Assessment of proadrenomedullin as diagnostic or prognostic biomarker of acute appendicitis in children with acute abdominal pain

BackgroundAcute appendicitis (AA) is one of the most frequent surgical pathologies in pediatrics.ObjectivesTo investigate the utility of proadrenomedullin (pro-ADM) for the diagnosis of AA.MethodsProspective, analytical, observational, and multicenter study conducted in 6 pediatric emergency departments. Children up to 18 years of age with suspected AA were included. Clinical, epidemiological, and analytical data were collected.ResultsWe studied 285 children with an average age of 9.5 years (95% confidence interval [CI], 9.1–9.9). AA was diagnosed in 103 children (36.1%), with complications in 10 of them (9.7%). The mean concentration of pro-ADM (nmol/L) was higher in children with AA (0.51 nmol/L, SD 0.16) than in children with acute abdominal pain (AAP) of another etiology (0.44 nmol/L, SD 0.14; p < 0.001). This difference was greater in complicated cases compared with uncomplicated AA (0.64 nmol/L, SD 0.17 and 0.50 nmol/L, SD 0.15, respectively; p = 0.005). The areas under the receiver-operating characteristic curves were 0.66 (95% CI, 0.59–0.72) for pro-ADM, 0.70 (95% CI, 0.63–0.76) for C-reactive protein (CRP), 0.84 (95% CI, 0.79–0.89) for neutrophils, and 0.84 (95% CI, 0.79–0.89) for total leukocytes. The most reliable combination to rule out AA was CRP ≤1.25 mg/dL and pro-ADM ≤0.35 nmol/L with a sensitivity of 96% and a negative predictive value of 93%.ConclusionChildren with AA presented higher pro-ADM values than children with AAP of other etiologies, especially in cases of complicated AA. The combination of low values of pro-ADM and CRP can help to select children with low risk of AA.     

A Biomechanical Foot-Worn Device Improves Total Knee Arthroplasty Outcomes

Background

Biomechanics after total knee arthroplasty (TKA) often remain abnormal and may lead to prolonged postoperative recovery. The purpose of this study is to assess a biomechanical therapy after TKA.

男性乳腺癌38例临床病理分析

目的 分析男性乳腺癌的临床病理及分子分型特点。方法 回顾分析宁波市临床病理诊断中心2013年1月至2019年3月38例男性乳腺癌病例的临床病理和分子分型资料。结果 38例男性乳腺癌病人，占同期乳腺癌病人0.83%，中位年龄68.5（24～88）岁，病灶位于左侧20例，位于右侧18例。其中29例为浸润性导管癌，2例为分泌性癌，1例为实性乳头状癌伴微浸润， 2例为导管内乳头状癌伴微浸润，4例为包裹性乳头状癌（其中2例伴微浸润）。浸润性导管癌组织学分级Ⅰ级2例，Ⅱ级20例，Ⅲ级7例。16例伴淋巴结转移。免疫组化染色：36例ER 阳性，35例PR阳性。分子分型Luminal A型18例，Luminal B型16例，基底细胞型2例。结论 男性乳腺癌少见，发病年龄较晚，临床分期较高，预后较差，且发生第2种原发性癌的可能性增加，加强对其认识，争取早期诊断、治疗及监测非常重要。男性乳腺癌仍须扩大样本量进一步研究。     

Conditions and extent of volatile loss from the Moon during formation of the Procellarum basin

Rocks from the lunar interior are depleted in moderately volatile elements (MVEs) compared to terrestrial rocks. Most MVEs are also enriched in their heavier isotopes compared to those in terrestrial rocks. Such elemental depletion and heavy isotope enrichments have been attributed to liquid–vapor exchange and vapor loss from the protolunar disk, incomplete accretion of MVEs during condensation of the Moon, and degassing of MVEs during lunar magma ocean crystallization. New Monte Carlo simulation results suggest that the lunar MVE depletion is consistent with evaporative loss at 1,670 ± 129 K and an oxygen fugacity +2.3 ± 2.1 log units above the fayalite-magnetite-quartz buffer. Here, we propose that these chemical and isotopic features could have resulted from the formation of the putative Procellarum basin early in the Moon’s history, during which nearside magma ocean melts would have been exposed at the surface, allowing equilibration with any primitive atmosphere together with MVE loss and isotopic fractionation.

