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Tourniquets have been modified and used for centuries to occlude blood flow to control hemorrhage. More recently, the occlusion of peripheral vessels has been linked to resultant increases in blood pressure, which may provide additional therapeutic potential, particularly during states of low cardiac output.The objective of this study was to investigate a causal relationship between tourniquet application and blood pressure in healthy adults.Healthy adult volunteers were recruited to participate in this IRB-approved study. Each participant met inclusion criteria and demonstrated baseline normotension. Brachial cuff blood pressure and heart rate were recorded pre- and post-tourniquet application to the bilateral legs.Twenty-seven adults aged 22 to 35 years participated and were included in analysis. The average systolic blood pressure was 122 ± 7 mmHg, diastolic blood pressure was 72 ± 9 mmHg, and heart rate was 70 ± 13 bpm. Following bilateral tourniquet application over the femoral vasculature, we observed a statistically significant increase in systolic (7 mmHg, p0.001) and diastolic (4 mmHg, p = 0.05) blood pressures with no significant change in heart rate (2 bpm, p0.05).The elevations in systolic and diastolic blood pressures establish a dependent relationship between tourniquet application to the lower extremities and blood pressure elevation. These results may support new indications for tourniquet-use or extremity vessel occlusion in settings of hemodynamic instability.

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC. ispartof: CANCER vol:129 issue:5 pages:697-713 ispartof: location:United States status: published

PURPOSE OF REVIEW: Shoulder instability in patients with underlying joint hyperlaxity can be challenging to treat. Poorly defined terminology, heterogeneous treatments, and sparse reports on clinical outcomes impair the development of best practices in this patient population. This article provides a review of the current literature regarding optimal management of patients suffering from shoulder instability with concomitant hyperlaxity of the shoulder, from isolated shoulder joint hyperlaxity to congenital hypermobility spectrum disorders (HSD). RECENT FINDINGS: Current research shows specialized physiotherapy protocols focused on strengthening of periscapular muscles and improvement of sensorimotor control are a promising non-surgical therapeutic avenue in certain patients, which can be augmented by device-based intervention in select cases. If surgical treatment is warranted, arthroscopic techniques such as pancapsular shift or plication continue to demonstrate favorable outcomes and are currently considered the benchmark for success. The long-term success of more recent innovations such as coracoid process transfers, conjoint tendon transfers, subscapularis tendon augmentation, and capsular reconstruction remains unproven. For patients affected by connective tissue disorders, treatment success is generally less predictable, and the entire array of non-operative and operative interventions needs to be considered to achieve the best patient-specific treatment results. SUMMARY: In the treatment of shoulder instability and concomitant hyperlaxity, specialized physiotherapy protocols augmented by device-based interventions have emerged as powerful, non-operative treatment options for select patients. Successful surgical approaches have been demonstrated to comprehensively address capsular redundancy, labral lesions, and incompetence of additional passive stabilizers in a patient-specific fashion, respective of the underlying connective tissue constitution.

CD8 virtual memory T (TVM) cells are Ag-naive CD8 T cells that have undergone partial differentiation in response to common γ-chain cytokines, particularly IL-15 and IL-4. TVM cells from young individuals are highly proliferative in response to TCR and cytokine stimulation but, with age, they lose TCR-mediated proliferative capacity and exhibit hallmarks of senescence. Helminth infection can drive an increase in TVM cells, which is associated with improved pathogen clearance during subsequent infectious challenge in young mice. Given the cytokine-dependent profile of TVM cells and their age-associated dysfunction, we traced proliferative and functional changes in TVM cells, compared with true naive CD8 T cells, after helminth infection of young and aged C57BL/6 mice. We show that IL-15 is essential for the helminth-induced increase in TVM cells, which is driven only by proliferation of existing TVM cells, with negligible contribution from true naive cell differentiation. Additionally, TVM cells showed the greatest proliferation in response to helminth infection and IL-15 compared with other CD8 T cells. Furthermore, TVM cells from aged mice did not undergo expansion after helminth infection due to both TVM cell–intrinsic and –extrinsic changes associated with aging.

For decades, the three-digit United States Medical Licensing Exam Step 1 score has been used to competitively evaluate and compare candidates during the residency application process. Starting in 2022, however, all Step 1 scores will be converted to pass/fail. A different quantitative measure will likely gain importance in its stead, one such being clerkship performance grades. This study aims to determine the consistency of class rank and distribution of clerkship grades reported by medical schools for applicants to a general surgery program.Candidates' Medical Student Performance Evaluation letters from 141 unique US allopathic medical schools were reviewed for student overall class rank, the number of grading tiers in each clerkship, and the percent achieving honors criteria in each clerkship from the 2020 application cycle. Comparative analysis was performed by region and medical school prestige.Most medical schools rank students using a four-tier system (e.g., fail, pass, high pass, and honors). A third of schools do not provide an overall class rank of students (34.7% of schools); this was most prevalent in the Northeast and Western regions. Schools in the Central US more often rank their students in five tiers compared to the South (P 0.01). The percent of students that achieve the highest grading tier varies across the core clerkships (mean 37.1%, range 6.5%-78%); an average of 34.5% of students meet the highest honors tier in their Surgery clerkship. Students at US News and World Report Top 20 medical schools are more likely to receive the highest honors tier, across all core clerkships and overall class rank, than students at schools outside the Top 20 (P 0.05).In the absence of the United States Medical Licensing Exam Step 1 score, the variability in clerkship grading tiers and overall class rank will likely pose a challenge to residency programs' ability to stratify desirable applicants. Further transparency and standardization may be required to compare students objectively and fairly from medical schools across the country.

Many studies have sought to explore the impact of high-dose gonadotropin on stimulation outcomes based on a hypothesis that higher doses of follicle-stimulating hormone may harm the quantity or quality of oocytes and, therefore, be counterproductive. Herein, we describe the results of a narrative review aimed at elucidating any harm associated with "excess" follicle-stimulating hormone dosing in poor-to-moderate responders. Additionally, we sought to describe the outcomes associated with mild ovarian stimulation, with an eye toward determining whether this approach is superior. We concluded that there is no apparent harm to higher-dose gonadotropin stimulation for poor-to-moderate responders. Simultaneously, we did not find compelling data to suggest that mild stimulation is superior. Finally, we close by presenting data that suggest that more gonadotropin may be beneficial in specific clinical scenarios.

Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.