Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Moving Knowledge to Action: Aware,Adopt, Adapt (A3)

This article begins with an overview of the knowledge translation (KT) process, introduces commonly used KT terms and the Aware-Adopt-Adapt (A³) KT map. The A³ was created by a nurse practitioner (NP) for practitioners and NP students to provide a map for those who wish to move existing knowledge to practice, yet do not know where to start or do not have the time to take a deeper dive into specific KT theories.     

糖尿病前期中医证型及证素特点分析＊

目的 探讨糖尿病前期的中医证型及证素分布特点。方法 检索中国知网、万方及维普三大数据库中收录的自建库以来有关糖尿病前期证型的临床研究文献，对中医证型进行规范整理，建立数据库，提取证素，运用数据挖掘技术中的关联分析、聚类分析探究证素分布规律。结果 共纳入10篇文献，总有效病例1620例，证型经规范处理后整理为18个，主要证型为脾虚痰湿证。共提取证素13个，主要病位证素为脾，主要病性证素为气虚、湿和痰，关联分析显示脾—湿支持度和置信度最高，聚类分析结果可得到3个聚类组。结论 糖尿病前期病位在脾，气虚、脾、痰、湿是常见证素，临床诊治糖尿病前期应注重从脾论治，需辨证施治。     

Egg Intake Has No Adverse Association With Blood Lipids Or Glucose In Adolescent Girls

Objective: Longitudinal data on cardiometabolic effects of egg intake during adolescence are lacking. The current analyses aim to evaluate the impact of usual adolescent egg consumption on lipid levels, fasting glucose, and insulin resistance during late adolescence (age 17–20?years).

Methods: Data from 1392 girls, aged 9 to 10 at baseline and followed for 10?years, in the National Heart, Lung, and Blood Institute’s National Growth and Health Study were used to examine the association between usual egg intake alone and in combination with other healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and insulin resistance, measured as homeostasis model assessment of insulin resistance (HOMA-IR). Diet was assessed using 3-day food records during eight examination cycles. Girls were classified according to usual weekly egg intake, ages 9–17?years:?<1 egg/wk (n?=?361), 1 to <3 eggs/wk (n?=?703), and ≥3 eggs/wk (n?=?328). Analysis of covariance modeling was used to control for confounding by other behavioral and biological risk factors.

Results: Girls with low, moderate, and high egg intakes had adjusted low-density lipoprotein cholesterol levels of 99.7, 98.8, and 95.5 mg/dL, respectively (p?=?0.0778). In combination with higher intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were stronger and statistically significant. There was no evidence that ≥3 eggs/wk had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who consumed ≥3 eggs/wk had the lowest levels of insulin resistance.

Conclusion: These results suggest that eggs may be included as part of a healthy adolescent diet without adverse effects on glucose, lipid levels, or insulin resistance.     

Adaptation of Vero cells to suspension growth for rabies virus production in different serum free media

Vero cells are nowadays widely used in the production of human vaccines. They are considered as one of the most productive and flexible continuous cell lines available for vaccine manufacturing. However, these cells are anchorage dependent, which greatly complicates upstream processing and process scale-up. Moreover, there is a recognized need to reduce the costs of vaccine manufacturing to develop vaccines that are affordable worldwide. The use of cell lines adapted to suspension growth contributes to reach this objective.The current work describes the adaptation of Vero cells to suspension culture in different serum free media according to multiple protocols based on subsequent passages. The best one that relies on cell adaption to IPT-AFM an in-house developed animal component free medium was then chosen for further studies. Besides, as aggregates have been observed, the improvement of IPT-AFM composition and mechanical dissociation were also investigated.In addition to IPT-AFM, three chemically defined media (CD293, Hycell CHO and CD-U5) and two serum free media (293SFMII and SFM4CHO) were tested to set up a serum free culture of the suspension-adapted Vero cells (VeroS) in shake flasks. Cell density levels higher than 2 × 10⁶ cells/mL were obtained in the assessed conditions. The results were comparable to those obtained in spinner culture of adherent Vero cells grown on Cytodex 1 microcarriers.Cell infection with LP-2061 rabies virus strain at an MOI (Multiplicity of Infection) of 0.1 and a cell density of 8 ± 0.5 × 10⁵ cells/mL resulted in a virus titer higher than 10⁷ FFU/mL in all media tested. Nevertheless, the highest titer equal to 5.2 ± 0.5 × 10⁷ FFU/mL, was achieved in IPT-AFM containing a reduced amount of Ca⁺⁺ and Mg⁺⁺. Our results demonstrate the suitability of the obtained VeroS cells to produce rabies virus at a high titer, and pave the way to develop VeroS cells bioreactor process for rabies vaccine production.     

