Decreased Incidence of Hirschsprung-Associated Enterocolitis During COVID-19 Across United States Children's Hospitals

BackgroundThe Coronavirus Disease 2019 pandemic provided a natural experiment to study the effect of social distancing on the risk of developing Hirschsprung's Associated Enterocolitis (HAEC).MethodsUsing the Pediatric Health Information System (PHIS), a retrospective cohort study of children (<18 years) with Hirschsprung's Disease (HSCR) across 47 United States children's hospitals was performed. The primary outcome was HAEC admissions per 10,000 patient-days. The exposure (COVID-19) was defined as April 2020–December 2021. The unexposed (historical control) period was April 2018–December 2019. Secondary outcomes included sepsis, bowel perforation, intensive care unit (ICU) admission, mortality, and length of stay.ResultsOverall, we included 5707 patients with HSCR during the study period. There were 984 and 834 HAEC admissions during the pre-pandemic and pandemic periods, respectively (2.6 vs. 1.9 HAEC admissions per 10,000 patient-days, incident rate ratio [95% confidence interval]: 0.74 [0.67, 0.81], p < 0.001). Compared to pre-pandemic, those with HAEC during the pandemic were younger (median [IQR]: 566 [162, 1430] days pandemic vs. 746 [259, 1609] days pre-pandemic, p < 0.001) and more likely to live in the lowest quartile of median household income zip codes (24% pandemic vs. 19% pre-pandemic, p = 0.02). There were no significant differences in rates of sepsis (6.1% pandemic vs. 6.1% pre-pandemic, p > 0.9), bowel perforation (1.3% pandemic vs. 1.2% pre-pandemic, p = 0.8), ICU admissions (9.6% pandemic vs. 12% pre-pandemic, p = 0.2), mortality (0.5% pandemic vs. 0.6% pre-pandemic, p = 0.8), or length of stay (median [interquartile range]: 4 [(Pastor et al., 2009; Gosain and Brinkman, 2015) 2,112,11 days pandemic vs. 5 [(Pastor et al., 2009; Tang et al., 2020) 2,102,10 days pre-pandemic, p = 0.4).ConclusionsThe COVID-19 pandemic was associated with significantly decreased incidence of HAEC admissions across US children's hospitals. Possible etiologies such as social distancing should be explored.Level of evidenceII.     

Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial

ObjectivesPreclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression.DesignRandomized double-blind placebo-controlled delayed-start study.Setting and ParticipantPatients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials.gov, NCT03038035).MethodsThe primary outcome measure was occurrence of serious adverse events (SAEs) at 6 months. Secondary outcomes included the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS-Cog) and other assessment scales.ResultsThere was no significant difference in the risk of SAEs between early and delayed starters at month (M) 6 (22.6% vs 27.0%, risk difference ?4.4%, 90% CI –16.9% to 8.3%). Similarly, there was no significant difference in the risk of adverse events and the occurrence of stroke or vascular events between early and delayed starters throughout the 12-month study period. Early starters did not differ significantly on ADAS-Cog from delayed starters at M6 [mean difference (MD) ?1.0, 95% CI –3.3 to 1.3] and M12 (MD –2.35, 95% CI –5.45 to 0.74) on intention-to-treat analysis. Other cognitive assessment scales did not show significant differences.Conclusions and ImplicationsThis study of 125 persons with dementia found no evidence of a significant increase in adverse events between MLC901 and placebo, thus providing support for further studies on both efficacy and safety. Analyses suggest the potential of MLC901 in slowing down AD progression, but this requires further confirmation in larger and longer studies using biomarkers for AD.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Shear-bond strength of different Self-Etching adhesive systems to dentin with or without laser irradiation before photopolymerization (A comparative Study)

This study aimed at comparing shear-bond strength (SBS) of different self-etching adhesive systems (Clearfil S³ Bond Plus, G-Premio BOND and IBond) to dentin without or with diode-laser irradiation before photo-polymerization and to determine the effect of storage and thermo-cycling on SBS of adhesive systems. Methods: The buccal surface of 84 extracted maxillary premolars was grounded to create flat surface. The specimens were allocated into 3 groups (n = 28) depending upon the adhesive systems, then each group was divided into two sub-group (I, II) (n = 14). After the placement of respective adhesive systems on the flat surface, adhesive system in group I was photo-polymerized immediately, while in group II, the adhesive systems were exposed to diode-laser before photo-polymerization. Composite cylinder (4 mm in diameter and 2 mm height) was built on the flat surface of each specimen. Then group I and II were divided into two sub-groups (n = 7) according to the storage time and thermo-cycling (1 day without thermo-cycling or 72 days with thermo-cycling) then all the specimens were stored in distilled water. The SBS was measured at the end of storage period. ANOVA, Duncan’s Multiple Range Test and independent t-test “P ≤ 0.05” were used for data analysis. Results: G-premio BOND showed the highest mean value of SBS followed by Clearfil S³ Bond plus without significant difference between them, while IBond revealed the least mean value. Laser irradiation had positive effect on the bond-strength of all tested adhesive systems. The results also showed that the storage with thermo-cycling had negative effect on the bond-strength in groups without laser irradiation for all tested adhesive systems, while for groups with laser irradiation, the reduction in the bond-strength of all tested adhesive systems was not significant. Conclusion: Diode-laser application prior to photo-polymerization of self-etch adhesive systems significantly increased the bond-strength to dentin and can increase the durability of composite adhesion.     

Minimum information to report about a flow cytometry experiment on extracellular vesicles: Communication from the ISTH SSC subcommittee on vascular biology

The Extracellular Vesicle Flow Cytometry Working Group ( http://www.evflowcytometry.org ) is formed by members of the International Society for Extracellular Vesicles (ISEV), the International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH). This working group of flow cytometry experts develops guidelines for best practices regarding flow cytometry detection of extracellular vesicles. To improve rigor and standardization, this working group published a framework outlining the minimal information to report about a flow cytometry experiment on extracellular vesicles (MIFlowCyt-EV) in the Journal of Extracellular Vesicles, the ISEV journal, in 2020. In parallel, an article explaining MIFlowCyt-EV was published in Cytometry Part A, one of the ISAC journals, and now will be introduced to the ISTH as an SSC Communication in the Journal of Thrombosis and Haemostasis. The goal of this SSC Communication is to explain why flow cytometry is becoming the instrument of choice to characterize single extracellular vesicles, the obstacles that have been identified and (mostly) overcome by developing procedures to calibrate flow cytometers, and the relevance of reporting minimal information to improve reliability and reproducibility of experiments in which flow cytometers are used for characterization of extracellular vesicles.     

讨论式教学法在温病学中的教学设计——以温病的祛湿法为例

文章以温病的治法祛湿法为例,提出讨论式教学法的教学设计,包括建立"三人为师"规则、"发言签"规则,营造讨论气氛,角色分配包括向导、刺头、记录员、法官、汇报人,然后按照"领结模型"展开讨论,最后按照表达意愿、思维技能、学生间互动、内容知识掌握情况等进行评估,旨在培养学生温病学临床思维能力与团队协作能力。