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Enhancing antimicrobial stewardship through IT-enabled audits: a quasi-experimental study in urology. 通过it审计加强抗菌药物管理:泌尿学的准实验研究。
Pub Date : 2026-12-02 eCollection Date: 2025-01-01 DOI: 10.1017/ash.2025.10212
Kartik Bhagat, Kavita Diddi, Adel Alsisi, Mohammed Zaqout, Shyam Mohan, Shanmugavalli Ganesan, Jithin Antony, Touseef Sulaimani

Background: Antimicrobial stewardship programs (ASPs) are critical for optimizing antibiotic use and addressing antimicrobial resistance (AMR). Urinary tract infections (UTIs) frequently require antibiotics, yet inappropriate prescribing remains high.

Objective: To assess how a structured audit process, supported by information technology (IT), influences antibiotic prescribing practices for UTIs in the Urology Department at Prime Hospital.

Design: A 12-month quasi-experimental study was conducted in two phases: preintervention and intervention. A customized module in the electronic medical record (EMR) system monitored UTI prescriptions. Alerts for restricted antibiotics were reviewed daily by the antimicrobial stewardship (AMS) team, with immediate feedback to prescribers. The audit emphasized adherence to empirical guidelines, reducing fluoroquinolone use, promoting Access group antibiotics, and minimizing restricted agents.

Patients: All adult UTI patients in the Urology Department were included; pediatric patients under 12 and pregnant women were excluded.

Results: The intervention improved guideline adherence increased the use of Access group antibiotics and reduced restricted antibiotic prescriptions by approximately 50%. Daily multidisciplinary feedback reinforced rational prescribing; however, sustaining long-term behavioral change remained challenging.

Conclusion: Despite growing awareness of AMR, inappropriate antibiotic use persists. IT-enabled audits, combined with multidisciplinary collaboration, effectively enhance guideline adherence, promote rational antibiotic use, and improve patient care outcomes in hospital-based UTI management.

背景:抗菌素管理计划(asp)对于优化抗生素使用和解决抗菌素耐药性(AMR)至关重要。尿路感染(uti)经常需要抗生素,但不适当的处方仍然很高。目的:评估由信息技术(IT)支持的结构化审计过程如何影响主要医院泌尿外科泌尿系统感染的抗生素处方实践。设计:为期12个月的准实验研究,分为干预前和干预两阶段。电子医疗记录(EMR)系统中的定制模块监控尿路感染处方。限用抗生素警报由抗菌素管理(AMS)团队每天审查,并立即反馈给开处方者。审计强调遵守经验性准则,减少氟喹诺酮类药物的使用,推广可及组抗生素,并尽量减少限制药物。患者:纳入泌尿外科所有成年尿路感染患者;12岁以下的儿科患者和孕妇被排除在外。结果:干预提高了指南的依从性,增加了Access组抗生素的使用,并减少了大约50%的限制性抗生素处方。每日多学科反馈强化合理处方;然而,维持长期的行为改变仍然具有挑战性。结论:尽管对抗生素耐药性的认识不断提高,但不适当的抗生素使用仍然存在。信息技术支持的审计与多学科协作相结合,有效地加强了指南的遵守,促进了抗生素的合理使用,并改善了医院UTI管理中的患者护理结果。
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引用次数: 0
Body shape concerns among Jordanian university students: prevalence, correlates, and association with social media use. 约旦大学生对体型的关注:流行程度、相关性以及与社交媒体使用的关系
IF 2.1 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-12-01 Epub Date: 2025-12-12 DOI: 10.1080/20565623.2025.2601632
Hadeel Heilat, Shuja Mashagba, Mosab Said, Ronza Nemrawi, Fadi Alkhawaja, Eman Al-Refai, Mohammad AlElaimat, Saleh Bani Nassr, Dima Oudat

Background: Body shape concerns (BSC) and body dissatisfaction represent emerging public health issues, yet evidence from Middle Eastern contexts, including Jordan, remains limited. These concerns adversely affect psychological health and are shaped by sociocultural pressures and digital media exposure.

