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.     

Hip Displacement in Cerebral Palsy: The Role of Surveillance

IntroductionHip displacement is common in cerebral palsy (CP) and is related to the severity of neurological and functional impairment. It is a silent, but progressive disease, and can result in significant morbidity and decreased quality of life, if left untreated. The pathophysiology of hip displacement in CP is a combination of hip flexor-adductor muscle spasticity, abductor muscle weakness, and delayed weight-bearing, resulting in proximal femoral deformities and progressive acetabular dysplasia. Due to a lack of symptoms in the early stages of hip displacement, the diagnosis is easily missed. Awareness of this condition and regular surveillance by clinical examination and serial radiographs of the hips are the key to early diagnosis and treatment.Hip surveillance programmesSeveral population-based studies from around the world have demonstrated that universal hip surveillance in children with CP allows early detection of hip displacement and appropriate early intervention, with a resultant decrease in painful dislocations. Global hip surveillance models are based upon the patients’ age, functional level determined by the Gross Motor Function Classification system (GMFCS), gait classification, standardized clinical exam, and radiographic indices such as the migration percentage (MP), as critical indicators of progressive hip displacement.ConclusionDespite 25 years of evidence showing the efficacy of established hip surveillance programmes, there is poor awareness among healthcare professionals in India about the importance of regular hip surveillance in children with CP. There is a need for professional organizations to develop evidence-based guidelines for hip surveillance which are relevant to the Indian context.     

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。