Tag: pubmed

J Obstet Gynaecol. 2022 Nov 4:1-4. doi: 10.1080/01443615.2022.2141618. Online ahead of print.

ABSTRACT

This study aims to clarify the effect of postmenopausal bilateral oophorectomy on plasma steroid hormone levels. Women who were submitted in the postmenopausal period to hysterectomy for uterine benign conditions were divided into two groups: 18 women had isolated hysterectomy and 11 had hysterectomy with bilateral salpingo-oophorectomy. In both groups serum hormone levels were quantified by solid phase extraction and gas chromatography and tandem mass spectrometry. Differences in dehydroepiandrosterone (DHEA), testosterone, androstenedione and oestradiol were determined in both groups. The analysis revealed lower steroid levels in the bilateral salpingo-oophorectomy group when compared to the isolated hysterectomy group with statistically significant differences found for DHEA (5.8 ± 3.2 vs. 9.4 ± 4.4 ng/mL; p = 0.019) and oestradiol (0.69 ± 0.4 vs. 1.48 ± 4.3 ng/mL; p = 0.007). The results are consistent with a significant endocrine activity of the postmenopausal ovary. The clinical consequences of these findings need to be clarified and postmenopausal prophylactic bilateral salpingo-oophorectomy re-evaluated.IMPACT STATEMENTWhat is already known on this subject? Although it is consensual that premenopausal prophylactic bilateral oophorectomy should not be performed because it has harmful effects on women’s health, the evidence regarding the effects of postmenopausal prophylactic bilateral oophorectomy is scarce and this procedure continues to be a regular practice. Few studies have demonstrated that postmenopausal ovaries still have endocrine activity that may impact older women’s health.What do the results of this study add? This is the first study to compare hormone levels of postmenopausal women based on their hysterectomy and oophorectomy status using GC-MS/MS, a highly sensitive bioanalytical assay for the measurement of steroid hormones. Previous studies relied on immunoassays and did not compare DHEA levels, which according to the intracrinology theory is a precursor for androgens and oestrogens. In this study, statistically significant lower levels of DHEA and oestradiol were found after postmenopausal bilateral salpingo-oophorectomy.What are the implications of these findings for clinical practice and/or further research? This is a pilot study that may lead to further investigation in this area to clarify the impact of the prophylactic removal of postmenopausal ovaries on older women’s health and lead to changes in surgical procedures.

PMID:36331514 | DOI:10.1080/01443615.2022.2141618

JAMA Netw Open. 2022 Nov 1;5(11):e2240383. doi: 10.1001/jamanetworkopen.2022.40383.

ABSTRACT

IMPORTANCE: There is no consensus on interventions to slow the progress of hip displacement in patients with cerebral palsy.

OBJECTIVE: To investigate the efficacy of a novel hip brace in preventing progressive hip displacement in patients with cerebral palsy.

DESIGN, SETTING, AND PARTICIPANTS: This 2-group randomized clinical trial was conducted at 4 tertiary hospitals in South Korea from July 2019 to November 2021. Participants included children aged 1 to 10 years with nonambulatory cerebral palsy (Gross Motor Function Classification System level IV or V). Block randomization was used to assign an equal number of patients to the study and control groups via computerized random allocation sequences. Data were analyzed from November to December 2021.

INTERVENTIONS: The intervention group wore the hip brace for at least 12 hours a day for the study duration (ie, 12 months). Follow-up evaluations were performed after 6 and 12 months of wearing the brace. Both groups proceeded with conventional rehabilitation therapy during the trial.

MAIN OUTCOMES AND MEASURES: The primary outcome was the Reimers migration index (MI) on radiography, as assessed by 3 blinded investigators. Primary outcome variables were analyzed using linear mixed models. Secondary outcomes include change in the Caregiver Priorities & Child Health Index of Life with Disabilities, on which lower scores indicate better quality of life.

