ΔWAZ and outcome. We plotted receiver operating characteristic curves to determine the accuracy of ΔWAZ for predicting treatment failure or death. Results Groups 1 and 2 included 100 and 94 children, respectively. In logistic regression, lower ΔWAZ in months 3–5 and month 7 was associated with treatment failure or death in groups 1 and 2, respectively. In generalized estimating equation models, children in both groups who experienced treatment failure or death had lower ΔWAZ than successfully treated children. The ΔWAZ predicted treatment failure or death with 60%–90% sensitivity and 60%–86% specificity in months 2–5 for group 1 and months 7–8 for group 2. All successfully treated children—except group 2 participants with unknown microbiologic confirmation status—achieved catch-up weight gain. Conclusions Weight change early in therapy can predict the outcome of childhood TB treatment.

The optimal medical management of patients following endovascular deep venous interventions remains ill-defined. As such, the Society of Interventional Radiology Foundation (SIRF) convened a multidisciplinary group of experts in a virtual Research Consensus Panel (RCP) to develop a prioritized research agenda regarding antithrombotic therapy following deep venous interventions. The panelists presented the gaps in knowledge followed by discussion and ranking of research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were identified as high priority: 1) characterization of biological processes leading to in-stent stenosis/rethrombosis; 2) identification and validation of methods to assess venous flow dynamics and their effect on stent failure; 3) elucidation of the role of inflammation and anti-inflammatory therapies; and 4) clinical studies to compare antithrombotic strategies and improve venous outcome assessment. Collaborative, multicenter research is necessary to answer these questions and thereby enhance the care of patients with venous disease.

OBJECTIVES Describe the clinical presentation, prevalence, and outcomes of concurrent serious bacterial infection (SBI) among infants with mastitis. METHODS Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants aged ≤90 days with mastitis who were seen in the emergency department between January 1, 2008, and December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS Among 657 infants (median age 21 days), 641 (98%) were well appearing, 138 (21%) had history of fever at home or in the emergency department, and 63 (10%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 581 (88%), 274 (42%), and 216 (33%) infants, respectively. Pathogens grew in 0.3% (95% confidence interval [CI] 0.04–1.2) of blood, 1.1% (95% CI 0.2–3.2) of urine, and 0.4% (95% CI 0.01–2.5) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 335 (51%) infants, with 77% (95% CI 72–81) growing a pathogen, most commonly methicillin-resistant Staphylococcus aureus (54%), followed by methicillin-susceptible S aureus (29%), and unspecified S aureus (8%). A total of 591 (90%) infants were admitted to the hospital, with 22 (3.7%) admitted to an ICU. Overall, 10 (1.5% [95% CI 0.7–2.8]) had sepsis or shock, and 2 (0.3% [95% CI 0.04–1.1]) had severe cellulitis or necrotizing soft tissue infection. None received vasopressors or endotracheal intubation. There were no deaths. CONCLUSIONS In this multicenter cohort, mild localized disease was typical of neonatal mastitis. SBI and adverse outcomes were rare. Evaluation for SBI is likely unnecessary in most afebrile, well-appearing infants with mastitis.

Background REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. Methods We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-COV-2 infection (as measured by reverse-transcriptase–quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). Results Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. Conclusions Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.)