Methods: A cross-sectional study was conducted among 418 undergraduate university students in Northern Jordan. Participants completed the Body Shape Questionnaire-8D (BSQ-8D) to assess BSC. Demographic, behavioral, and media use variables were analyzed to identify correlations.

Results: Among 418 respondents (96% aged 17-24; 53% female), 73% reported no BSC. Higher levels of BSC were significantly associated with increased body mass index (BMI) (p < 0.001). Compared to normal-weight peers, overweight students had higher odds of reporting mild [adjusted odds ratio (AOR: 3.7)]and moderate to marked (AOR: 2.56) BSC. Parental education and social media use were also significant factors. Students who did not use Snapchat (AOR = 2.05), did not use TikTok (AOR = 2.15), and cigarette smokers (AOR = 2.75) had higher odds of reporting elevated BSC levels.

Conclusions: BSC among Jordanian university students is shaped by multiple psychosocial and behavioral factors, with BMI emerging as the strongest predictor. Findings underscore the need for culturally informed strategies addressing weight stigma, smoking, parental influences, and media engagement. Integrating BSC screening into routine healthcare may support early detection of at-risk groups.

背景:体型担忧(BSC)和身体不满是新出现的公共卫生问题,但来自中东地区(包括约旦)的证据仍然有限。这些担忧对心理健康产生不利影响,并受到社会文化压力和数字媒体接触的影响。方法:对约旦北部地区418名大学生进行横断面调查。参与者完成身体形状问卷- 8d (BSQ-8D)来评估平衡计分卡。分析人口统计、行为和媒体使用变量以确定相关性。结果:在418名受访者中(96%为17-24岁,53%为女性),73%的人没有记分卡。结论:约旦大学生的平衡记分卡受多种心理社会和行为因素的影响,其中体重指数是最强的预测因子。研究结果强调,需要采取文化知情的策略来解决体重歧视、吸烟、父母影响和媒体参与问题。将BSC筛查纳入常规医疗保健可能有助于早期发现高危人群。
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引用次数: 0
Trpv1-dependent Cacna1b gene inactivation reveals cell-specific functions of CaV2.2 channels in vivo. trpv1依赖性Cacna1b基因失活揭示了体内CaV2.2通道的细胞特异性功能。
IF 3.2 Pub Date : 2026-12-01 Epub Date: 2025-12-22 DOI: 10.1080/19336950.2025.2594893
Remy Y Meir, Martin S Sisti, Arturo Andrade, Diane Lipscombe

Voltage-gated CaV2.2 channels underlie the N-type current, and they regulate calcium entry at many presynaptic nerve endings to control transmitter release. A role for CaV2.2 channels has been well established in the transmission of sensory signals including noxious information using pharmacological and global gene knockout mouse models. However, investigation of the cell-specific actions of CaV2.2 channels has been difficult due to the lack of gene-dependent knockout mouse models and particularly in dissecting behavioral responses that depend on CaV2.2 channel activity. Here, we show the importance of CaV2.2 channels in Trpv1-lineage neurons in behavioral responses to sensory stimuli using Cre-dependent inactivation of the Cacna1b gene. Our work shows the cell-type specificity of CaV2.2 channels in mediating rapidly developing heat hypersensitivity and the utility of Cre-dependent inactivation of Cacna1b to discern cell-specific CaV2.2 channel functions.

电压门控的CaV2.2通道是n型电流的基础,它们调节许多突触前神经末梢的钙进入,以控制递质释放。在药理学和基因敲除小鼠模型中,CaV2.2通道在包括有害信息在内的感觉信号传递中的作用已经得到了很好的证实。然而,由于缺乏基因依赖性敲除小鼠模型,特别是在解剖依赖于CaV2.2通道活性的行为反应方面,对CaV2.2通道的细胞特异性作用的研究一直很困难。在这里,我们通过cre依赖的Cacna1b基因失活,展示了trpv1谱系神经元中CaV2.2通道在对感觉刺激的行为反应中的重要性。我们的研究显示了CaV2.2通道在介导快速发展的热敏反应中的细胞类型特异性,以及cre依赖性Cacna1b失活来识别细胞特异性CaV2.2通道功能的实用性。
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引用次数: 0
One pocket to activate them all (?): Efforts on understanding the modulator pocket in K2P channels. 一个口袋激活他们所有(?):努力理解在K2P信道调制器口袋。
IF 3.2 Pub Date : 2026-12-01 Epub Date: 2025-12-23 DOI: 10.1080/19336950.2025.2602975
Edward Mendez-Otalvaro, Wojciech Kopec, Marcus Schewe, Bert L de Groot

