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We conducted a nested case-control study utilizing cases of clinical pneumonia identified in a community-based prospective surveillance study of children under 3 years of age in order to test the validity of a survey questionnaire. Three types of sex- and age-matched concurrent controls were selected from the surveillance population: acute respiratory infection (ARI) clinic controls. ARI community controls and healthy community controls. Survey interviews were scheduled at random for any of four consecutive 7-day periods after the diagnosis of the case. The questionnaire covered a 30-day recall period. The combination of cough with fast breathing or shortness of breath, and with fever, provided the highest positive predictive value for pneumonia. The sensitivity of some questions dropped when the interview took place more than 15 days after the diagnosis of the case. However, the utilization of a 15-day recall period did not increase the positive predictive value of the survey. We conclude that in this trained population under surveillance, a survey questionnaire utilizing a 30-day recall period and using the combination of cough, fast breathing or shortness of breath and fever to define episodes with a high likelihood of pneumonia, offers an acceptable tool for the monitoring and evaluation of respiratory control programmes. This questionnaire needs further evaluation in an untrained population and in other regions before it can be adopted for use in ARI control programmes. [ABSTRACT FROM AUTHOR]

Purpose: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases., Methods: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6 KozakGAL4 allele to assess the expression pattern of dYkt6., Results: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, developmental delay, and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual is homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] and exhibited neurodevelopmental disorders and optic atrophy. Fly dYkt6 is essential and is expressed in the fat body (analogous to liver) and central nervous system. Wild-type genomic rescue constructs can rescue the lethality and autophagic flux defects, whereas the variants are less efficient in rescuing the phenotypes., Conclusion: The YKT6 variants are partial loss-of-function alleles, and the p.(Tyr185Cys) is more severe than p.(Tyr64Cys)., Competing Interests: Conflict of Interest BCM and Miraca Holdings have formed a joint venture with shared ownership and governance of BG, which performs clinical microarray analysis, clinical ES (cES), and clinical biochemical studies. James R. Lupski serves on the Scientific Advisory Board of the BG. James R. Lupski has stock ownership in 23andMe, is a paid consultant for Genomics International, and is a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, genomic disorders, and bacterial genomic fingerprinting. Nhu Thao Nguyen Galván serves as a consultant for 3DSystems. Davut Pehlivan provides consulting service for Ionis Pharmaceuticals. Wendy K. Chung is on the Board of Directors of Prime Medicine and Rallybio. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing conducted at Baylor Genetics Laboratories. All other authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: The use of sports supplements (SS) to improve sports performance is widespread in all types of athletes, however, the specific characteristics of mountain races may require the use of certain SS. Despite being a sport where the consumption of SS seems widespread, few studies have been conducted in this regard. The objective of this study is to analyze the pattern of SS consumption of mountain runners in relation to the degree of scientific evidence, sex, and level of competition., Methods: Descriptive and cross-sectional study on the consumption and habitual use of SS of 357 federated mountain runners in Spain. Data were collected through a validated questionnaire., Results: From the total sample, 93.84% of the athletes stated that they consumed SS, with no differences observed based on the competitive level or in terms of sex; however, there were significant differences according to the competitive level in terms of the number of SS consumed, with consumption being greater at a higher competitive level ( p = 0.009). The most consumed SS were sports bars (66.1%), sports drinks (60.5%), sports gels (52.9%), and caffeine (46.2%)., Conclusions: The consumption of SS in mountain races is high, and the number of SS consumed is higher as the competition level increases. The four SS most consumed by the participants in this study were all included in category A in the classification of the Australian Institute of Sport (AIS), this category is the one with the greatest scientific evidence.

Objective: The coronavirus disease 2019 (COVID-19) pandemic dramatically accelerated a growing trend toward online and asynchronous education and professional training, including in the disaster medicine and public health sector. This study analyzed the impact of the COVID-19 pandemic on the growth of the TRAIN Learning Network (TRAIN) for the year 2020 and evaluated pandemic-related changes in use patterns by disaster and public health professionals., Methods: The TRAIN database was queried to determine the change in the number of registered users, total courses completed, and courses completed related to COVID-19 during 2020., Results: In 2020, a total of 755,222 new users joined the platform - nearly 3 times the average added annually over the preceding 5 y (2015-2019). TRAIN users completed 3,259,074 training courses in 2020, more than double the average number of training courses that were completed annually from 2015-2019. In addition, 17.8% of all newly added disaster and public health training courses in 2020 were specifically related to COVID-19., Conclusion: Online education provided by TRAIN is a critical tool for just-in-time disaster health training following a disaster event or public health emergency, including in a global health crisis such as a pandemic.

