Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

Early posterior vitreous detachment is associated with LAMA5 dominant mutation

Background: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.Materials and Methods: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members.Results: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported.Conclusions: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.     

Selective blocking laminoplasty in cervical laminectomy and fusion to prevent postoperative C5 palsy

BACKGROUND CONTEXT

Cervical laminectomy and fusion (CLF) is a common surgical option for multilevel cord compression. Postoperative C5 palsy occurrence after CLF has been a vexing problem for spine physicians. The posterior shift of the cord following laminectomy has been implicated as a major factor for postoperative C5 palsy, but attempts by spine surgeons to mitigate excessive shift while providing sufficient decompression have not been well reported.

Health Care Utilization After Ventricular Tachycardia Ablation: A Propensity Score-Matched Cohort Study

Background

Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy.

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

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The optimal timing for the interval to surgery after short course preoperative radiotherapy (5 ×5 Gy) in rectal cancer - are we too eager for surgery?

BackgroundThe improved overall survival (OS) after short course preoperative radiotherapy (SCPRT) using 5 × 5 Gy reported in the early rectal cancer trials could not be replicated in subsequent phase III trials. This original survival advantage is attributed to poor quality of surgery and the large differential in local recurrence rates, with and without SCPRT. Immuno-modulation during and after SCPRT and its clinical implications have been poorly investigated. We propose an alternative explanation for this survival benefit in terms of immunological mechanisms induced by SCPRT and the timing of surgery, which may validate the concept of consolidation chemotherapy.Material and methodsWe reviewed randomized controlled trials (RCTs) and studies of SCPRT from 1985 to 2019. We aimed to examine the precise timing of surgery in days following SCPRT and identify evidence for immune modulation, neo-antigens and memory cell induction by radiation.ResultsConsiderable variability is reported in randomised trials for median overall treatment time (OTT) from start of SCPRT to surgery (8–14 days). Only three early trials showed a benefit in terms of OS from SCPRT, although the level of benefit in preventing local recurrence was consistent across all trials. Different patterns of immune effects are observed within days after SCPRT depending on the OTT, but human leukocyte antigen (HLA)-1 expression was not upregulated.ConclusionsSCPRT has a substantial immune-stimulatory potential. The importance of the timing of surgery after SCPRT may have been underestimated. An optimal interval for surgery after 5 × 5 Gy may lead to better outcomes, which is possibly exploited in total neoadjuvant therapy schedules using consolidation chemotherapy. Individual patient meta-analyses from appropriate SCPRT trials examining outcomes for each day and prospective trials are needed to clarify the validity of this hypothesis. The interaction of SCPRT with tumour adaptive immunology, in particular the kinetics and timing, should be examined further.     

当归龙荟片联合普芦卡必利治疗慢性功能性便秘的临床研究

目的探讨当归龙荟片联合普芦卡必利治疗慢性功能性便秘的临床疗效。方法选取2018年5月-2019年5月在北京市肛肠医院治疗的慢性功能性便秘患者122例,根据用药的差别分为对照组(61例)和治疗组(61例)。对照组口服琥珀酸普芦卡必利片,2mg/次,1次/d;治疗组在对照组基础上口服当归龙荟片,4片/次,2次/d。两组患者均经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分、PAC-QOL积分、结肠传输试验积分、Bristol和SF-36评分,及血清5-羟色胺(5-HT)、血管活性肠肽(VIP)、P物质(SP)和一氧化氮(NO)水平。结果治疗后,对照组和治疗组临床有效率分别为80.33%和96.72%,两组比较差异具有统计学意义(P<0.05)。经治疗,两组症状积分均明显降低(P<0.05),且治疗组比对照组降低更明显(P<0.05)。经治疗,两组患者PAC-QOL积分和结肠传输试验积分明显降低(P<0.05),而Bristol和SF-36评分明显升高(P<0.05),且治疗组患者明显好于对照组(P<0.05)。经治疗,两组患者血清SP、5-HT水平均显著升高(P<0.05),而VIP和NO水平均明显降低(P<0.05),且治疗组患者SP、5-HT、VIP和NO水平明显优于对照组(P<0.05)。结论当归龙荟片联合普芦卡必利治疗慢性功能性便秘可有效改善患者临床症状,促进患者生活质量改善,具有一定的临床推广应用价值。