The modulator pocket is a cryptic site discovered in the TREK1 (K2P2.1) K2P channel. This pocket, located close to the selectivity filter, accommodates agonists that enhance the channel's activity. Since its discovery, equivalent sites in other K2P channels have been shown to bind various ligands, both endogenous and exogenous. In this review, we attempt to elucidate how the modulator pocket contributes to K2P channel activation. To this end, we first describe the gating mechanisms reported in the literature and rationalize their modes of action. We then highlight previous experimental and computational evidence for agonists that bind to the modulator pocket, together with mutations at this site that affect gating. Finally, we elaborate how the activation signal arising from the modulator pocket is transduced to the gates in K2P channels. In doing so, we outline a potential common modulator pocket architecture across K2P channels: a largely amphipathic structure - consistent with the expected properties of a pocket exposed at the interface between a hydrophobic membrane and the aqueous solvent - but still with some important channel-sequence-variations. This architecture and its key differences can be leveraged for the design of new selective and potent modulators.

调制器口袋是在TREK1 (K2P2.1) K2P通道中发现的一个神秘位点。这个口袋位于选择性过滤器附近,可容纳增强通道活性的激动剂。自发现以来,其他K2P通道中的等效位点已被证明可以结合各种内源性和外源性配体。在这篇综述中,我们试图阐明调制器口袋如何有助于K2P通道激活。为此,我们首先描述了文献中报道的门控机制,并合理化了它们的作用模式。然后,我们强调了先前的实验和计算证据,表明激动剂结合到调节剂口袋,以及该位点影响门控的突变。最后,我们详细阐述了从调制器口袋产生的激活信号如何被转导到K2P通道中的门。在此过程中,我们概述了一种潜在的跨K2P通道的通用调制器口袋结构:一种很大程度上的两亲结构-与暴露在疏水膜和水性溶剂之间的界面上的口袋的预期性质一致-但仍然存在一些重要的通道序列变化。这种结构及其关键差异可以用于设计新的选择性和有效的调制器。
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引用次数: 0
Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib. 靶向药物lenvatinib毒副作用的系统荟萃分析。
IF 4.3 Pub Date : 2026-12-01 Epub Date: 2025-12-24 DOI: 10.1080/07853890.2025.2598935
Huihui Liu, Kai Wang, Yu Sun, Qingwei Li, Jingfei Shi, Shuai Gao, Chao Cui

Background: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects.

Objective: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis.

Patients/materials and methods: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed.

Results: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001.

Conclusion: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

背景:Lenvatinib是一种治疗多种癌症的有效靶向药物,由于其毒副作用,临床用药安全性受到关注。目的:本研究从九个方面评价lenvatinib诱导的任何不良事件(ae):与循环系统有关的血管毒性(血管毒性、血液系统和心脏)、皮肤及其附属器官的毒性(皮肤/皮下组织和味觉系统)、呼吸系统的毒性(呼吸道、胸腔、纵隔和呼吸道)、神经系统的毒性(神经系统和全身)、消化系统的毒性(胃肠道和肝脏)、泌尿系统的毒性、内分泌和代谢系统的毒性(内分泌和代谢/营养),肌肉骨骼系统的毒性,以及其他严重的毒性。毒副反应按严重程度分为任意级和≥3级进行分析。患者/材料和方法:检索多个数据库,从启动到2024年12月31日,检索lenvatinib癌症临床研究(队列研究和随机对照试验);提取毒副作用数据并进行分析。结果:纳入了9项高质量研究,显示lenvatinib对癌症有效,但有明显的毒性。以高血压为例,对于任何级别,风险比(RR)为2.34,95%可信区间(CI)为[2.09,2.62],z值为14.74,p值为p值。结论:Lenvatinib对癌症有效,但有毒性,本研究支持其临床合理使用。
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引用次数: 0
The molecular mechanism of cuproptosis and research progress in pancreatic diseases. 胰腺疾病中铜增生的分子机制及研究进展。
IF 4.3 Pub Date : 2026-12-01 Epub Date: 2025-12-27 DOI: 10.1080/07853890.2025.2608490
Qizhi Wang, Huijun Chen, Zhen Lv, Peng Zhang, Yingxiao Li, Chuanliang Zhao, Shengqiang Li

Purpose: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases.

