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.     

主动脉出口血压对左心室血流特性的影响

采用Mimics对心脏进行三维重构，用3-matic进行模型优化以及模型误差分析，对左心室室壁运动做速度分布假设，基于UDF宏文件对左心室室壁运动编写程序，将血液视为非牛顿流体，采用动网格技术研究不同血压对左心室血液流动的影响。模拟发现当左心室收缩时，压力梯度明显，内部压力减小。当左心室舒张时，内部压力逐渐增高。二尖瓣口处的速率先增大后减小。血压升高，左心室内剪切应力持续增大，极易破坏红细胞结构，产生溶血现象，导致心脏功能紊乱。     

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.     

Prior surgical fixation of proximal humerus fractures is associated with increased complications following subsequent reverse shoulder arthroplasty

BackgroundThe objective of this study was to compare complication rates between patients undergoing reverse shoulder arthroplasty (RSA) after a prior open reduction and internal fixation (ORIF) for proximal humerus fracture (PHF) to those undergoing RSA as a primary treatment for PHFs, glenohumeral osteoarthritis, or rotator cuff tear arthropathy (CTA).MethodsPatients who underwent RSA between 2015 and 2020 were identified in the Mariner database. Patients were separated into 3 mutually exclusive groups: (1) RSA for osteoarthritis, rotator cuff tear, or CTA (Control-RSA); (2) RSA as a primary treatment for PHF (PHF-RSA); and (3) RSA for patients with prior ORIF of PHFs (ORIF-RSA). Ninety-day medical and 2-year postoperative surgical complications were identified. In addition, patients in the PHF-RSA group were subdivided into those undergoing RSA for PHF within 3 months of the fracture (acute) vs. those treated greater than 3 months from diagnosis (delayed). Multivariate regression was performed to control for differences in comorbidities and demographics.ResultsA total of 30,824 patients underwent primary RSA for arthritis or CTA, 5389 patients underwent RSA as a primary treatment for a PHF, and 361 patients underwent RSA after ORIF of a PHF. ORIF before RSA was associated with an increased risk of overall revision (odds ratio [OR] 2.45, P = .002), infection (OR 2.40, P < .001), instability (OR 2.43, P < .001), fracture (OR 3.24, P = .001), minor medical complications (OR 1.59, P = .008), and readmission (OR 2.55, P = .001) compared with the Control-RSA cohort. RSA as a primary treatment for PHF was associated with an increased risk of 2-year revision (OR 1.60, P < .001), infection (OR 1.51, P < .001), instability (OR 2.84, P < .001), and fracture (OR 2.54, P < .001) in addition to major medical complications (OR 2.02, P < .001), minor medical complications (OR 1.92, P < .001), 90-day emergency department visits (OR 1.26, P < .001) and 90-day readmission (OR 2.03, P < .001) compared with the Control-RSA cohort. The ORIF-RSA group had an increased risk of periprosthetic infection (OR 1.94, P = .002) when compared with the PHF-RSA cohort. There were no differences in medical or surgical complications in the RSA-PHF cohort between patients treated in an acute or delayed fashion.ConclusionRSA following ORIF of a PHF is associated with increased complications compared with patients undergoing RSA for nonfracture indications. Prior ORIF of a PHF is also an independent risk factor for postoperative infection after RSA compared with patients who undergo RSA as a primary operation for fracture. The timing of RSA as a primary operation for PHF does not appear to impact the rates of postoperative medical and surgical complications.