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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 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.

The Flaviviridae family comprises important human pathogens, including Dengue, Zika, West Nile, Yellow Fever and Japanese Encephalitis viruses. The viral genome, a positive-sense single-stranded RNA, is packaged by a single protein, the capsid protein, which is a small and highly basic protein that form intertwined homodimers in solution. Atomic-resolution structures of four flaviviruses capsid proteins were solved either in solution by nuclear magnetic resonance spectroscopy, or after protein crystallization by X-ray diffraction. Analyses of these structures revealed very particular properties, namely (i) the predominance of quaternary contacts maintaining the structure; (ii) a highly electropositive surface throughout the protein; and (iii) a flexible helix (α1). The goal of this review is to discuss the role of these features in protein structure-function relationship.

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.]

Neuroinflammation and dysfunction of the blood–brain barrier (BBB) are two prominent mechanisms of secondary injury in neurotrauma. It has been suggested that Toll-like receptors (TLRs) play important roles in initiating and propagating neuroinflammation resulting from traumatic brain injury (TBI), but potential beneficial effects of targeting these receptors in TBI have not been broadly studied. Here, we investigated the effect of targeting TLRs with proteoglycan 4 (PRG4) on post-traumatic neuroinflammation and BBB function. PRG4 is a mucinous glycoprotein with strong anti-inflammatory properties, exerting its biological effects by interfering with TLR2/4 signaling. In addition, PRG4 has the ability to inhibit activation of cluster of differentiation 44 (CD44), a cell-surface glycoprotein playing an important role in inflammation. Using the controlled cortical impact model of TBI in rats, we showed a rapid and prolonged upregulation of message for TLR2/4 and CD44 in the injured cortex. In the in vitro model of the BBB, recombinant human PRG4 (rhPRG4) crossed the endothelial monolayers through a high-capacity, saturable transport system. In rats sustaining TBI, PRG4 delivery to the brain was enhanced by post-traumatic increase in BBB permeability. rhPRG4 injected intravenously at 1 h post-TBI potently inhibited post-traumatic activation of nuclear factor kappa B and extracellular signal-regulated kinases 1/2, the two major signal transduction pathways associated with TLR2/4 and CD44, and curtailed the post-traumatic influx of monocytes. In addition, PRG4 restored normal BBB function after TBI by preventing the post-traumatic loss of tight junction protein claudin 5 and reduced neuronal death. Our observations provide support for therapeutic strategies targeting TLRs in TBI.

Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain’s ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OX2R) have shown promise as novel therapeutics that directly target the pathophysiology of the disease. However, identification of drug-like OX2R agonists has proven difficult. Here we report cryo-electron microscopy structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist. The extended carboxy-terminal segment of the peptide reaches into the core of OX2R to stabilize an active conformation, while the small-molecule agonist binds deep inside the orthosteric pocket, making similar key interactions. Comparison with antagonist-bound OX2R suggests a molecular mechanism that rationalizes both receptor activation and inhibition. Our results enable structure-based discovery of therapeutic orexin agonists for the treatment of NT1 and other hypersomnia disorders., Agonists of the orexin receptor 2 (OX2R) show promise in the treatment of narcolepsy. Cryo-EM structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist suggest a molecular mechanism that rationalizes both receptor activation and inhibition.

BACKGROUND Extensive literature assesses risky adolescent driving, but nothing examines what makes teens avoid driving. Many assume teenagers are eager to drive, but evidence suggests internalizing symptoms lead some to avoid driving. AIMS This study tested whether depressive and anxious symptomology predicted longitudinal driving avoidance in novice teen drivers. MATERIALS AND METHODS N = 56 16-year-olds (52% female; 48% Black/African American) completed three observations over 6 months. At Time 1, participants reported depressive (Center for Epidemiological Studies Depression 10-item Scale) and anxious (Generalized Anxiety Disorder 7-item Scale) symptomologies, and driving avoidance (Driving Habits Questionnaire [DHQ]), repeating DHQ at Times 2 and 3. Multiple linear regression tested whether symptomologies predicted avoidance at licensure. Linear mixed models tested associations between symptomologies and avoidance over time. RESULTS High anxiety predicted greater avoidance at baseline and over 6 months. Depressive symptoms did not predict avoidance. DISCUSSION Findings warrant an assessment of anxious adolescents' barriers to driving and avoidance impacts on crash risk.

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.

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.