Methods: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor.

Results: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis.

Conclusions: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

目的:铜坏死已被证明是一种新的细胞死亡方式,不同于其他类型的细胞死亡,如坏死、铁下垂、焦下垂和细胞凋亡。本文旨在系统综述近年来胰腺疾病中铜质增生的分子机制及其研究进展。方法:通过检索PubMed和Web of Science数据库,纳入113篇重点文献进行专题分析,内容涉及铜增生的分子机制及其在胰腺癌、急慢性胰腺炎、糖尿病、胰腺囊肿、胰腺损伤、胰腺神经内分泌肿瘤发生发展中的作用。结果:cuprotosis是指铜离子在细胞内积累,导致铁蛋白不稳定和酰基化蛋白聚集,导致氧化应激相关的细胞死亡。近年来的研究表明,铜增生在胰腺癌、急慢性胰腺炎、糖尿病、胰腺囊肿、胰腺损伤、胰腺神经内分泌肿瘤等多种胰腺疾病的发生发展中起着重要作用。铜增生的诱导剂,如双硫仑、氯喹诺酮类和紫苏酚类,通过促进细胞铜增生来缓解胰腺癌。铜螯合剂如四乙基苯胺和四硫钼酸盐通过抑制细胞铜还原促进胰腺损伤的恢复。结论:铜倾在胰腺疾病的发病机制中起重要作用。进一步研究铜增生通路可能成为治疗胰腺疾病的潜在靶点。
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引用次数: 0
Zinc status following different bariatric procedures: systematic review and meta-analysis. 不同减肥程序后的锌状态:系统回顾和荟萃分析。
IF 4.3 Pub Date : 2026-12-01 Epub Date: 2025-12-31 DOI: 10.1080/07853890.2025.2608532
Chenglou Zhu, Wenhan Liu

Introduction: This study evaluated perioperative changes in serum zinc levels following different bariatric procedures and provided evidence-based recommendations for postoperative monitoring and supplementation.

Methods: PubMed, Embase, the Cochrane Library, Web of Science and CNKI were systematically searched from inception to July 2025. Eligible studies compared pre- and postoperative serum zinc levels in individuals with obesity undergoing bariatric surgery. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was graded using the GRADE approach. Pooled analyses were conducted with StataSE 17.0.

Results: Twelve studies including 2,529 participants were analysed, with overall quality rated as high. Compared with baseline, pooled standardized mean differences (SMDs) in serum zinc at 3 months, 6 months, 1 year, and 2 years postoperatively were -0.12 (95% CI: -0.27 to 0.04, I2 = 57.9%, τ2 = 0.0265, p = 0.149), -0.36 (95% CI: -0.58 to -0.14, I2 = 82.2%, τ2 = 0.1043, p = 0.001), -0.35 (95% CI: -0.53 to -0.16, I2 = 81.9%, τ2 = 0.0769, p = 0.001), and -0.36 (95% CI: -0.95 to 0.24, I2 = 97.2%, τ2 = 0.3515, p = 0.240), respectively. Subgroup analysis showed no significant changes at 3 months across procedures. However, zinc levels significantly decreased at 6 and 12 months after Roux-en-Y gastric bypass (RYGB) and mini-gastric bypass (MGB), but not after sleeve gastrectomy (SG). At 2 years, no significant reduction was observed in any group. The certainty of evidence for zinc changes was rated as moderate.

Conclusion: Serum zinc levels decline significantly during the first postoperative year, particularly after RYGB and MGB, while SG shows minimal impact. Routine zinc monitoring and individualized supplementation are recommended within the first year after surgery to prevent deficiency-related complications.

Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251138846.

