Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

双环[1.1.1]戊烷衍生物的合成研究进展

双环[1.1.1]戊烷（BCP）是一种具有三维立体结构的桥环骨架，其作为苯环、叔丁基和炔烃的生物电子等排体，已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大，BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结，旨在为新药研发人员提供参考。     

2例胰岛素自身免疫综合征临床病例分析

通过回顾分析我院2例确诊为胰岛素自身免疫综合征(IAS)患者的临床资料,并复习相关文献,总结发病机制及治疗方法,探讨IAS患者的临床特点,提高对低血糖症的诊治水平。     

Factors associated with provision of depot medroxyprogesterone acetate to adolescents by US health care providers

ObjectiveIdentify factors associated with healthcare providers' frequency of depot medroxyprogesterone acetate (DMPA) provision to adolescents.Study designWe analyzed data from surveys mailed to a nationally representative sample of public-sector providers and office-based physicians (n=1984). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with frequent DMPA provision to adolescents in the past year.ResultsAlthough most providers (>95%) considered DMPA safe for adolescents, fewer reported frequent provision (89% of public-sector providers; 64% of office-based physicians). Among public-sector providers, factors associated with lower odds of frequent provision included working in settings without Title X funding (aOR 0.44, 95% CI 0.30–0.64), reporting primary care as their primary clinical focus versus reproductive or adolescent health (aOR 0.42, 95% CI 0.28–0.61), and providing fewer patients with family planning services. Among office-based physicians, factors associated with lower odds of frequent provision included specializing in obstetrics/gynecology (aOR 0.50, 95% CI 0.27–0.91) and family medicine (aOR 0.21, 95% CI 0.09–0.47) versus adolescent medicine, completing training ≥15 versus <5 years ago (aOR 0.27, 95% CI 0.09–0.83), and reporting that 0–24% of patients pay with Medicaid or other government healthcare assistance versus ≥50% (aOR 0.23, 95% CI 0.09–0.61). The reason most commonly reported by providers for infrequent DMPA provision was patient preference for another method.ConclusionsWhile most providers reported frequently providing DMPA to adolescents, training on evidence-based recommendations for contraception, focused on subgroups of providers with lower odds of frequent DMPA provision, may increase adolescents' access to contraception.ImplicationsAlthough >95% of providers considered depot medroxyprogesterone (DMPA) a safe contraceptive for adolescents, only 89% of public-sector providers and 64% of office-based physicians reported frequently providing DMPA to adolescents. Provider training on evidence-based recommendations for contraception counseling and provision may increase adolescents' access to DMPA and all methods of contraception.     

Improving Prenatal Diagnosis of Coarctation of the Aorta

Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

Rabies virus glycoprotein serology ELISA for measurement of neutralizing antibodies in sera of vaccinated human subjects

BackgroundVaccination provides protection against infection by inducing VNAs mainly against RABV surface GP. The measurement of VNAs to RABV is commonly used to assess the level of immunity in humans and animals after vaccination. A VNA titer of ≥ 0.5 IU/mL of sera indicates adequate response to vaccination. Here, we report the development and validation of a RABV GP serology ELISA kit for semi-quantitative measurement of VNA titers in sera of vaccinated human subjects.MethodsUsing a recombinant RABV GP expressed in mammalian cells as the capture antigen, the ELISA method was established using HuMAb NM57 reference initially and HRIG reference subsequently. The limit of detection (LOD), linear range, reproducibility, and precision of the method were examined. Specificity and sensitivity were established to assess the diagnostic accuracy.ResultsRABV GP for ELISA plate coating and optimal dilution of human serum sample was 1 µg/mL and 1:20, respectively. Multiple assays were carried out by different technicians at different laboratories for assay standardization. Using the HRIG reference, the LOD was found to be 0.02–0.06 IU/mL and the linear range was 0.2–10.0 IU/ mL. The inter-assay CVs were in the range of 6.60–10.79%, indicating the reproducibility. None of the 12 known negative human sera, tested positive by ELISA, highlighting the specificity. A total of 415 unknown positive human sera were double-blind tested by the RFFIT and ELISA. The VNA titer cut-off value of ELISA was set at 1.5 IU/mL to ensure no false-positive. The diagnostic specificity and sensitivity were 100% and 91.1%, respectively.ConclusionsThe validation data characterize this ELISA as a suitable method for semi-quantitative measurement of VNA titers in human serum samples to assess vaccination status. The ELISA kit can offer simplicity, speed, low cost and high throughput, making it a practical tool for monitoring the immune response following vaccination.     

平顶山市8岁学龄儿童患龋状况及影响因素分析

目的 了解平顶山市8岁学龄儿童龋病流行状况,探讨影响龋病发生发展的危险因素。 方法 参考“第三次全国口腔健康调查”的标准,采用分层整群抽样的方法,对1 762名适龄儿童进行口腔检查和问卷调查。 结果 平顶山市8岁学龄儿童患龋率84.68%,龋均4.79,城乡结合区域及农村儿童患龋率和龋均明显高于城市,差异有统计学意义(P＜0.05);乳、恒牙患龋率分别为83.65%、25.77%;城乡类型(OR=22.42)、家庭收入(OR=10.21)、睡前是否有吃零食习惯(OR=8.01)、吃完零食是否刷牙(OR=6.00)、进食甜食频率(OR=8.28)、刷牙方法(OR=8.88)、家长是否检查刷牙效果(OR=9.15)是影响患龋率的因素。 结论 平顶山市农村及城乡结合区域儿童患龋率较高,应加强口腔健康教育和龋病预防控制工作。     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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