ImportanceEasy-to-administer antiviral treatments may be used to prevent progression from asymptomatic infection to COVID-19 and to reduce viral carriage.ObjectiveEvaluate the efficacy and safety of subcutaneous casirivimab and imdevimab antibody combination (REGEN-COV) to prevent progression from early asymptomatic SARS-CoV-2 infection to COVID-19.DesignRandomized, double-blind, placebo-controlled, phase 3 study that enrolled asymptomatic close contacts living with a SARS-CoV-2–infected household member (index case). Participants who were SARS-CoV-2 RT-qPCR–positive at baseline were included in the analysis reported here.SettingMulticenter trial conducted at 112 sites in the United States, Romania, and Moldova.ParticipantsAsymptomatic individuals ≥12 years of age were eligible if identified within 96 hours of collection of the index case’s positive SARS-CoV-2 test sample.InterventionsA total of 314 asymptomatic, SARS-CoV-2 RT-qPCR–positive individuals living with an infected household contact were randomized 1:1 to receive a single dose of subcutaneous REGEN-COV 1200mg (n=158) or placebo (n=156).Main Outcome(s) and Measure(s)The primary endpoint was the proportion of participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy endpoints were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Safety was assessed in all treated participants.ResultsSubcutaneous REGEN-COV 1200mg significantly prevented progression from asymptomatic to symptomatic disease compared with placebo (31.5% relative risk reduction; 29/100 [29.0%] vs 44/104 [42.3%], respectively; P=.0380). REGEN-COV reduced the overall population burden of high–viral load weeks (39.7% reduction vs placebo; 48 vs 82 total weeks; P=.0010) and of symptomatic weeks (45.3% reduction vs placebo; 89.6 vs 170.3 total weeks; P=.0273), the latter corresponding to an approximately 5.6-day reduction in symptom duration per symptomatic participant. Six placebo-treated participants had a COVID-19–related hospitalization or ER visit versus none for those receiving REGEN-COV. The proportion of participants receiving placebo who had ≥1 treatment-emergent adverse events was 48.1% compared with 33.5% for those receiving REGEN-COV, including events related (39.7% vs 25.8%, respectively) or not related (16.0% vs 11.0%, respectively) to COVID-19.Conclusions and RelevanceSubcutaneous REGEN-COV 1200mg prevented progression from asymptomatic SARS-CoV-2 infection to COVID-19, reduced the duration of high viral load and symptoms, and was well tolerated.Trial RegistrationClinicalTrials.gov Identifier, NCT04452318KEY POINTSQuestionCan treatment with the anti–SARS-CoV-2 antibody combination REGEN-COV prevent COVID-19 and reduce viral load when given to recently exposed and asymptomatic individuals?FindingsIn this randomized, double-blind, phase 3 trial, subcutaneously administered REGEN-COV 1200 mg significantly reduced progression of asymptomatic SARS-CoV-2 infection to symptomatic infection (ie, COVID-19) by 31.5% compared with placebo. REGEN-COV also reduced the overall population burden of high viral load weeks (39.7% reduction vs placebo; 48 vs 82 total weeks; P=.0010).MeaningIn the current pandemic, utilization of subcutaneous REGEN-COV prevents progression of early asymptomatic infection to COVID-19 and reduces viral carriage.

BackgroundContinued SARS-CoV-2 infections and COVID-19-related hospitalizations highlight the need for effective anti-viral treatments in the outpatient setting. In a descriptive interim analysis of the phase 1/2 portion of a double-blind phase 1/2/3 trial in COVID-19 outpatients conducted between June 16, 2020 and September 4, 2020, REGEN-COV® (casirivimab plus imdevimab) antibody combination reduced SARS-CoV-2 viral load versus placebo.MethodsThis final phase 1/2 analysis comprises 799 outpatients, including 275 from the previous descriptive analysis (group-1) and 524 from phase 2 (group-2). Patients were randomized (1:1:1) to placebo, REGEN-COV 2400mg, or REGEN-COV 8000mg. Prespecified hierarchical analyses of virologic endpoints were performed in group-2. The proportion of patients with ≥1 COVID-19–related medically attended visit (MAV) through day 29 was assessed in group-1+2. Efficacy was assessed in patients confirmed SARS-CoV-2–positive by baseline nasopharyngeal RT-qPCR. Safety was assessed in all treated patients.ResultsData from 799 outpatients enrolled from June 16, 2020 to September 23, 2020 are reported. Time-weighted average daily reduction in viral load through day 7 was significantly greater in the REGEN-COV combined 2400mg+8000mg group versus placebo in patients with baseline viral load >107 copies/mL (prespecified primary endpoint): -0.68 log10 copies/ml (95% CI, -0.94 to -0.41; PPP=.0003) log10 copies/mL in serum antibody–negative patients and in the overall population, respectively. REGEN-COV reduced the proportion of patients with ≥1 COVID-19–related MAV versus placebo (2.8% [12/434] REGEN-COV combined dose group versus 6.5% [15/231] placebo; P=.024; relative risk reduction [RRR]=57%); in patients with ≥1 risk factor for hospitalization, the treatment effect was more pronounced (RRR=71%). Adverse events were similar across groups.ConclusionsIn COVID-19 outpatients enrolled prior to the widespread circulation of delta and omicron variants, treatment with REGEN-COV significantly reduced viral load and COVID-19–related MAVs.

Background The CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis Versus Anticoagulation for the Prevention of Post‐Thrombotic Syndrome) trial did not show a reduction of post‐thrombotic syndrome (PTS) after additional ultrasound‐accelerated catheter‐directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1‐year follow‐up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long‐term follow‐up. Methods and Results Patients aged 18 to 85 years with a first‐time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound‐accelerated catheter‐directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow‐up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow‐up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow‐up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [P=0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12‐month follow‐up. Conclusions The impact of additional ultrasound‐accelerated catheter‐directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00970619.