本研究评估了不同减肥手术后围手术期血清锌水平的变化,并为术后监测和补充提供了循证建议。方法:系统检索PubMed、Embase、Cochrane Library、Web of Science和CNKI自建站至2025年7月的文献。符合条件的研究比较了接受减肥手术的肥胖患者术前和术后血清锌水平。使用纽卡斯尔-渥太华量表(NOS)评估研究质量,并使用GRADE方法对证据的确定性进行评分。采用StataSE 17.0进行汇总分析。结果:分析了12项研究,包括2529名参与者,总体质量评价为高。与基线相比,汇集标准化意味着差异(smd)血清锌在3个月、6个月,1年,2年,术后分别为-0.12(95%置信区间CI: -0.27 - 0.04, I2 = 57.9%,τ2 = 0.0265,p = 0.149), -0.36(95%可信区间:-0.58 - -0.14,I2 = 82.2%,τ2 = 0.1043,p = 0.001), -0.35(95%可信区间:-0.53 - -0.16,I2 = 81.9%,τ2 = 0.0769,p = 0.001),和-0.36(95%置信区间CI: -0.95 - 0.24, I2 = 97.2%,τ2 = 0.3515,p = 0.240),分别。亚组分析显示,3个月后,整个治疗过程无显著变化。然而,在Roux-en-Y胃旁路术(RYGB)和迷你胃旁路术(MGB)后6个月和12个月,锌水平显著下降,但在袖胃切除术(SG)后没有显著下降。2年后,在任何组中均未观察到明显的减少。锌变化证据的确定性被评为中等。结论:血清锌水平在术后第一年明显下降,特别是在RYGB和MGB后,而SG的影响很小。建议在手术后一年内进行常规锌监测和个体化补充,以预防缺锌相关并发症。注册:https://www.crd.york.ac.uk/PROSPERO/view/CRD420251138846。
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引用次数: 0
Respiratory-swallow coordination training using bimodal signal biofeedback for patients with post-stroke dysphagia: a randomized controlled trial. 使用双峰信号生物反馈对卒中后吞咽困难患者进行呼吸吞咽协调训练:一项随机对照试验。
IF 4.3 Pub Date : 2026-12-01 Epub Date: 2025-12-29 DOI: 10.1080/07853890.2025.2607218
Lian Wang, Jia Qiao, Zhenhai Wei, Xiaoqin Liu, Xiaomei Wei, Zulin Dou

Objective: The purpose was to investigate the effects of respiratory-swallow coordination training with bimodal signal biofeedback on swallowing function in patients with post-stroke dysphagia.

Methods: Post-stroke dysphagia Patients were randomly assigned to either the control group or the experimental group. The control group received conventional rehabilitation, while the experimental group underwent additional respiratory-swallow coordination training based on biofeedback. The training protocol consisted of three phases, conducted at an intensity of 30 min/day, 6 days/week, for two consecutive weeks. Outcome measures included the Functional Oral Intake Scale (FOIS) score, the Rosenbek Penetration-Aspiration Scale (PAS) score, respiratory-swallow coordination, and videofluoroscopic swallowing study temporal and kinematic parameter. Assessments were conducted at baseline, post-treatment, and at a one-month follow-up.

Results: Thirty patients were enrolled. Both groups showed significant improvement in FOIS scores from baseline to both two-week post-treatment and one-month follow-up (p < 0.001). Compared to the controls, the experimental group demonstrated significantly greater FOIS scoreimprovement at both post-treatment and follow-up (p < 0.001). The proportion of patients with a ≥ 2-point increase in FOIS scores was significantly higher in the experimental group than in the control group at both post-treatment (p < 0.01) and one-month follow-up (p < 0.01). After two weeks of treatment, the percentage of PAS scores ≥6 was significantly lower in the experimental group than in the control group (p < 0.001). Additionally, the percentage of optimal respiratory-swallow pattern was significantly higher in the experimental group than in the control group (p < 0.001).

Conclusion: Bimodal signal biofeedback-based respiratory-swallow coordination training can effectively improve respiratory-swallow coordination and swallowing function in patients with post-stroke dysphagia.

