Τετάρτη 20 Ιανουαρίου 2021

IL-25 (IL-17E) in epithelial immunology and pathophysiology

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IL-25, also known as IL-17E, is a unique cytokine of the IL-17 family. Indeed, IL-25 exclusively was shown to strongly induce expression of the cytokines associated with type 2 immunity. Although produced by several types of immune cells, such as T cells, dendritic cells, or group 2 innate lymphoid cells, a vast amount of IL-25 derives from epithelial cells. The functions of IL-25 have been actively studied in the context of physiology and pathology of various organs including skin, airways and lungs, gastrointestinal tract, and thymus.
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Improving Executive Function of Children with Autism Spectrum Disorder through Cycling Skill Acquisition

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Purpose Executive dysfunction has been widely reported in children with autism spectrum disorder (ASD). While studies have clearly documented the cognitive benefits of physical exercise on cognition in children, similar studies in children with ASD are scarce. The purpose of this study was to compare the impact of cognitively engaging exercise and non-cognitively engaging exercise on executive function in children with ASD. Methods Sixty-two children diagnosed with ASD (50 males and 12 females, Mage = 9.89±1.53 yr, Mheight = 1.43 ± 0.15 m, and Mweight = 44.69 ± 11.96kg) were randomly assigned into three groups: learning to ride a bicycle (n = 22), stationary cycling (n = 20) and control (n = 20). Four executive function components (planning, working memory, flexibility and inhibition) were assessed. Results Results revealed significant improvements in all executive function components in the learning to ride a bicycle group (ps <.05 but not in the other two groups after controlling for age and iq. conclusion our findings highlight value of cognitive engagement exercise programs designed to improve cognition children with asd. corresponding author detail: dr. andy c.y. tse rm d4-2 block d4 lo ping road tai po n.t. hong kong. tel: email: andytcy authors declare that results study are presented clearly honestly without fabrication falsification or inappropriate data manipulation presentation result does constitute endorsement by acsm. declared no potential conflicts interest respect research authorship publication this article. work described paper was supported a grant from grants council kong special administrative region china no. eduhk accepted publication: january american college sports medicine>
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Factors Protecting against a Decline in Physical Activity during the COVID-19 Pandemic

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Purpose The spread of COVID-19 and the associated stay-at-home orders and shutdowns of gyms and fitness centers has drastically influenced health behaviors leading to widespread reductions in physical activity (PA). The recent Call to Action from the American College of Sports Medicine has promoted "innovative strategies to promote PA during the COVID-19 pandemic". We aimed to identify individual-level factors that protected against declines in PA levels amid the COVID-19 restrictions. Methods We utilized the Pennington Biomedical COVID-19 Health Behaviors Survey for our analyses and used mixed-effect linear and generalized linear models to estimate the effects of individual-level factors on changes in PA levels during the COVID-19 restrictions. Results Participants (n=4,376) provided information on PA behaviors before and during the COVID-19 shutdown. Overall, PA levels declined by a mean (SD) of 112 (1,460) MET minutes/week during the COVID-19 shutdown; however, changes in PA were heterogeneous, with 55% of the participants reporting increases in or maintenance of PA during that time. Several social and demographic factors were significantly related to declines in PA, including high pre-pandemic PA levels, living alone (difference=118 MET minutes/week), low household income (difference between the highest and lowest income group=363 MET minutes/week), COVID-19-related changes in income (difference=110 MET minutes/week), and loss of employment (difference=168 MET minutes/week). Substitution of pre-pandemic gym attendance with the purchase and use of home exercise equipment or exercise through virtual fitness platforms promoted increases in PA during the COVID-19 shutdown. Conclusions While promoting PA through the COVID-19 pandemic, it is important to consider demographic factors, which greatly influence health behaviors and implementation of, and access to, replacement behaviors. Promotion of such strategies could help maintain PA levels during potential future stay-at-home orders. * Denotes co-first authorship Accepted for Publication: 21 December 2020 Corresponding Author: Leanne M. Redman, PhD, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, T. 1-225-763-0947 E. leanne.redman@pbrc.edu This work was partially supported by a NORC Center Grant # P30DK072476 entitled "Nutrition and Metabolic Health Through the Lifespan" sponsored by NIDDK. In addition, this work was supported in part by U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. C.H. is supported by an NIH NIDDK National Research Service Award (T32DK064584). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflict of Interest. None of the authors declare a conflict of interest. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. © 2021 American College of Sports Medicine
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In Vivo Visualization of Tissue Damage Induced by Percutaneous Muscle Biopsy via Novel High-Resolution MR Imaging

