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Chronic traumatic encephalopathy (CTE) is associated with repeated traumatic brain injuries (TBI) and is characterized by cognitive decline and the presence of neurofibrillary tangles (NFTs) of the protein tau in patients’ brains. Here we provide direct evidence that cell-scale mechanical deformation can elicit tau abnormalities and synaptic deficits in neurons. Using computational modeling, we find that the early pathological loci of NFTs in CTE brains are regions of high deformation during injury. The mechanical energy associated with high-strain rate deformation alone can induce tau mislocalization to dendritic spines and synaptic deficits in cultured rat hippocampal neurons. These cellular changes are mediated by tau hyperphosphorylation and can be reversed through inhibition of GSK3β and CDK5 or genetic deletion of tau. Together, these findings identify a mechanistic pathway that directly relates mechanical deformation of neurons to tau-mediated synaptic impairments and provide a possibly exploitable therapeutic pathway to combat CTE.

The coronavirus disease 2019 (COVID-19) pandemic has brought to forefront the large morbidity, mortality, and complications that viral illnesses can cause. For athletes, viral illnesses can be disruptive toward their participation in youth sports. This article outlines the details of how the most common viral illnesses affect the youth athlete and youth sports, including COVID-19, non–COVID-19 upper respiratory infections, influenza, Epstein-Barr virus, varicella, herpes, and other dermatologic infections. In this article, we review current available guidelines and recommendations on how to handle these infections in athletes during sports as well as return-to-play recommendations. [Pediatr Ann. 2021;50(11):e454–e460.]

Purpose of Review To describe different sports-specific and generalized strategies for prevention of overuse injuries in the youth athlete, and additionally, to review recent discussions of early sport specialization as it relates to pediatric and adolescent overuse injuries. Recent Findings Youth athletes are at an increased risk for developing overuse injuries due to their immature nervous and musculoskeletal systems and conditions unique to youth sports. Risk factors can be intrinsic or extrinsic to the athlete, and modified by sport or non-sport factors. Critical to preventing overuse injuries is attention to rates of load in training and recovery. Despite evidence against early sport specialization, it remains unclear whether youth specialization is an independent risk factor driving negative outcomes including overuse injuries, or whether it is the associated training loads and conditions. Summary In order to provide evidence-based and sport-specific guidelines to preventing overuse injuries, we are in need of more robust, specific, and prospective studies.

Background Malignant phyllodes tumors of the breast have traditionally been treated with surgical excision. Recently, the use of adjuvant radiotherapy has been advocated to reduce the risk of local recurrence; however, this recommendation is controversial in the absence of consistent outcome data. We hypothesize that there has been a trend toward increased utilization of adjuvant radiotherapy for malignant phyllodes tumors despite its uncertain effect on outcomes. Methods Using the National Cancer Data Base, predictors of radiotherapy utilization were examined for women with malignant phyllodes from 1998 to 2009. Kaplan–Meier and Cox regression models were generated to determine the effect of radiotherapy on local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Results Of the 3,120 patients with malignant phyllodes, 57 % underwent breast conservation surgery and 42 % underwent mastectomy. Overall, 14.3 % of women received adjuvant radiotherapy. Utilization of radiotherapy doubled over the study period (9.5 % in 1998–1999 vs. 19.5 % in 2008–2009, p  < 0.001). Women were significantly more likely to receive radiotherapy if they were diagnosed later in the study, were age 50–59 years old, had tumors >10 cm, or had lymph nodes removed. For the 1,774 patients with available recurrence data, overall recurrence was 14.1 %, and LR was 5.9 %. In adjusted models, adjuvant radiotherapy reduced LR (aHR 0.43, 95 % CI 0.19–0.95) but did not impact DFS or OS after 53 months’ median follow-up. Conclusions Utilization of adjuvant radiotherapy for malignant phyllodes doubled from 1998 to 2009. Radiotherapy significantly reduced LR but had no effect on DFS or OS.

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Adult human endometrial derived stem cells (HEDSC), a readily obtainable type of mesenchymal stem‐like cell, were used to generate dopaminergic cells and for transplantation. Cells expressing CD90, platelet derived growth factor (PDGF)‐Rβ and CD146 but not CD45 or CD31 were differentiated in vitro into dopaminergic neurons that exhibited axon projections, pyramidal cell bodies and dendritic projections that recapitulate synapse formation; these cells also expressed the neural marker nestin and tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis. Whole cell patch clamp recording identified G‐protein coupled inwardly rectifying potassium current 2 channels characteristic of central neurons. A 1‐methyl 4‐phenyl 1,2,3,6‐tetrahydro pyridine induced animal model of PD was used to demonstrate the ability of labelled HEDSC to engraft, migrate to the site of lesion, differentiate in vivo and significantly increase striatal dopamine and dopamine metabolite concentrations. HEDSC are a highly inducible source of allogenic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model.