Post-thrombotic syndrome (PTS) is an end stage manifestation of deep vein thrombosis. This is an inherently inflammatory process, with consequent fibrosis. Multiple cellular types are involved, and are likely driven by leukocytes. Herein, we review the current gaps in therapy, and insights from rodent models of venous thrombosis that suggest possible targets to treat and prevent PTS.

In a New Zealand population-based case-control study we assessed associations with occupational exposure to electric shocks, extremely low-frequency magnetic fields (ELF-MF) and motor neurone disease using job-exposure matrices to assess exposure. Participants were recruited between 2013 and 2016. Associations with ever/never, duration, and cumulative exposure were assessed using logistic regression adjusted for age, sex, ethnicity, socioeconomic status, education, smoking, alcohol consumption, sports, head or spine injury, and solvents, and was mutually adjusted for the other exposure. All analyses were repeated stratified by sex. An elevated risk was observed for having ever worked in a job with potential for electric shocks (odds ratio (OR) = 1.35, 95% confidence interval (CI): 0.98, 1.86), with the strongest association for the highest level of exposure (OR = 2.01, 95% CI: 1.31, 3.09). Analysis by duration suggested a nonlinear association: Risk was increased for both short duration (24 years; OR = 1.88; 95% CI: 1.05, 3.36) in a job with high level of electric shock exposure, with less pronounced associations for intermediate durations. No association with ELF-MF was found. Our findings provide support for an association between occupational exposure to electric shocks and motor neurone disease but did not show associations with exposure to work-related ELF-MF.

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

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.

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.

Micromechanical characterization by nanoindentation of PDMS substrates for cardiac mechanobiology studies.

Dengue virus (DENV) is the most widespread arbovirus, responsible for a wide range of clinical manifestations, varying from self-limited illness to severe hemorrhagic fever. Dengue severity is associated with host intense proinflammatory response and monocytes have been considered one of the key cell types involved in the early steps of DENV infection and immunopathogenesis. To better understand cellular mechanisms involved in monocyte infection by DENV, we analyzed the expression levels of 754 human microRNAs in DENV-infected THP-1 cells, a human monocytic cell line. Eleven human microRNAs showed differential expression after DENV infection and gene ontology and enrichment analysis revealed biological processes potentially affected by these molecules. Five downregulated microRNAs were significantly linked to cellular response to stress, four to cell death/apoptosis, two to innate immune responses and one upregulated to vesicle mediated, TGF-β signaling, phosphatidylinositol mediated signaling, lipid metabolism process and blood coagulation.

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.

Venous thromboembolism (VTE) is a significant cause of mortality1, yet its genetic determinants remain incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank testing ~13 million DNA sequence variants for association with VTE (26,066 cases; 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 VTE cases and 167,295 controls. We identified 22 novel loci, bringing the total number of VTE-associated loci to 33 and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for VTE that identifies 5% of the population at equivalent incident VTE risk to carriers of the established F5 Leiden (p.R506Q) and prothrombin G20210A mutations. Our data provide new mechanistic insights into the genetic epidemiology of VTE and suggest a greater overlap among venous and arterial cardiovascular disease than previously suggested., Editorial summary Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

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.

Purpose: Immune checkpoint inhibitors (ICI) targeting PD1, PDL1, or CTLA4 are associated with immune-related adverse events (irAE) in multiple organ systems including myocarditis. The pathogenesis and early diagnostic markers for ICI-induced myocarditis are poorly understood, and there is currently a lack of laboratory animal model to enhance our understanding. We aimed to develop such a model using cynomolgus monkeys. Experimental Design: Chinese-origin cynomolgus monkeys were dosed intravenously with vehicle or nivolumab 20 mg/kg plus ipilimumab 15 mg/kg once weekly and euthanized on day 29. Results: Multiple organ toxicities were observed in cynomolgus monkeys, and were characterized by loose feces, lymphadenopathy, and mononuclear cell infiltrations of varying severity in heart, colon, kidneys, liver, salivary glands, and endocrine organs. Increased proliferation of CD4+ and CD8+ T lymphocytes as well as an increase in activated T cells and central memory T cells in the blood, spleen, and lymph nodes, were observed. Transcriptomic analysis suggested increased migration and activation of T cells and increased phagocytosis and antigen presentation in the heart. Mononuclear cell infiltration in myocardium was comprised primarily of T cells, with lower numbers of macrophages and occasional B cells, and was associated with minimal cardiomyocyte degeneration as well as increases in cardiac troponin-I and NT-pro-BNP. Morphologically, cardiac lesions in our monkey model are similar to the reported ICI myocarditis in humans. Conclusions: We have developed a monkey model characterized by multiple organ toxicities including myocarditis. This model may provide insight into the immune mechanisms and facilitate biomarker identification for ICI-associated irAEs.