RESULTS: A total of 66 patients were included, with 33 patients (mean [SD] age, 68.7 [31.6] months; 25 [75.8%] boys) randomized to the intervention group and 33 patients (mean [SD] age, 60.7 [24.9] months; 20 [60.6%] boys) randomized to the control group. The baseline mean (SD) MI was 37.4% (19.3%) in the intervention group and 30.6% (16.3%) in the control group. The mean difference of the MI between the intervention group and control group was -8.7 (95% CI, -10.2 to -7.1) percentage points at 6 months and -12.7 (95% CI, -14.7 to -10.7) percentage points at 12 months. The changes in the Caregiver Priorities & Child Health Index of Life with Disabilities were favorable in the study group and reached statistical significance at the 6-month follow-up compared with the control group (difference, -14.2; 95% CI, -25.2 to -3.3).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the novel hip brace was significantly effective in preventing the progression of hip displacement, compared with the control group. It effectively improved quality of life in patients with nonambulatory cerebral palsy. Therefore, hip brace use could be a promising treatment method to delay hip surgery and improve the quality of life of patients with nonambulatory cerebral palsy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04033289.

PMID:36331502 | DOI:10.1001/jamanetworkopen.2022.40383

Hum Reprod. 2022 Nov 4:deac234. doi: 10.1093/humrep/deac234. Online ahead of print.

ABSTRACT

STUDY QUESTION: Are maternal urinary isoflavone (ISO) concentrations during pregnancy associated with anogenital distance (AGD) in infants at birth, and at 6 and 12 months of age?

SUMMARY ANSWER: Higher maternal urinary ISO concentrations during pregnancy were associated with longer AGD in infants of both sexes, and equol (EQU) and daidzein (DAD) were identified as the important ISO mixture components in the observed associations.

WHAT IS KNOWN ALREADY: Evidence of the association of prenatal exposure to ISO with offspring’s AGD is mainly derived from animal studies, which used different study designs and had inconsistent results. Only one human study has been reported and it found null associations between maternal ISO exposure during pregnancy and AGD among boys at birth, with a small sample size and a wide range of exposure windows. No human study on girls was found.

STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Shanghai-Minhang Birth Cohort Study), with pregnant women recruited at 12-16 weeks of gestation in Shanghai, China between April and December 2012. One thousand two hundred and twenty-five live singletons were left in the cohort at delivery of which 480 mother-infant pairs had data on both maternal urinary ISO concentrations and at least one AGD measurement and were included in the present study. Anopenile distance (AGDAP) and anoscrotal distance (AGDAS) of boys and anoclitoral distance (AGDAC) and anofourchette distance (AGDAF) of girls were measured at birth and at 6 and 12 months of age.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Multiple linear regression models were used to examine the associations between maternal ISO concentrations and AGD. Bayesian kernel machine regression (BKMR) was implemented to examine both the overall effects of ISO mixture and the single effect of each ISO and identify important components of ISO mixture.

MAIN RESULTS AND THE ROLE OF CHANCE: A general profile of higher concentrations of maternal ISO associated with longer AGD in infants of both sexes was observed, when maternal education, parity, BMI before pregnancy (BMI, categorical variable), passive smoking during early pregnancy, age at delivery, gestational weeks and infant body size were adjusted for. Among boys, EQU was associated with increased AGDAS at birth and at 6 and 12 months, and DAD was associated with increased AGDAP at birth. Among girls, the associations of EQU and DAD with increased AGDAC and AGDAF at birth were found. When gestational weight gain and feeding patterns of infants in the first 6 months were additionally adjusted for, and maternal BMI was adjusted for as a continuous variable, more pronounced associations were observed, especially for associations of genistein (GEN), DAD and glycitein (GLY) with increased AGDAP and AGDAS at 6 months in boys. However, these associations were not always observed in the highest tertile group, and no consistent dose-response relationships were found. Similar results were observed in BKMR models, showing positive correlations of concentration of ISO mixture with increased AGDAS at both 6 and 12 months among boys, and increased AGDAC and AGDAF at birth among girls. Statistically significant increments of 4.96 mm (95% credible interval (CrI): 1.40, 8.52) and 1.07 mm (95% CrI: 0.02, 2.13) in AGDAS at 6 months among boys and AGDAC at birth among girls, respectively, were observed at the 75th percentile of ISO mixture, compared with 25th percentile. EQU and DAD were identified as the important components among ISO-AGD associations.

LIMITATIONS, REASONS FOR CAUTION: First, due to the short half-lives of ISO, the accuracy of a single spot urine sample reflecting ISO exposure during pregnancy may be limited, and thus may cause non-differential misclassification. Second, despite the adjustments for several important covariates in the study, unmeasured and residual confounding factors may remain a concern. Third, false discovery due to multiple testing may remain. Finally, the reduced sample sizes attributed to the loss of follow-up and missing data of confounders may limit our ability to detect an association, if any existed.