BACKGROUND: Childhood TB cases can be found using passive case finding (PCF), i.e., by diagnosing children presenting with symptoms, or using active case finding (ACF), i.e., by identifying children with TB through contact tracing. Our study determined epidemiologic, clinical, and radiographic differences between these groups.DESIGN/METHODS: Retrospective cohort study of children aged 0–19 years diagnosed with TB from January 1, 2012 to December 31, 2019 at a U.S. TB clinic, comparing clinical, radiographic, microbiologic, and epidemiological characteristics of children identified using PCF and ACF.RESULTS: Of 178 eligible patients, 99 (55.6%) were diagnosed using PCF. Children identified using PCF were older (mean 8.9 vs. 6.1 years, P = 0.003), more often non-US-born (OR 2.29, 95% CI 1.12–4.67), had more extrapulmonary disease (44.4% vs. 3.8%, OR 20.27, 95% CI 5.98–68.64) and severe intrathoracic findings (39.4% vs. 10.1%, OR 5.77, 95% CI 2.50–13.29). Children identified using ACF were often asymptomatic, had isolated hilar/mediastinal adenopathy, but had more availability of drug susceptibility data from a link to a source case.CONCLUSION: Children identified using PCF had more severe manifestations, while those identified using ACF had greater availability of drug susceptibility data. Clinicians should be aware that clinical and radiographic presentations in children identified using PCF and those identified using ACF differ, and that the latter may be eligible for shorter treatment regimens.

BackgroundREGEN-COV antibody cocktail (casirivimab with imdevimab) rapidly reduced viral load and decreased medically-attended visits in the phase 1/2 portion of this trial; REGEN-COV, retains activity in vitro against emerging SARS-CoV-2 variants of concern.MethodsThe phase 3 portion of this adaptive, randomized, master protocol, included 4,057 Covid-19 outpatients with one or more risk factors for severe disease. Patients were randomized to a single treatment of intravenous placebo, or various doses of REGEN-COV, and followed for 28 days. The prespecified hierarchical analysis first compared REGEN-COV 2400mg dose vs concurrent placebo, then compared the 1200mg dose vs concurrent placebo, for endpoints assessing risk of hospitalization or death, and time to symptom resolution. Safety was evaluated in all treated patients.ResultsBoth REGEN-COV 2400mg and 1200mg significantly reduced Covid-19-related hospitalization or all-cause death compared to placebo (71.3% reduction [1.3% vs 4.6%; pConclusionsTreatment with REGEN-COV was well-tolerated and significantly reduced Covid-19-related hospitalization or all-cause death, rapidly resolved symptoms, and reduced viral load.(Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)

Background In a Phase 3 prevention trial, the monoclonal antibody combination casirivimab and imdevimab (REGEN-COVTM) administered subcutaneously (SC) prevented symptomatic SARS-CoV-2 infection in asymptomatic adults/adolescents living in the same household as a SARS-CoV-2-infected individual (index case). Individuals with cardiovascular disease (CVD) and/or diabetes are at increased risk of moderate/severe COVID-19. Methods Uninfected individuals ≥12 years, identified ≤96 hours of index case being diagnosed SARS-CoV-2 positive, were randomized 1:1 to REGEN-COV 1200mg SC or placebo. The primary endpoint was the proportion of participants who developed symptomatic infection (COVID-19) during the 28-day efficacy assessment period among those who were SARS-CoV-2 RT-qPCR negative and without evidence of immunity (seronegative) at baseline. A post-hoc analysis assessed efficacy in participants with CVD (including hypertension) and/or diabetes. Overall safety is reported. Results The study included SARS-CoV-2 RT-qPCR negative participants at baseline (n=2067). There was an 81.4% relative risk reduction (RRR) of symptomatic infection with REGEN-COV in the overall seronegative population (n=1505; Figure 1; Table 1). In participants with CVD (n=332) or diabetes (n=103), the RRRs of developing symptomatic infection with REGEN-COV versus placebo were 54.9% and 69.0%, respectively. Similar results were observed when analyses were performed regardless of baseline serology status. Treatment-emergent adverse events occurring at ≥2% included COVID-19, asymptomatic COVID-19, headache, and injection-site reaction (Table 2). Conclusions In study participants with CVD and/or diabetes, who are known to be at increased risk of severe disease if infected, treatment with REGEN-COV SC reduced the risk of developing symptomatic SARS-CoV-2 infection, consistent with the overall study results..