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

OBJECTIVE: Examine cross-sectional associations between body mass index (BMI) and related health behaviors, barriers and facilitators to health care, and perceived health status among a sample of U.S. Marshallese adults with Type 2 diabetes and evaluate associations of interest between participants and their family members. DESIGN: Cross-sectional baseline data were analyzed from participants in a diabetes self-management education intervention trial. SETTING: Data collection took place in home or community settings through a community-academic partnership in Arkansas. PARTICIPANTS: Study participants consisted of U.S. Marshallese adults with Type 2 diabetes (N=221) and their family members (N=211) recruited through community settings. INTERVENTION(S): N/A MAIN OUTCOME MEASURE(S): Participants’ height and weight were measured using standard protocols to calculate BMI (kg/m(2)). Diet, physical activity, health care access, financial strain related to health care, perceived health status, and health care satisfaction were measured using self-report surveys. RESULTS: Participants’ mean BMI was 31.0 (95% CI: 30.2–31.7), with over half of study participants and their family members’ BMI falling in the obese category. Participants’ BMI was positively associated with spreading health care bill payments over time (β=1.75 (SE=0.87); p=0.045). Positive associations between participants and their family members were observed for self-reported health status conditions, health care coverage, health care utilization, and health care satisfaction. CONCLUSION: Study findings highlight the high prevalence of obesity and related risk factors among U.S. Marshallese adults with Type 2 diabetes and emphasize the need for intervention strategies that build upon cultural strengths and target community, policy, systems, and environmental changes to address obesity and chronic disease in this marginalized community.

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

Significance The COVID-19 pandemic has disproportionately affected patients with comorbidities, namely, obesity and type 2 diabetes. Macrophages (Mφs) are a key innate immune cell primarily responsible for the harmful, hyperinflammatory “cytokine storm” in patients that develop severe COVID-19. We describe a mechanism for this Mφ-mediated cytokine storm in response to coronavirus. In response to coronavirus infection, expression of the chromatin-modifying enzyme, SETDB2, decreases in Mφs, leading to increased transcription of inflammatory cytokines. Further, we find SETDB2 is regulated by an interferon beta (IFNβ)/JaK/STAT3 mechanism, and that exogenous administration of IFNβ can reverse inflammation, particularly in diabetic Mφs via an increase in SETDB2. Together, these results suggest therapeutic targeting of the IFNβ/SETDB2 axis in diabetic patients with COVID-19 may decrease pathologic inflammation., COVID-19 induces a robust, extended inflammatory “cytokine storm” that contributes to an increased morbidity and mortality, particularly in patients with type 2 diabetes (T2D). Macrophages are a key innate immune cell population responsible for the cytokine storm that has been shown, in T2D, to promote excess inflammation in response to infection. Using peripheral monocytes and sera from human patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a murine hepatitis coronavirus (MHV-A59) (an established murine model of SARS), we identified that coronavirus induces an increased Mφ-mediated inflammatory response due to a coronavirus-induced decrease in the histone methyltransferase, SETDB2. This decrease in SETDB2 upon coronavirus infection results in a decrease of the repressive trimethylation of histone 3 lysine 9 (H3K9me3) at NFkB binding sites on inflammatory gene promoters, effectively increasing inflammation. Mφs isolated from mice with a myeloid-specific deletion of SETDB2 displayed increased pathologic inflammation following coronavirus infection. Further, IFNβ directly regulates SETDB2 in Mφs via JaK1/STAT3 signaling, as blockade of this pathway altered SETDB2 and the inflammatory response to coronavirus infection. Importantly, we also found that loss of SETDB2 mediates an increased inflammatory response in diabetic Mϕs in response to coronavirus infection. Treatment of coronavirus-infected diabetic Mφs with IFNβ reversed the inflammatory cytokine production via up-regulation of SETDB2/H3K9me3 on inflammatory gene promoters. Together, these results describe a potential mechanism for the increased Mφ-mediated cytokine storm in patients with T2D in response to COVID-19 and suggest that therapeutic targeting of the IFNβ/SETDB2 axis in T2D patients may decrease pathologic inflammation associated with COVID-19.

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 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 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..

A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.

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 …

IMPORTANCE: Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. OBJECTIVE: To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. MAIN OUTCOMES AND MEASURES: Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. RESULTS: Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). CONCLUSIONS AND RELEVANCE: NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.