Abstract: A scoping review was conducted to describe the history of the National Disaster Medical System (NDMS) in the context of US military medical preparedness for a large-scale overseas military conflict. National Disaster Medical System civilian hospitals would serve as backups to military treatment facilities if both US Department of Defense and US Department of Veterans Affairs hospitals reached capacity during such a conflict. Systematic searches were used to identify published works discussing the NDMS in the scientific and gray literature. Results were limited to publicly available unclassified English language works from 1978 to January 2022; no other restrictions were placed on the types of published works. Full-text reviews were conducted on identified works (except student papers and dissertations) to determine the extent to which they addressed NDMS definitive care. Data charting was performed on a final set of papers to assess how these works addressed NDMS definitive care. The search identified 54 works published between 1984 and 2022. More than half of the publications were simple descriptions of the NDMS (n = 30 [56%]), and most were published in academic or professional journals (n = 38 [70%]). Only nine constituted original research. There were recurrent criticisms of and recommendations for improving the definitive care component of the NDMS. The lack of published literature on NDMS definitive care supports the assertion that the present-day NDMS may lack the capacity and military-civilian interoperability necessary to manage the casualties resulting from a large-scale overseas military conflict., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Our purpose is to describe the structure, function and outcomes of our multidisciplinary pediatric thyroid program and to evaluate our experience in comparison to other high-volume centers., Methods: We reviewed all thyroid operations performed 10/2012 through 09/2019, and examined number of cases per year, patient demographics, procedures, final diagnoses and results. Primary outcomes were hypoparathyroidism and recurrent laryngeal nerve (RLN) injury at 12 months. Data were analyzed using descriptive statistics and univariate analyses., Results: We performed 294 thyroid operations on 279 patients. Seventy-nine percent were female. Median age was 15 years (IQR: 12-17). Operations included total thyroidectomy (65%), lobectomy (30%) and completion thyroidectomy (5%). Most common diagnoses were Graves' disease (35%), malignancy (29%), and benign nodule (20%). We developed an evidence-based clinical pathway and conducted weekly multidisciplinary meetings. A clinical data specialist reviewed process and outcome measures routinely. Overall, 6 patients (2.0%) had hypoparathyroidism and 2 (0.7%) had unilateral RLN injury at 12 months. Two of the patients with clinical suspicion of permanent hypoparathyroidism were ultimately weaned off calcium. Both patients with RLN injury had extensive locally advanced malignant disease involving the nerve., Conclusions: Our multidisciplinary team achieved excellent long-term outcomes for pediatric thyroid surgery comparable to other high-volume pediatric and adult centers., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Study of liver explants of biliary atresia (BA) patients with successful Kasai portoenterostomy (KP)., Methods: Pathology and medical records of BA liver explants from January 2009 to June 2018 with successful KP were reviewed along with appropriate controls., Results: Fourteen out of 68 (20.6%) BA patients with LT had a successful KP. Median age at BA diagnosis, KP and LT was 60.5 days, 61 days, and 10 years, respectively, with conjugated bilirubin (c-bil) normalizing at 12.5 weeks after KP. Advanced fibrosis was diffuse in 2/14 (14.3%) explants, limited to periphery in 11/14 (78.6%) and absent in 1. Hilar partial nodular transformation (PNT) was seen in 11 explants (78.6%) and diffuse nodular regenerative hyperplasia (NRH) in 2 (14.3%). Areas of PNT and NRH showed diffuse portal sclerosis (100%), complete and incomplete portal vein (PV) stenosis (100%), PV herniation (100%), hypervascular portal tracts (20%), periportal abnormal vessels (100%), abundant lymphatic collaterals (100%), mild medial hepatic arterial hypertrophy (100%), and delicate fibrous septae (100%). Extrahepatic PVs showed variable luminal occlusion with mean PV intima to full thickness ratio of 0.6 +/- 0.11; significantly higher than age-matched noncirrhotic (n = 27, 0.08 +/- 0.09; P < 0.0001) and cirrhotic controls (n = 19, 0.34 +/- 0.2; P = 0.0015); and comparable to BA patients with failed KP (P = 0.82) and without KP (P = 0.04)., Conclusions: BA patients with successful KP can present with obliterative portal venopathy (OPV). In the context of optimal bile drainage, portal hypertension may not be because of advanced parenchymal fibrosis but possibly because of OPV. Vascular abnormalities of the PV system should be investigated in BA patients.

