Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T₂-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T₂-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T₂-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T₂ relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T₂ was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T₂ relaxation time was derived (R² = 0.98): T₂ (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T₂-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T₂-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.     

Midterm Outcomes of Angioplasty for Pediatric Renovascular Hypertension

PurposeTo evaluate the midterm outcomes of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH).Materials and MethodsThe clinical data of patients who underwent PTRA for RVH in the authors’ hospital from 2012 to 2019 were retrospectively analyzed. Postprocedural blood pressure, glomerular filtration rate (GFR) of the affected kidney, restenosis, and complications were closely monitored.ResultsPTRA was performed in a total of 30 children (20 boys and 10 girls), with a mean age of 7.3 years ± 0.7 (range, 40 days to 13.9 years) and a mean weight of 25.0 kg ± 2.3 (range, 3.4–53 kg). The median follow-up period was 26.5 months (range, 1 month to 7.5 years). Technical success was achieved in 26 (86.7%) of the 30 patients. Restenosis developed in 3 patients (10.0%). Only 1 patient underwent stent implantation, and the stent fractured 8 months later, requiring further intervention. There were no other complications. In terms of clinical benefit of blood pressure control after the initial PTRA procedure, 15 patients (50%) were cured and 7 patients (23.3%) showed improvement. There was no significant difference in the etiology, lesion location, and lesion length between patients with clinical benefit and failure (P = .06, P = .202, and P = .06, respectively). GFR of the affected kidney was significantly improved from 19.9 mL/min ± 11.2 to 38.1 mL/min ± 11.9 at the 6-month follow-up after PTRA (P < .001).ConclusionsThe overall results of PTRA for pediatric RVH caused by different etiologies are promising. PTRA not only provided a clinical benefit of blood pressure control in 73.3% of the patients but also significantly improved the function of the affected kidney.     

李延应用泽泻汤合温胆汤治疗舒张压高的临床经验

随着社会的发展,人类生活方式的改变,高血压病越来越高发,具有低龄化趋势,代谢综合征常伴随发生,此种情况下的高血压往往是以舒张压升高为主,临床表现常与“亚健康”状态混淆,未能引起患者甚至部分医生的重视,然而事实上越来越多的科学研究证实舒张压高之危害十分明显,不容忽视。尽管现代医学对舒张压高的病因及病理机制有明确的阐述,但是暂时没有特效的药物。李延教授在治疗高血压病方面有着丰富的临床经验,临床中运用泽泻汤合温胆汤加减治疗舒张压高之眩晕,切中病机,加减灵活,屡有良效。文中从中医角度阐述舒张压高的病因病机,介绍李师辨病辨证思路,组方用药特点,附三则典型验案,另加个人心得体会,以期为舒张压高的有效治疗提供思路。     

2013-2017年我国四种恶性肿瘤住院费用水平及结构变动度分析

背景　恶性肿瘤给家庭、社会带来了沉重的医疗、经济负担，极易导致部分家庭“因病致贫”或放弃治疗，目前相关研究多集中于单一病种、分散地域的研究，仍缺乏对于全国范围与多病种恶性肿瘤住院费用变化及结构构成的考量。目的　分析2013-2017年我国4种恶性肿瘤住院费用水平以及影响住院费用的主要项目和结构变动情况，为控制医疗费用上涨、深化新医改提供参考依据。方法　本研究数据来源于《2014中国卫生和计划生育统计年鉴》《2015中国卫生和计划生育统计年鉴》《2016中国卫生和计划生育统计年鉴》《2017中国卫生和计划生育统计年鉴》以及《2018中国卫生健康统计年鉴》，样本跨度为2013-2017年。统计“30种疾病人均住院费用”中的胃恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤以及膀胱恶性肿瘤的数据，4种恶性肿瘤的人均住院费用包括药费、检查费、治疗费、手术费和手术材料费。2019年4-8月，采用结构变动度法分析我国2013-2017年4种恶性肿瘤的住院费用的结构变动情况〔结构变动值（VSV）、结构变动度（DSV）、结构变动贡献率〕。结果　2013-2017年，4种恶性肿瘤的人均住院费用逐年上升，其中胃恶性肿瘤的人均住院费用始终最高，且肺恶性肿瘤的人均住院费用上升幅度最大。2013-2017年，在4种恶性肿瘤住院各项费用的占比中，药费占比最高且总体逐年下降。从4种恶性肿瘤住院各项费用的实际变化来看，药费在2013-2014年有所上升，2014-2017年逐年下降；检查费在2013-2014年下降，2014-2017年缓慢上升；手术费与手术材料费在2013-2017年逐年上升。2013-2017年，在4种恶性肿瘤住院各项费用中均是药费的VSV最大；4种恶性肿瘤药费、检查费的VSV均呈负向变化，手术费和手术材料费的VSV均呈正向变化，治疗费的VSV增减均不明显。2013-2017年，4种恶性肿瘤住院费用的DSV从大到小依次为肺恶性肿瘤、胃恶性肿瘤、食管恶性肿瘤、膀胱恶性肿瘤。2013-2017年，4种恶性肿瘤住院各项费用中均是药费的结构变动贡献率最大，治疗费的结构变动贡献率最小；除药费外，胃恶性肿瘤、肺恶性肿瘤住院各项费用中均是手术材料费和手术费的结构变动贡献率次之，食管恶性肿瘤住院各项费用中手术费、检查费的结构变动贡献率次之，膀胱恶性肿瘤住院各项费用中检查费、手术材料费的结构变动贡献率次之。结论　2013-2017年我国4种恶性肿瘤手术费的结构变动贡献率虽然较为理想，但药费、治疗费仍是住院费用结构的重点调整对象；同时为有效降低恶性肿瘤的人均住院费用，应当加强控制手术材料费与检查费；而胃恶性肿瘤与肺恶性肿瘤患者的疾病经济负担严重，若要缓解应加强疾病的早期预防与住院费用管控。