Anatomic vs. reverse shoulder arthroplasty for glenohumeral osteoarthritis with intact rotator cuff: a retrospective comparison of patient-reported outcomes using the systems outcomes database with up to 5-year follow-up

BackgroundThe growing enthusiasm for the use of reverse shoulder arthroplasty (RSA) in the treatment of primary glenohumeral osteoarthritis (GHOA) with an intact rotator cuff is based on data derived from single-center studies with limited generalizability and follow-up. This study compared patient-reported outcomes (PROs) between RSA and total shoulder arthroplasty (TSA) for the treatment of primary GHOA with up to 5-year follow-up and examined temporal trends in the treatment of GHOA between 2012 and 2021.MethodsA retrospective review was performed on patients with primary GHOA undergoing primary arthroplasty surgery from the Surgical Outcomes System global registry between 2012 and 2021. PROs including the American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, and visual analog scale (VAS) for pain were compared between RSA and TSA at 1, 2, and 5 years postoperatively.ResultsA total of 4451 patients were included, with 2693 (60.5%) undergoing TSA and 1758 (39.5%) undergoing RSA. Both RSA and TSA provided clinically excellent outcomes at 1 year postoperatively (ASES: 80.8 ± 17.9 vs. 85.9 ± 15.2, respectively; SANE: 74.8 ± 24.7 vs. 79.5 ± 22.9; VAS pain: 1.3 ± 2.0 vs. 1.1 ± 1.7; all P < .05) that were maintained at 2 years (ASES: 81.3 ± 19.3 vs. 87.3 ± 14.9; SANE: 74.8 ± 26.2 vs. 79.7 ± 24.7; VAS pain: 1.3 ± 2.1 vs. 1.0 ± 1.6; all P < .05) and 5 years (ASES: 81.7 ± 16.5 vs. 86.9 ± 15.3; SANE: 71.6 ± 28.5 vs. 78.2 ± 25.9; VAS pain: 1.0 ± 1.7 vs. 1.0 ± 1.7; all P < .05), with statistical significance favoring TSA. After controlling for age and sex, there was an adjusted difference of 4.5 units in the ASES score favoring TSA (P = .005) at 5 years postoperatively but no differences in adjusted SANE (P = .745) and VAS pain (P = .332) scores. The use of RSA for GHOA grew considerably over time, from representing only 17% of all replacements performed for GHOA in 2012 to nearly half (47%) in 2021 (P < .001).ConclusionRSA as a treatment for GHOA with an intact rotator cuff seems to yield PROs that are largely clinically equivalent to TSA extending to 5 years postoperatively. The observed statistical significance favoring TSA appears to be of marginal clinical benefit based on established minimal clinically important differences and may be a result of the large sample size. Further research using more granular clinical data and examining differences in range of motion and complications is warranted as it may change the value analysis.     

Esophageal Surveillance Practices in Esophageal Atresia Patients: A Survey by the Eastern Pediatric Surgery Network

IntroductionEndoscopic surveillance guidelines for patients with repaired esophageal atresia (EA) rely primarily on expert opinion. Prior to embarking on a prospective EA surveillance registry, we sought to understand EA surveillance practices within the Eastern Pediatric Surgery Network (EPSN).MethodsAn anonymous, 23-question Qualtrics survey was emailed to 181 physicians (surgeons and gastroenterologists) at 19 member institutions. Likert scale questions gauged agreement with international EA surveillance guideline-derived statements. Multiple-choice questions assessed individual and institutional practices.ResultsThe response rate was 77%. Most respondents (80%) strongly agree or agree that EA surveillance endoscopy should follow a set schedule, while only 36% claimed to perform routine upper GI endoscopy regardless of symptoms. Many institutions (77%) have an aerodigestive clinic, even if some lack a multi-disciplinary EA team. Most physicians (72%) expressed strong interest in helping develop evidence-based guidelines.ConclusionsOur survey reveals physician agreement with current guidelines but weak adherence. Surveillance methods vary greatly, underscoring the lack of evidence-based data to guide EA care. Aerodigestive clinics may help implement surveillance schedules. Respondents support evidence-based protocols, which bodes well for care standardization. Results will inform the first multi-institutional EA databases in the United States (US), which will be essential for evidence-based care.Level of EvidenceThis is a prognosis study with level 4 evidence.