Intratubular germ cell neoplasia (ITGCN) of the testis is a precursor to testicular germ cell tumor (TGCT), which can lead to the development of invasive cancer. In patients with a history of previously treated unilateral TGCT, treatment for ITGCN of the contralateral testis needs to be balanced with the risks of subsequent infertility. Here, we present a 17- year- old patient with ITGCN diagnosed after treatment of contralateral nonseminomatous TGCT who was successfully treated with a partial orchiectomy followed by low-dose radiation with preservation of his testosterone production., (© 2019 Wiley Periodicals, Inc.)

Cystic fibrosis liver disease (CFLD) has long been postulated to be secondary to dysfunctional cystic fibrosis transmembrane conductance regulator in the apical biliary epithelium, leading to bile stasis and eventually cirrhosis with portal hypertension. However, pathologic changes in the cystic fibrosis (CF) liver are distinct from the pancreas and lungs in that fibrocystic changes are absent. 1,2 Furthermore, the lack of clinically evident biliary obstruction and liver dysfunction suggest there may be alternative mechanisms that contribute to CFLD. Two recent studies in young adults described obliterative portal venopathy (OPV) and noncirrhotic portal hypertension (NCPH) as the predominant pathophysiology in young adults (median, 22 y) with CFLD. 3,4 It is unknown if OPV develops early in childhood. Herein, we report the clinical features and liver pathology in 17 explants from children and adolescents with CF, representing 13.6% (17 of 125) of the CF liver transplant population in the United States according to the United Network for Organ Sharing and Organ Procurement and Transplantation Network., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In the fall of 2017, Hurricane Harvey, one of the most costly hurricanes in American history, ravaged the Texas Gulf Coast, interrupting basic sanitation systems to hundreds of thousands of Texas residents. In the aftermath of Hurricane Harvey, our Houston hospitals noted an uptick in the incidence of cases of mucormycosis. Among the most vulnerable and affected have been immunocompromised transplant recipients. Here, we describe the successful management of 2 patients with atypical presentations of mucormycosis, 2 cutaneous infections after liver transplantation. Our comprehensive treatment strategy based upon guidelines and experience included coordinating aggressive surgical and medical therapies. We discuss our approach to surgical management including the extent and frequency of debridement, the methods of assessing disease-free margins, and minimizing the morbidity of radical debridement with temporary coverage and forethought to long-term reconstruction. Additionally, we describe the concurrent medical management, including type, route, and duration of antifungal therapy, minimizing suppression of the innate immune system, and optimizing the wound healing environment through maintaining nutritional status.

We retrospectively studied the clinical and histologic features of pediatric fundic gland polyps (FGPs) in 16 patients. FGPs had an endoscopic prevalence of 0.25% in 8527 pediatric gastric biopsies. Five patients had familial adenomatous polyposis (FAP). The median age of onset was 17.7 years in FAP and 17.3 years in sporadic patients. All syndromic patients were asymptomatic and FGPs were identified during surveillance for existing or concurrent colon polyps. They did not take antacids. In comparison, all 11 sporadic FGPs were identified during evaluation of symptomatic patients who had taken antacids (median duration 21 months). Syndromic FGPs can be multiple at single endoscopy and were more likely to recur, while sporadic FGPs were often single. None of the sporadic patients had recurrence of FGPs or a subsequent diagnosis of FAP during a median follow-up of 20.5 months. The dilated fundic glands were lined by parietal and chief cells only in a majority (22/41, 53.7%) of syndromic FGPs, while additional tall mucinous lining cells were found in all sporadic FGPs. Syndromic FGPs did not have parietal cell hypertrophy in the background oxyntic mucosa. Nuclear immunopositivity for beta-catenin was essentially absent in all the FGPs. In conclusion, FGPs were rare in pediatric patients. In syndromic patients, FGPs are asymptomatic and did not precede colon polyps. Prolonged antacid intake seems to be associated with development of sporadic FGPs. Cellular components of dilated fundic glands and background parietal cell hypertrophy can be useful features to eliminate concern for syndromic polyposis.