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Purpose Percutaneous muscle biopsy is the gold standard for tissue assessment in clinical practice and scientific studies. The aim of this study was to assess and quantify the ensuing tissue damage by in vivo magnetic resonance imaging (MRI). Methods In this prospective study we enrolled 22 healthy participants, who underwent MRI of the thigh musculature about one week after a percutaneous muscle biopsy of the vastus lateralis muscle. A total of 17 participants also volunteered for a second MR-examination two weeks after biopsy. Volumes of SWI lesions and muscle edema were assessed by susceptibility-weighted imaging (SWI) and T2-weighted MRI, respectively, after manual segmentation by two independent readers. For quantitative in vivo hematoma volume assessment, we additionally determined signal changes induced by experimental hematoma in an ex vivo model. Results Mean overall volume of SWI lesions one week after biopsy was 26.5 ± 21.7 μl, accompanied by a mean perifocal edema volume of 790.1 ± 591.4 μl. In participants who underwent two examinations mean volume of SWI lesions slightly decreased from 29.8 ± 23.6 μl to 23.9 ± 16.8 μl within one week (p=0.13). Muscle edema volume decreased from 820.2 ± 632.4 μl to 359.6 ± 207.3 μl at the same time (p=0.006). By calibration with the ex vivo findings, signal alterations on SWI corresponded to a blood volume of approximately 10 - 50 μl. Conclusion Intramuscular hematoma and accompanying muscle edema after percutaneous biopsy are small and decrease rapidly within the first two weeks. These in vivo findings underline the limited invasiveness of the procedure. Accepted for Publication: 11 December 2020 Correspondence: Tim Hilgenfeld, MD, Department of Neuroradiology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Email: Tim.Hilgenfeld@med.uni-heidelberg.de Supported in part by the German Research Council (SFB 1118, S.H.; SFB 1158, M.B.). The authors have no commercial or financial conflicts of interest to declare. The results are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation and do not constitute endorsement by the American College of Sports Medicine. © 2021 American College of Sports Medicine
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Maximal Oxygen Uptake Is Underestimated during Incremental Testing in Hypertensive Older Adults: Findings from the HAEL Study

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Purpose The present cross-sectional study aimed to investigate whether a maximal oxygen uptake (VO2max) verification phase (VER) could improve the accuracy of a previous graded exercise test (GXT) to assess individual VO2max in hypertensive individuals. Methods Thirty-three older adults with hypertension (24 women) taking part in the Hypertension Approaches in the Elderly Study (NCT03264443) were recruited. Briefly, after performing a treadmill GXT to exhaustion, participants rested for 10 min and underwent a multistage VER to confirm GXT results. Individual VO2max, respiratory exchange ratio (RER), maximal heart rate (HRmax), and rating of perceived exertion (RPE) were measured during both GXT and VER tests. Mean values were compared between bouts using paired sample t-tests and VO2max was also compared between GXT and VER on an individual basis. Results Testing was well tolerated by all participants. Both absolute (p=0.011) and relative (p=0.014) VO2max values were higher in VER than in GXT. RER (p
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Sex Differences in Cardiometabolic Health Indicators following HIIT in Patients with Coronary Artery Disease

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Purpose Cardiorespiratory fitness (CRF) is an independent predictor of mortality, and females typically achieve smaller improvements in CRF than males following exercise-based cardiac rehabilitation (CR). High-intensity interval training (HIIT) has been shown to produce superior improvements in CRF than traditional CR, but the sex-differences are unknown. The purpose of this systematic review and meta-analysis was to evaluate sex-differences for changes in CRF and cardiometabolic health indicators following HIIT in adults with coronary artery disease (CAD). Methods and Results A systemic search of 5 electronic databases for studies examining the effect of HIIT on measured CRF and cardiometabolic health indicators in adults with CAD was performed. Data (published and unpublished) from 14 studies were included in the meta-analyses with ~8-fold greater male than female participation (n=836 vs. n=103). Males with CAD achieved a near significant absolute improvement in CRF (mean difference [MD]: 1.07, 95% CI: -0.08 to 2.23 mL/kg/min, p=0.07) following HIIT when compared to control; there were insufficient data to conduct such an analysis in females. Significantly smaller improvements in CRF were experienced by females than males (MD: -1.10, 95% CI: -2.08 to -0.12 mL/kg/min; p=0.03); there was no sex-difference for the relative (percentage) change in CRF following HIIT. Females achieved significantly smaller reductions in body mass index (MD: -0.25, 95% CI: -0.03 to -0.47 kg/m2; p=0.02) and fasting blood glucose (MD: -0.38, 95% CI: -0.05 to -0.72; p=0.03); no se x-differences were observed for other cardiometabolic health indicators. Conclusion There are no sex-differences for relative improvements in CRF following HIIT; however, females are greatly underrepresented in trials. Future studies should increase female participation and perform sex-based analyses to determine sex-specific outcomes with HIIT. Accepted for Publication: 4 December 2020 Address for correspondence: Dr. Kimberley L. Way, Deakin University, 221 Burwood Highway, Burwood, Victoria 3125, Australia. Phone: +1613.879.0407. Email: kim.way@deakin.edu.au. Twitter handle: @DrKimWay, @DrJenniferReed CONFLICT OF INTEREST. The authors received no funding to support the research and publication of this manuscript. The authors have no conflicts of interest to declare. The results of the present study do not constitute endorsement by ACSM are presented without fabrication, falsification, or inappropriate data manipulation. © 2021 American College of Sports Medicine
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KIT mutational status does not constitute an independent prognostic marker in cutaneous melanoma. A study on 688 Spanish patients