Returned samples of basaltic rocks from the Moon provided evidence decades ago that the Moon is depleted in volatile elements compared to the Earth (1), with lunar basalt abundances of moderately volatile elements (MVEs) being ∼1/5 that of terrestrial basalt abundances for alkali elements and ∼1/40 for other MVE, such as Zn, Ag, In, and Cd (2). The theme of lunar volatiles thus seemed settled. Yet, the unambiguous detection in 2008 of lunar indigenous hydrogen and other volatile elements, such as F, Cl, and S in pyroclastic glasses (3), heralded a new era of research into lunar volatiles, overturning the decades-old paradigm of a bone-dry Moon (e.g., refs. 4 and 5). Here, we define volatile elements as those with 50% condensation temperatures below these of the major rock-forming elements Fe, Mg, and Si (6). This paradigm shift was accompanied by new measurements of volatile stable isotope compositions (e.g., H, C, N, Cl, K, Cr, Cu, Zn, Ga, Rb, and Sn) in a wealth of bulk lunar samples (7–18) and in the mineral phases and melt inclusions they host (19–28). These studies have shown that the stable isotope compositions of most MVEs (e.g., K, Zn, Ga, and Rb) are enriched in their heavier isotopes with respect to the bulk silicate Earth (BSE) (9, 11, 13–15, 17). Such heavy isotope enrichment is associated with elemental depletion, which has been variously attributed to liquid–vapor exchange and vapor loss from the protolunar disk (17, 18), incomplete accretion of MVEs during condensation of the Moon (13, 29, 30), and degassing of these elements during lunar magma ocean crystallization (9, 11, 14, 15, 25, 31). Almost all these hypotheses have typically assumed that the MVE depletions and associated MVE isotope fractionations are relevant to the whole Moon. However, our lunar sample collections are biased, as all Apollo and Luna returned samples come from the lunar nearside from within or around the anomalous Procellarum KREEP Terrane (PKT) region (e.g., ref. 32), where KREEP stands for enriched in K, REEs, and P. Barnes et al. (26) proposed that the heavy Cl isotope signature measured in KREEP-rich Apollo samples resulted from metal-chloride degassing from late-stage lunar magma ocean melts in response to a large crust-breaching impact event, spatially associated with the PKT region, which facilitated exposure of these late-stage melts to the lunar surface. Here, we further investigate whether a localized impact event could have been responsible for the general MVE depletion and heavy MVE isotope enrichment measured in lunar samples.     

Efficacy and safety of modafinil in patients with idiopathic hypersomnia without long sleep time: a multicenter,randomized, double-blind,placebo-controlled,parallel-group comparison study

BackgroundFew treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time.MethodsThis multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety.ResultsIn total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26–6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred.ConclusionModafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time.Clinical trial registrationJapicCTI; 142539.     

Reliability and validity of the Japanese version of the Biological Rhythms Interview of assessment in neuropsychiatry-self report for delayed sleep-wake phase disorder

ObjectiveThe Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) might be applicable for assessing delayed sleep-wake phase disorder (DSWPD). We aimed to investigate the reliability and validity of the Japanese version of the BRIAN self-report (J-BRIAN-SR) in DSWPD patients and determine a cutoff score to identify the presence of the disorder.MethodsWe enrolled 60 newly diagnosed DSWPD outpatients and 64 age-matched healthy controls. We used Cronbach's alpha for internal reliability to evaluate J-BRIAN-SR. We confirmed the reliability of the A test and re-test using Pearson's correlation coefficient in the controls. We used confirmatory factor analysis to evaluate the factor structure of J-BRIAN-SR and referenced the Morningness-Eveningness Questionnaire (MEQ) to check concurrent validity. We analyzed the receiver operating characteristic curve (ROC) to determine the J-BRIAN-SR cutoff point for the presence of DSWPD.ResultsThe 18-component scores of the J-BRIAN-SR had an overall reliability coefficient (Cronbach's alpha) of 0.82. We confirmed a high test-retest reliability using an intraclass correlation coefficient (r = 0.84). The correlation between J-BRIAN-SR and MEQ was 0.38 (p = 0.003). The J-BRIAN-SR that we extracted by exploratory factor analysis consisted of three factors. A score of 40 points provided a sensitivity of 80.0% and a specificity of 75.6% for the positivity of DSWPD.ConclusionsThe results of the present study revealed that J-BRIAN-SR is a valid and reliable instrument for screening and evaluating the severity of DSWPD. Our findings will be useful to physicians and patients in Japan and those in clinical settings.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.