Background Aims: Esophageal eosinophilia (EE) can be caused by gastroesophageal reflux disease (GERD), proton-pump inhibitor-responsive EE (PPI-REE) or eosinophilic esophagitis (EoE). This study quantified protein expression and S-nitrosylation (SNO) post-translational modifications in EE to elucidate potential disease biomarkers., Methods: Proximal and distal esophageal (DE) biopsy proteins in patients with EE and in controls were assayed for protein content and fluorescence-labeled with and without ascorbate treatment. Protein SNO was determined, and selected protein spots were identified by matrix-assisted laser desorption ionization time-of-flight/mass spectrometry. Western blot and ingenuity pathway analysis were performed., Results: Ninety-one of 648 proteins showed differential expression. There were significantly altered levels of abundance for 11 proximal and 14 DE proteins. Hierarchal clustering revealed differential SNO in inflamed tissues, indicating reactive nitrogen/oxygen species involvement. Galectin-3 was upregulated in both proximal (p < 0.04) and distal (p < 0.004) esophageal EE biopsies compared to controls. In distal EE samples, galectin-3 was significantly S-nitrosylated (p < 0.004). Principal component analysis revealed sample group discrimination distally., Conclusion: Proteomic analysis in EE esophageal mucosa revealed a distinct abundance and nitrosylation profile, most prominently in distal biopsies. Galectin-3 was upregulated in expression and SNO, which may indicate its potential role in mucosal inflammation. These results call for more studies to be performed to investigate the role of galectin-3 in GERD, PPI-REE and EoE., (© 2016 S. Karger AG, Basel.)

Background: To evaluate the use of surveillance cultures (SCs) to prevent catheter-related bloodstream infections (CRBSIs) in asymptomatic hemodialysis (HD) patients., Methods: In 2011-2012, we conducted a prospective study of HD patients with tunneled cuffed central venous catheters (TCCs). Colonization of the catheter lumen was assessed every 15 days by inoculating ~5 mL endoluminal blood into aerobic culture bottles. Individual patients were triaged based on SC results: group 1 (negative); group 2 (coagulase-negative Staphylococcus [CoNS] with time-to-positivity (TTP) >14 hours); group 3 (CoNS with TTP ≤14 hours); and group 4 (any microorganism other than CoNS and any TTP)., Results: We studied 104 patients (129 TCCs). Median follow-up was 262.5 days (interquartile range [IR], 135.0-365.0). A total of 1,734 SCs were collected (median, 18 per patient; IR, 10.0-24.0), of which 1,634 (94.2%) were negative (group 1) and 100 (5.8%) were positive (group 2: 79; group 3: 12, group 4: 9). In groups 2 and 3, 19 TCCs required antibiotic lock therapy (ALT). In group 4, all patients received intravenous therapy and ALT. Under this protocol, there were 0.27 episodes of CRBSI per 1,000 catheter days compared with 1.65 (P < .001) prior to its implementation., Conclusion: SCs based on easily accessible samples proved useful in triaging HD patients at a high risk of infection., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Cardiac arrhythmias are a frequent event in chronic hemodialysis patients. The aim of this study was to evaluate the efficacy and safety of acetate-free hemofiltration with potassium-profiled dialysate (AFB-K) dialysis compared with constant potassium acetate-free biofiltration (AFB). Twelve patients (mean age 79 years) affected by cardiac arrhythmias or at a high risk for arrhythmia (advanced age, hypertension, left ventricular hypertrophy, heart valve disease, coronary artery disease, diabetes, paroxysmal atrial fibrillation) participated in a single-center, sequential cohort study. All were treated with hemodialysis 3 times per week, using constant potassium AFB for the first 3 weeks, followed by an AFB-K dialysate for the subsequent 3 weeks. The hemofilter, duration of dialysis, and electrolyte concentration were the same in both treatments. Both AFB-K and constant potassium AFB dialytic techniques were safe and well tolerated. The results of biochemical tests were similar, except for serum potassium levels after 2 hr of dialysis, which were significantly higher in the AFB-K group (4.0 mmol/L) than in the constant potassium AFB group (3.6 mmol/L) (p<0.001). All cardiac variables improved during AFB-K dialysis. There was a significant reduction of postdialysis QT intervals corrected for heart rate in the AFB-K group (448.8 ms) compared with the constant potassium AFB group (456.8 ms) (p=0.039). The severity and mean number of ventricular extasystoles also decreased (163.5 vs. 444.5/24 hr). Potassium profiling during hemodialysis treatment may be beneficial for patients with arrhythmias or at those risk of arrhythmias, particularly those with predialysis hyperkalemia.

Patients with xeroderma pigmentosum (XP) have defective DNA repair and a high predisposition to developing abnormalities and neoplasia in the sun-exposed areas of the skin and mucous membranes. The most common tumors reported in patients with XP are squamous cell carcinomas, basal cell carcinomas, and melanomas. Atypical fibroxanthoma (AFX) is a pleomorphic tumor that arises predominantly in the sun-damaged skin of the head and neck regions of the elderly. We describe a unique case of a 6-year-old African American boy with XP who developed an atypical fibroxanthoma and 2 squamous cell carcinomas in the conjunctiva. The clinical and histopathologic findings of AFX are discussed.