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imageNo abstract available
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Safety and efficacy of combination nivolumab plus ipilimumab

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imageCheckMate 218, a North American expanded access program (EAP), investigated nivolumab plus ipilimumab in patients with advanced melanoma. Safety and efficacy, including 2-year survival in clinically relevant patient subgroups, are reported. Eligible patients were aged ≥18 years with unresectable stage III/IV melanoma, an Eastern Cooperative Oncology Group performance status of 0/1, and no prior checkpoint inhibitors. Patients received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 cycles (induction) followed by nivolumab 3 mg/kg every 2 weeks (maintenance) until progression or unaccepta ble toxicity or a maximum of 48 weeks. Safety and overall survival (OS) data were collected. This EAP included 754 treated patients from the USA (n = 580) and Canada (n = 174). Median follow-up time was 17.8 months. All-grade and grade 3–4 treatment-related adverse events were reported in 96% and 53% of patients and led to treatment discontinuation in 36% and 26% of patients, respectively. OS rates at 12 and 24 months were 82% [95% confidence interval (CI) 79–84] and 70% (95% CI 66–74), respectively. Twenty-four-month OS rates were 63% in patients aged ≥75 years, 56% in patients with elevated lactate dehydrogenase levels, 73% in patients with BRAF wild-type tumors, 70% in patients with BRAF mutant tumors, and 56% in patients with mucosal melanoma. In this EAP, nivolumab plus ipilimumab demonstrated high survival rates and safety outcomes consistent with those from randomized clinical trials, further supporting the use of this combination for advanced melanoma across multiple subgroups.
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Novel response to neoadjuvant anti-PD1 therapy for a patient with retrocaval melanotic schwannoma

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imageMelanotic schwannoma is a rare nerve sheath tumor composed of melanin-producing Schwann cells with the potential for metastasis. These tumors can be associated with familial tumor syndromes and can cause significant symptoms related to nerve compression and mass effect. Due to the rarity of these lesions, they can be initially misidentified as melanocytomas, pigmented dermatofibrosarcoma protuberans, neurofibromas or malignant melanomas. Surgical excision is the mainstay of treatment with limited benefit from adjuvant systemic chemotherapy or radiation. Modern treatments with immune checkpoint blockad e have demonstrated significant improvements in progression-free and overall survival for a variety of cancer histologies; however, anti-PD1 therapy has yet to be evaluated in patients with melanotic schwannoma. This report demonstrates a significant improvement in symptomatology and tumor stability with neoadjuvant anti-PD1 therapy for a retrocaval melanotic schwannoma initially masquerading as malignant melanoma. This report demonstrates the potential benefit of a novel therapeutic option for patients with melanotic schwannoma.
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Postapproval trials versus patient registries: comparability of advanced melanoma patients with brain metastases

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imagePostapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF- MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval clinical trial patients was 8.7 (95% CI, 8.1–10.4) months compared to 7.2 (95% CI, 6.5–7.7) months (P 
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Life-threatening polymyositis with spontaneous hematoma induced by nivolumab in a patient with previously resected melanoma

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imageSingle-agent anti-PD1 antibodies are usually very well tolerated, but serious toxicity can still occur. Despite the PD-1 pathway seems to be relevant in the pathogenesis of immune-related myositis, anti-PD1-related myositis is generally a rare side effect of the treatment and usually not serious. However, its frequency is likely to increase as the use of immune checkpoint blockades. We present here a case of life-threatening polymyositis with associated spontaneous muscular hematoma in a patient treated with single-agent nivolumab in the adjuvant setting. Spontaneous hematoma is an extremely rare complica tion with unclear etiology of idiopathic myositis. Very few cases have been reported in the literature and their outcome has been often fatal. To our knowledge, this is the first case of autoimmune myositis and spontaneous heamatoma associated with the administration of single-agent checkpoint blockade. Anti-PD1 antibodies have changed the treatment landscape for a number of cancer entities in the past few years. When given as single agent they are usually very well tolerated, but serious rare toxicity can still occur. We present here a case of polymyositis with associated spontaneous muscular hematoma in a patient treated with single agent nivolumab.
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