The treatment of thin melanoma (Breslow thickness <1.0 mm) may include sentinel lymph node (SLN) biopsy (SLNB). The validity of SLNB for thin melanoma remains widely debated. The purpose of this study was to elucidate pathologic factors that are predictive of SLN positivity. A retrospective analysis of a prospective database revealed 1,199 patients diagnosed with primary cutaneous melanoma. Multiple logistic regression was used to determine an association between pathologic factors and SLN positivity. Thin melanomas were identified in 469 patients (39%). Of these, 147 patients (31%) underwent SLNB. Positive SLNs were found in 16 patients (11%). Multiple logistic regression demonstrated that both ulceration (odds ratio, 5.27; P = .047) and thickness (odds ratio, 46.69; P = .022) were associated with SLN positivity. Patients with thin melanomas >.75 mm and/or ulceration should be considered for SLNB.

Background The purpose of this study was to report our experience with sentinel lymph node dissection (SLND) for papillary thyroid carcinoma, to evaluate the feasibility and safety of the procedure, and to examine its potential utility as a guide for central neck dissection. Materials and Methods A retrospective chart review of patients undergoing total thyroidectomy from January 1998 thru January 2010 was conducted. Intratumoral injection of blue dye was used to identify the SLN. Central neck dissection (CND) was performed if the SLN was positive on frozen section. Locally advanced disease, previous thyroid surgery, or lymphadenopathy on preoperative imaging or intraoperative palpation were exclusion criteria. Results A total of 211 patients underwent SLN mapping. Of these, 165 patients (78%) were female and 46 (22%) were male. Also, 75 (36%) were ≤45 years of age, and 136 (64%) were older than 45. Tumors were ≤2.0 cm (T1) in 142 patients (67%), 2–4 cm (T2) in 35 patients (17%), >4 cm with minimal invasion (T3) in 32 patients (15%), and locally invasive (T4) in 2 patients (1%). At least 1 blue node was found in 192 patients (91%). Also, 47 patients had a positive SLN on frozen section, with an additional 24 node-positive patients on permanent section, for a total of 71 (37%). There were 43 patients (91%) who underwent central neck dissection; 26 (60%) had additional metastases. Conclusions Sentinel lymphadenectomy for papillary thyroid carcinoma is feasible, safe, and can identify patients who may benefit from central neck dissection.

Breast cancer molecular subtypes, categorized jointly by hormone receptors (HR) and human epidermal growth factor-2 (HER2), are utilized to guide systemic therapy. We hypothesized distinct patterns of de novo metastasis and overall survival by molecular subtype using a retrospective cohort of 399,772 women in the National Cancer Database diagnosed with first primary invasive breast cancer between 2010 and 2014, of whom 13,924 were diagnosed with de novo metastasis from 2010 to 2013 and had follow up data. The relationship of molecular subtype with patient and tumor characteristics, including site of de novo metastasis, were examined using Chi-squared tests. Kaplan–Meier and Cox proportional hazards analyses were used to examine overall survival by molecular subtype. Bone was the most frequent de novo metastatic site for all molecular subtypes. Compared to HR+/HER2−, patients with HR−/HER2+ experienced 4.5, 3.0, and 6.0 times the de novo brain, lung, and liver metastasis respectively. In survival analyses of women diagnosed with de novo metastasis, the mortality risk relative to HR+/HER2− was twice as high for triple-negative (hazard ratio = 2.02, 95% CI 1.89–2.16) and modestly lower for HR+/HER2+ (hazard ratio = 0.83, 95% CI 0.78–0.88). The median survival difference between metastatic patients with and without chemotherapy was 28.6 months in HR+/HER2+ and 28.2 months in HR−/HER2+, but only 10.9 months in triple-negative and 5.2 months in HR+/HER2−. In conclusion, despite unfavorable patterns of de novo metastasis, HER2+ breast cancers had relatively better survival in recent years, probably due to treatment differences. Utilizing molecular subtype and site of de novo metastasis may predict prognosis and guide treatment.

BackgroundThe American Joint Committee on Cancer (AJCC) 8th edition staging system for breast cancer has been validated in the upfront surgery setting, but has not been examined for its prognostic impact on patients undergoing neoadjuvant chemotherapy.MethodsThe National Cancer Data Base was used to identify patients with invasive unilateral breast cancer from 2010 to 2015 who underwent neoadjuvant chemotherapy. AJCC clinical stage classification was compared between the 7th and 8th editions. Receiver operating characteristic analysis of Kaplan–Meier overall survival (OS) was used to determine the predictive fit of the 7th and 8th edition staging in estimating OS.ResultsAJCC 7th and 8th clinical staging assignments were applied to 57,466 patients who underwent neoadjuvant chemotherapy for stage I–III breast cancer from 2010 to 2015. Overall, 37.5% of patients were downstaged and 27.8% were upstaged from the 7th to the 8th edition classification. Kaplan–Meier curves comparing 7th and 8th edition staging differed in OS rates, with a mean follow-up time of 41.5 months. AJCC 8th edition prognostic staging was a better predictor of OS than 7th edition anatomic staging for both clinical stage [area under the curve (AUC) 0.67 vs. 0.62, p < 0.01] and pathological stage (AUC 0.70 vs. 0.66, p < 0.01).ConclusionsSixty-five percent of patients have a shift in clinical stage in the AJCC 8th edition. AJCC 8th edition staging has better predictive value for OS than 7th edition staging. While validation of these findings with an independent dataset is needed, 8th edition staging will help improve prognostic modeling in patients undergoing neoadjuvant chemotherapy.