目的:探讨双峰信号生物反馈呼吸-吞咽协调训练对脑卒中后吞咽困难患者吞咽功能的影响。方法:将脑卒中后吞咽困难患者随机分为对照组和实验组。对照组接受常规康复治疗,实验组接受基于生物反馈的呼吸吞咽协调训练。训练方案包括三个阶段,以30分钟/天的强度进行,每周6天,连续两周。结果测量包括功能性口服摄入量表(FOIS)评分、Rosenbek渗透-吸入量表(PAS)评分、呼吸-吞咽协调、透视吞咽研究时间和运动学参数。评估分别在基线、治疗后和1个月随访时进行。结果:30例患者入组。两组患者在治疗后2周及随访1个月FOIS评分均有显著改善(p p),试验组治疗后FOIS评分≥2分的提高均显著高于对照组(p p p p)。结论:基于双峰信号生物反馈的呼吸吞咽协调训练可有效改善脑卒中后吞咽困难患者的呼吸吞咽协调和吞咽功能。
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引用次数: 0
Proband-independent noninvasive prenatal diagnosis for spinal muscular atrophy: early detection paving the way for early prenatal treatment. 脊髓性肌萎缩症的无创产前诊断:早期发现为早期产前治疗铺平道路。
IF 4.3 Pub Date : 2026-12-01 Epub Date: 2026-01-05 DOI: 10.1080/07853890.2025.2610892
Huanyun Li, Shanshan Gao, Shaojun Li, Zhenhua Zhao, Xinyu Fu, Jingqi Zhu, Jun Feng, Weiqin Tang, Di Wu, Xiangdong Kong

Background: To validate the clinical efficacy of non-invasive prenatal diagnosis (NIPD) for spinal muscular atrophy (SMA) in the first trimester and extend its applicability to families without probands.

Method: From December 2020 to October 2024, 288 high-risk pregnancies were recruited prospectively, with 81 qualifying for NIPD after genetic counseling. Among the eligible cases, parent-based haplotypes were successfully constructed in 75 families (92.6%), while grandparent-based haplotype reconstruction was performed for the remaining 6 cases (7.4%) where proband samples were unavailable. Through targeted sequencing of the SMN1/SMN2 gene and flanking informative SNPs in maternal plasma, fetal haplotypes were inferred by analyzing dosage changes in cell-free DNA (cfDNA) using Bayes factor. All NIPD results were subsequently validated through invasive diagnostic procedures (chorionic villus sampling or amniocentesis).

Results: The haplotypes were successfully constructed in 81 families through parents or grandparents of the identified variant carriers. 76 families (93.8%) successfully obtained NIPD results, among which the earliest gestational week for successful NIPD was 7+3 weeks, with a minimum fetal fraction of 1.9%. 5 cases were classified 'no call' results due to pathogenic variant-adjacent recombination events (2/5), insufficient or unevenly distributed informative SNPs (2/5), and subthreshold fetal fraction (1/5). The average gestational age of NIPD blood drawing is 9 weeks. Validation test showed the NIPD results accuracy was 100%.

Conclusion: This study demonstrates the clinical feasibility of grandparent-assisted haplotype construction for SMA families without probands and enables accurate early prenatal diagnosis of SMA in first-trimester pregnancies.