Objectives To explore the predictive ability of capillary blood gas (CBG) pCO2 for respiratory decompensation in infants aged ≤6 months with bronchiolitis admitted from the emergency department; to determine whether end-tidal CO2 (etCO2) capnography can serve as a less invasive substitute for CBG pCO2. Study design This was a prospective cohort study of previously healthy infants aged ≤6 months admitted for bronchiolitis from the emergency department (ED). Initial CBG pCO2 and etCO2 capnography were obtained in the ED prior to inpatient admission. Simple logistic regression modeling was used to examine the associations of CBG pCO2 and etCO2 capnography with respiratory decompensation. Pearson's correlation measured the relationship between CBG pCO2 and etCO2 capnography. Results Of 134 patients, 61 had respiratory decompensation. There was a significant association between CBG pCO2 and respiratory decompensation (OR = 1.07, p = 0.003), even after outlying values were excluded (OR = 1.06, p = 0.005). End tidal CO2 capnography was not significantly associated with decompensation (OR = 1.02, p = 0.17), even after outlying values were excluded (OR = 1.02, p = 0.24). There was a moderate correlation between etCO2 capnography and CBG pCO2 (r = 0.39, p Conclusion In infants with bronchiolitis, CBG pCO2 provides an objective measure for predicting respiratory decompensation, and a single etCO2 measurement should not replace its use.

Objective Chronic venous disease (CVD) describes a spectrum of conditions associated with venous hypertension. The association between various CVD etiologies and the subsequent risk of venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary embolism, is a topic of considerable clinical interest. The aims of the present review were to characterize the risk of VTE according to the CVD etiology and to determine the optimal anticoagulation strategy for the treatment or prevention of VTE in patients with CVD. Methods An extensive search of the available surgical and medical data was conducted in PubMed and Google Scholar. We searched for the following terms and other related terms to identify relevant studies: CVD, chronic venous insufficiency, varicose veins, post-thrombotic syndrome (PTS), anticoagulation, venous thromboembolism, and venous disease scoring systems (eg, CEAP [clinical, etiology, anatomic, pathophysiology], Villalta, Ginsberg, venous clinical severity score). The identified studies included randomized control trials, retrospective and prospective observational studies, narrative and systematic reviews, case reports, and case series that contributed to the proposed aims. The ClinicalTrials.gov database was also queried to identify any relevant ongoing clinical trials. Results Congenital CVD carries a heightened risk of VTE, although few higher level studies are available to inform on this topic or on the appropriate anticoagulation strategies for these patients. Noncongenital CVD seems to carry a heightened risk of VTE, although few studies have adequately differentiated between primary and secondary etiologies. Varicose veins are a risk factor for primary VTE but might not be associated with an increased risk of recurrent VTE. In the hospital setting, patients with varicosities should be provided thromboprophylaxis. In the setting of varicose vein intervention, high-risk patients should be identified using risk assessment models and receive thromboprophylaxis. The risk of recurrent VTE in the setting of PTS is unclear but indefinite anticoagulation is not currently indicated. For patients with PTS, residual vein thrombosis might be an indicator of when anticoagulation can be safely stopped, although practical limitations to its application exist. Conclusions CVD is associated with an increased risk of VTE. Few studies have differentiated between classes of CVD using a standardized method and have assessed the efficacy of anticoagulation prophylaxis against or treatment of VTE. Additional studies are needed to determine the optimal therapy for preventing and treating VTE in patients with active concurrent CVD.

Objectives: This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods: We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case–control study, conducted in six European countries in 1998–2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results: We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01–4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00–4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95–4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions: Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.

In humans, blood glucose is the main reporter of fed and fasting states. Its concentration directly regulates the secretion of hormones, including glucagon and insulin by the pancreas and glucocorticoids by the adrenal cortex. These hormones, in a coordinated action, regulate the energy metabolism in different organs, allowing the blood concentration of glucose to be maintained within a narrow range by a precise system balancing glucose production by the liver and its utilization by peripheral tissues.

The survival of our ancestors was highly dependent on hunting, gathering”: and fighting, behaviors that demanded intense physical activity. A sedentary lifestyle in that environment would certainly result in the elimination of the individuals. This situation imposed a selective pressure directed to adaptations of human physiology to a high capacity of physical activity, resulting in the development of a very efficient locomotor system, in which the skeletal muscles correspond to about 40 % of the body mass and account for a great proportion of the average energy consumption of the organism. The present-day sedentarism is dissonant with the human genetic background selected to favor a physically active lifestyle and probably consists in one of the main causes of the increasing incidence of modern chronic diseases, such as hypertension, obesity, and insulin resistance.