WIDER IMPLICATIONS OF THE FINDINGS: Prenatal ISO exposure may affect the reproductive development of offspring. As ISO can be widely detected in pregnant women, especially in Eastern countries, more studies are warranted to provide evidence of the effects of prenatal ISO exposure on long-term reproductive outcomes.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Key Research and Development Program of China (2021YFC2701003), the National Natural Science Foundation of China (22076123), the Science and Technology Commission of Shanghai Municipality (21ZR1454700 and 20ZR1448000), the Shanghai Municipal Health Commission (20194Y0160) and Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation (CX2022-04). The authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:36331496 | DOI:10.1093/humrep/deac234

Rheumatology (Oxford). 2022 Nov 4:keac626. doi: 10.1093/rheumatology/keac626. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the present study was to detect preclinical changes in SLE patients in retinal microvascularization or retinal and optical nerve structure by optical coherence tomography.

METHODS: This cross-sectional, single-center study aimed to describe structural changes (macular and retinal nerve fiber layer [RNFL] thickness) by structural spectral-domain optical coherence tomography (SD-OCT) and perifoveal vascular (vascular density [VD] and perfusion [VP] and foveal avascular zone [FAZ] structural parameters) findings by OCT-angiography (OCTA) in 78 SLE patients and 80 healthy volunteers. In addition, we analyzed their association with clinical and laboratory parameters, medications received, disease duration and SLE activity and damage.

RESULTS: Structural parameters by SD-OCT and perifoveal vascular parameters by OCTA were decreased in SLE patients compared with controls. OCTA parameters (VD, VP and FAZ circularity) and macular thickness were also decreased in patients with longer disease duration (>10 years). The presence of antiphospholipid antibodies was associated with a decreased RNFL thickness, mainly in the inferior quadrants. Patients developing antiphospholipid syndrome also showed decreased RNFL thickness and OCTA flow changes. SD-OCT and OCTA results were not associated with disease activity. Foveal structural parameters were lower in patients with higher damage score.

CONCLUSION: SD-OCT and OCTA can detect preclinical structural and microcirculatory changes in SLE patients. Structural and perifoveal vascular macular changes in SLE patients are related with disease duration. Macular structural parameters were impaired in patients with higher disease damage. Antiphospholipid syndrome seems to be associated with preclinical damage of the optic nerve and impairment of the perifoveal microvasculature.

PMID:36331348 | DOI:10.1093/rheumatology/keac626

Cancer Commun (Lond). 2022 Nov 4. doi: 10.1002/cac2.12383. Online ahead of print.

ABSTRACT

BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.

METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.

RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group.

CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

PMID:36331328 | DOI:10.1002/cac2.12383

Eur Heart J. 2022 Nov 4:ehac594. doi: 10.1093/eurheartj/ehac594. Online ahead of print.

ABSTRACT

BACKGROUND: Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established.

METHODS AND RESULTS: Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41-1.81)].

CONCLUSION: This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.

PMID:36331326 | DOI:10.1093/eurheartj/ehac594

Eur Heart J. 2022 Nov 4:ehac615. doi: 10.1093/eurheartj/ehac615. Online ahead of print.

ABSTRACT

AIMS: Patients often require combination therapies to achieve LDL cholesterol (LDL-C) targets for the primary prevention of atherosclerotic cardiovascular disease. This study investigates the effect of inclisiran, a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 production, in primary prevention patients with elevated LDL-C despite statins.