背景:验证无创产前诊断(NIPD)对妊娠早期脊髓性肌萎缩症(SMA)的临床疗效,并将其应用于无先证家庭。方法:从2020年12月至2024年10月,前瞻性招募高危孕妇288例,其中81例经遗传咨询符合NIPD。在符合条件的病例中,75例(92.6%)成功构建了基于父母的单倍型,其余6例(7.4%)未获得先证样本的家庭进行了基于祖父母的单倍型重建。通过对母体血浆中SMN1/SMN2基因和侧翼信息性snp的靶向测序,利用贝叶斯因子分析游离DNA (cfDNA)的剂量变化推断胎儿单倍型。所有NIPD结果随后通过侵入性诊断程序(绒毛膜绒毛取样或羊膜穿刺术)进行验证。结果:通过鉴定的变异携带者的父母或祖父母成功构建了81个家系的单倍型。76个家庭(93.8%)成功获得NIPD结果,其中成功NIPD的最早妊娠周为7+3周,最低胎率为1.9%。5例因致病变异邻近重组事件(2/5)、信息性snp不充分或分布不均匀(2/5)和胎儿分数低于阈值(1/5)而被分类为“no call”结果。NIPD抽血的平均胎龄为9周。验证试验表明,NIPD结果的准确度为100%。结论:本研究为无先证的SMA家族进行祖父母辅助单倍型构建的临床可行性提供了依据,为早期妊娠SMA的产前准确诊断提供了依据。
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引用次数: 0
Clinical impact of disease stability on exacerbation and mortality in COPD: a retrospective cohort study. 疾病稳定性对慢性阻塞性肺病加重和死亡率的临床影响:一项回顾性队列研究
IF 4.3 Pub Date : 2026-12-01 Epub Date: 2026-01-05 DOI: 10.1080/07853890.2025.2611466
Sang Hyuk Kim, Jung-Kyu Lee, Kyung Hoon Min, Deog Kyeom Kim, Hyun Woo Lee

Background: Disease stability is an achievable goal in chronic obstructive pulmonary disease (COPD) management. However, the clinical implications of disease stability in patients with COPD remain unclear.

Methods: We conducted a single-center retrospective cohort study using the electronic medical records of treated patients with symptomatic COPD. Patients who had newly initiated inhaler therapy with long-acting β2-agonist/long-acting muscarinic antagonist (LABA/LAMA) or inhaled corticosteroid/LABA/LAMA combinations were included. Disease stability was defined over a one-year assessment period as meeting all of the following criteria: (1) symptom stability; (2) no moderate or severe exacerbations; and (3) no rapid decline in lung function. The outcomes included acute exacerbations and all-cause mortality.

Results: Of the 725 screened patients, 405 were eligible for inclusion in the study. Among them, 158 (39.0%) achieved disease stability. The proportions of patients who met each criterion were 70.4% for symptom stability, 63.7% for no exacerbations, and 71.4% for a non-rapid lung function decline. Only 5.9% met none of these criteria. During the follow up duration of median 62 (interquartile ranges, 30-90) months, disease stability was significantly associated with a reduced risk of moderate-to-severe (adjusted hazard ratio [aHR] 0.521, 95% confidence interval [CI] 0.392-0.692) and severe (aHR 0.393, 95% CI 0.279-0.553) exacerbations after adjusting for confounders. It was also associated with a decreased mortality risk (aHR 0.345, 95% CI 0.135-0.883).

Conclusion: Disease stability was associated with a lower risk of exacerbation and mortality, suggesting its potential role as a treatment target and outcome measure for COPD.

背景:疾病稳定性是慢性阻塞性肺疾病(COPD)治疗中可实现的目标。然而,COPD患者疾病稳定性的临床意义尚不清楚。方法:我们进行了一项单中心回顾性队列研究,使用治疗的有症状的COPD患者的电子病历。新开始使用长效β2激动剂/长效毒蕈碱拮抗剂(LABA/LAMA)或吸入皮质类固醇/LABA/LAMA联合吸入治疗的患者被纳入研究。在一年的评估期内,疾病稳定性被定义为满足以下所有标准:(1)症状稳定;(2)无中度或者重度加重;(3)肺功能无快速下降。结果包括急性加重和全因死亡率。结果:在725例筛选的患者中,405例符合纳入研究的条件。其中158例(39.0%)达到疾病稳定。符合各项标准的患者比例为症状稳定70.4%,无加重63.7%,肺功能非快速下降71.4%。只有5.9%的人不符合这些标准。在中位随访62个月(四分位数间距30-90个月)期间,经混杂因素校正后,疾病稳定性与中度至重度(校正风险比[aHR] 0.521, 95%可信区间[CI] 0.392-0.692)和重度(aHR 0.393, 95%可信区间[CI] 0.79% -0.553)恶化风险降低显著相关。它还与死亡风险降低相关(aHR 0.345, 95% CI 0.135-0.883)。结论:疾病稳定性与较低的恶化风险和死亡率相关,提示其作为COPD治疗靶点和结局指标的潜在作用。
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