Progressive, irreversible fibrosis is one of the most clinically significant consequences of ionizing radiation on normal tissue. When applied to lungs, it leads to a complication described as idiopathic pneumonia syndrome (IPS) and eventually to organ fibrosis. For its high mortality, the condition precludes treatment with high doses of radiation. There is widespread interest to understand the pathogenetic mechanisms of IPS and to find drugs effective in the prevention of its development. This report summarizes our experience with the protective effects of L 158,809, an angiotensin II (ANG II) receptor blocker, and two angiotensin converting enzyme (ACE) inhibitors in the development of IPS and the role of transforming growth factor beta (TGF-beta) and of alpha-actomyosin (alpha SMA) in pathogenesis of radiation induced pulmonary fibrosis in an experimental model of bone marrow transplant (BMT). Male WAG/Riji/MCV rats received total body irradiation and a regimen of cyclophosphamide (CTX) in preparation for bone marrow transplant. While one group of animals remained untreated, the remainders were subdivided into three groups, each of them receiving either the ANG II receptor blocker or one of the two ACE inhibitors (Captopril or Enalapril). Each of the three drugs was administered orally from 11 days before the transplant up to 56 days post transplant. At sacrifice time the irradiated rats receiving only CTX showed a chronic pneumonitis with septal fibrosis and vasculitis affecting, in particular, small caliber pulmonary arteries and arterioles. Their lung content of hydroxyproline was also markedly elevated in association with the lung concentrations of thromboxane (TXA2) and prostaglandin (PGI(2)), (two markers of pulmonary endothelial damage). A significant increase of alpha actomyosin staining was observed in vessels, septa and macrophages of the same animals which also overexpressed TGF-beta. When L 158,809, Captopril and Enalapril were added to the radiation and cytoxan treatment, a significant amelioration of the histological damage as well as the overexpression of alpha SMA was observed. Lung concentrations of hydroxyproline, PGI(2), TXA2 and TGF-beta were also observed in these animals so that the values of these compounds were closer to those measured in untreated control rats than to their irradiated and cytoxan treated counterparts. Angiotensin II plays an important role in the regulation of TGF-beta and alpha SMA, two proteins involved in the pathogenesis of pulmonary fibrosis. The finding that ACE inhibitors or ANG II receptor blockers protect the lungs from radiation induced pneumonitis and fibrosis reaffirms the role that ANG II plays in this inflammatory process and suggests an additional indication of treatment of this condition, thus opening a new potential pharmacologic use of these drugs.

Background: Heparin remains the drug most commonly used for anticoagulation in continuous renal replacement therapies (CRRTs). However, in patients with hypercoagulability, heparin is insufficient or, in cases with an increased risk of bleeding or thrombocytopenia, it may be contraindicated. Epoprostenol, a potent vasodilator, antithrombotic and antiplatelet agent, could be an alternative., Patients and Methods: We studied the records of patients treated under continuous venovenous hemodiafiltration in an academic tertiary hospital of 900 beds, between January 2000 and June 2003. Epoprostenol was prescribed to patients with (i) filter hypercoagulability, defined as consumption of 2 or more filters in the last 24 hours; (ii) low platelet count; or (iii) recent severe hemorrhage., Results: Thirty-eight out of 248 (15%) patients who were under CRRT received epoprostenol for more than 72 hours. Epoprostenol was indicated due to filter hypercoagulability in 48%, thrombocytopenia in 68% (7 patients both) and hemorrhage in 3% of cases. The overall time for epoprostenol therapy was 9,749 hours. The mean filter duration previous to epoprostenol was 23 +/- 12 hours and after administering this drug 38.2 +/- 11.9 hours (p = 0.0001). In 6 patients, heparin and epoprostenol were simultaneously administered. The adverse effects were hemorrhage, which presented in 7 patients (18%) and a fall in blood pressure in another 7 (18%), which recovered in the next 24 hour after starting treatment. Cost analysis demonstrates some advantage with epoprostenol in patients with increased tendency to clotting., Conclusions: Epoprostenol may be safely used to prevent clotting of the extracorporeal circuits, either alone in patients with thrombocytopenia and/or increased risk of bleeding, or in combination with heparin in states of hypercoagulability.