Background In US states, childhood immunization mandates are enforced for school registration by front-line school staff, usually secretaries. Despite substantial changes to mandate policies in several states and many countries, little attention has been paid to the people who enforce them. This qualitative pilot study aimed to uncover beliefs, attitudes, and practices regarding immunization governance of Michigan school staff. Method Front-line administrative workers from Michigan schools and district offices were solicited by email. Sixteen were interviewed remotely. Results Front-line school staff believed in vaccines, but did not advocate for vaccination while registering children. Instead, they sought low-friction bureaucratic transactions, privileging the collection of data over the promotion of public health goals. This revealed a mismatch between the goals of the front-line staff who enforce vaccine mandates in schools and the goals of the policymakers who created school vaccine mandates. Conclusions This study found low mobilization of front-line enforcers of mandates in public-facing school administration roles, a problem likely to afflict the majority of American states with the ‘mandates + exemptions’ model of immunization governance. Schools would have stronger incentives to promote vaccination if state funding were better tied to immunization compliance. Front-line staff could better enforce vaccine mandates if they were provided with resources and training about vaccine promotion.

BACKGROUND: Controversy exists regarding the optimal antibiotic regimen for use in hospitalized children with staphylococcal scalded skin syndrome (SSSS). Various regimens may confer toxin suppression and/or additional coverage for methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S aureus (MRSA). OBJECTIVES: To describe antibiotic regimens in hospitalized children with SSSS and examine the association between antistaphylococcal antibiotic regimens and patient outcomes. DESIGN/METHODS: Retrospective cohort study of children hospitalized with SSSS using the Pediatric Health Information System database (2011-2016). Children who received clindamycin monotherapy, clindamycin plus MSSA coverage (eg, nafcillin), or clindamycin plus MRSA coverage (eg, vancomycin) were included. The primary outcome was hospital length of stay (LOS); secondary outcomes were treatment failure and cost. Generalized linear mixed-effects models were used to compare outcomes among antibiotic groups. RESULTS: Of 1,259 children included, 828 children received the most common antistaphylococcal antibiotic regimens: clindamycin monotherapy (47%), clindamycin plus MSSA coverage (33%), and clindamycin plus MRSA coverage (20%). Children receiving clindamycin plus MRSA coverage had higher illness severity (44%) compared with clindamycin monotherapy (28%) and clindamycin plus MSSA (32%) (P = .001). In adjusted analyses, LOS and treatment failure did not differ among the three regimens (P = .42 and P = .26, respectively). Cost was significantly lower for children receiving clindamycin monotherapy and highest in those receiving clindamycin plus MRSA coverage (mean, $4,839 vs $5,348, respectively; P < .001). CONCLUSIONS: In children with SSSS, the addition of MSSA or MRSA coverage to clindamycin monotherapy was associated with increased cost and no incremental difference in clinical outcomes.

Background The goal of our investigation was to describe the incidence of serious bacterial infection (SBI, defined as bacteremia, urinary tract infection (UTI), or meningitis) in young infants with and without documented viral pathogens. Methods This was a retrospective cross-sectional study (1/2016–12/2017) in 3 emergency departments (EDs). Previously healthy 0–60-day-old infants were included if at least respiratory viral testing and a blood culture was obtained. The frequency of SBI, the primary outcome, was compared among infants with/without respiratory viral infections using the Pearson Chi-square test (or Fisher's Exact Test) and unadjusted odds ratios (OR). Results The median age of the 597-infant cohort was 32 days (interquartile range: 20–45 days); 42% were female. Eighty-three percent were well appearing in the ED and 72% were admitted. ED triage vitals commonly revealed tachypnea (68%), pyrexia (45%), and tachycardia (28%); hypoxemia (5%) was uncommon. Twenty-eight percent had positive viral testing, most commonly RSV (93/169, 55%), parainfluenza (29, 17%), and influenza A (23, 14%). Eighty-three infants (13.9%) had SBI: 8.4% (n = 50) had UTI alone, 2.8% (n = 17) had bacteremia alone, 1.2% (n = 7) had bacteremia + UTI, 1.0% (n = 6) had bacteremia + meningitis, and 0.5% (n = 3) had meningitis alone. Infants with documented respiratory viral pathogens were less likely to have any SBI (OR: 0.23; 95% CI: 0.11–0.50), UTI (OR 0.22, 95% CI: 0.09–0.56), or bacteremia (OR 0.27, 95% CI: 0.08–0.9) than infants with negative viral testing. There was no difference in meningitis frequency based on viral status (OR: 0.13, 95% CI: 0.008–2.25). Conclusions The frequency of bacteremia and UTI was lower in young infants with respiratory viral infections compared to infants with negative respiratory viral testing.

Background: Urinary tract infections (UTIs) are the most common serious bacterial infection in young febrile infants, and the urinalysis (UA) is an accurate screening test for emergency department (ED) evaluation. Precise estimates of risk of concomitant bacteremia and/or bacterial meningitis (invasive bacterial infections; IBI) in febrile infants ≤ 60 days have been based on presence of UTIs rather than positive UAs, and lack large prospective study. Objective: We sought to determine the prevalence of IBIs in febrile infants 0-28 …