METHODS AND RESULTS: This pre-specified analysis of the placebo-controlled, randomized ORION-11 trial included 203 individuals at risk of, but without prior, cardiovascular events and LDL-C ≥2.6 mmol/L, despite maximally tolerated statins. Inclisiran 284 mg or placebo was administered on Days 1, 90, and thereafter every 6 months up to 540 days. Co-primary endpoints were percentage LDL-C change from baseline to Day 510 and time-adjusted change from baseline after Day 90 and up to Day 540. Key secondary endpoints included percentage and absolute changes in atherogenic lipoproteins. Safety was assessed over 540 days. The mean baseline (SD) LDL-C was 3.6 (1.5) mmol/L. At Day 510, the placebo-corrected LDL-C change with inclisiran was -43.7% [95% confidence interval (CI): -52.8 to -34.6] with a corresponding time-adjusted change of -41.0% (95% CI: -47.8 to -34.2); (P < 0.0001). The placebo-corrected absolute change in LDL-C at Day 510 with inclisiran was -1.5 mmol/L (95% CI: -1.8 to -1.2), with a respective time-adjusted change of -1.3 mmol/L (95% CI: -1.6 to -1.1). Inclisiran significantly lowered non-HDL cholesterol and apolipoprotein B (apoB) at Day 510 vs. placebo (P < 0.0001 for both), with a greater likelihood of attaining lipoprotein and apoB goals, and was well-tolerated except for mainly mild, treatment-emergent adverse events at the injection site.

CONCLUSION: Inclisiran was generally well-tolerated in primary prevention patients with elevated LDL-C, who derived significant reductions in atherogenic lipoprotein levels with twice-yearly maintenance dosing.

PMID:36331315 | DOI:10.1093/eurheartj/ehac615

Dentomaxillofac Radiol. 2022 Nov 4:20220223. doi: 10.1259/dmfr.20220223. Online ahead of print.

ABSTRACT

OBJECTIVE: To establish prevalence and severity of external cervical resorption (ECR) in posterior teeth observed in bitewing (BW) radiographs in an epidemiological study of a 17-year-old patient population from community dentistry. Furthermore, to assess potential predisposing factors for ECR.

METHODS: Posterior BWs from 5,596 patients (2,717 females, 2,879 males; mean age 17.8 years) were assessed by three observers in order to detect ECR (using Heithersay’s classification system, severity classes 1-4). When ECR was suspected, cone beam CT (CBCT) was offered to verify diagnosis. Prevalence was estimated based on ECR suspected in BWs and finally in CBCT. Possible predisposing factors (orthodontic treatment, trauma, and periodontal disease) were recorded and assessed for association with ECR.

RESULTS: In 41 patients, ECR was suspected in BWs (suspected prevalence 0.73%). Thirty-two patients accepted CBCT examination, of which eight were verified to have ECR (final prevalence 0.18%). In 24 patients, other disease entities and abnormal tooth morphology, that had mimicked ECR in BWs, excluded ECR in CBCT. ECR severity ranged from class 1-3 in BW and 2-4 in CBCT. All but one case had not been diagnosed by the patient’s community dentist. No statistically significant association between predisposing factors and ECR was identified.

CONCLUSIONS: ECR had low prevalence in this adolescent population, as observed in both BWs and CBCT. Still, early detection of ECR is important for treatment prognosis, and attention should be paid to this disease entity when assessing BWs obtained for other diagnostic purposes. CBCT may subsequently aid in verifying the disease.

PMID:36331310 | DOI:10.1259/dmfr.20220223

Ann Med. 2022 Dec;54(1):3146-3156. doi: 10.1080/07853890.2022.2139410.

ABSTRACT

BACKGROUND: Role models are essential in medical education, yet empirical research is relatively insufficient on the influence of prosocial modelling on medical students’ career commitment. The prosocial behaviour of medical staff involved in the fight against the novel coronavirus disease 2019 (COVID-19) at the beginning of 2020 presents an opportunity to fill the research gap. We explored and compared the different associations of the two most important role models for medical students – parents and faculty- with medical students’ career commitment.

METHODS: The cross-sectional study was conducted with 99,559 undergraduate students majoring in clinical medicine in mainland China. Questions were asked to collect information about participants in the battle against COVID-19, medical students’ determination to practice medicine after graduation, as well as students’ socio-demographic characteristics. Chi-square tests and hierarchical regressions were performed to examine the associations between parent and faculty involvement and students’ career commitment.

RESULTS: The results showed statistically significant associations between prosocial modelling during the COVID-19 pandemic in China and students’ intention to pursue medical careers. The association of faculty involvement (OR = 1.165, p < .001) with students’ career commitment was greater than that of parents (OR = 0.970, p > .05). For faculty involvement, the association was stronger among male students (OR = 1.323, p < .001) and students who were already determined to be doctors (OR = 1.219, p < .001) before the pandemic.

CONCLUSIONS: Our study provides new evidence on the potential roles of parents and faculty in shaping medical students’ career commitment. Encouraging faculty to act as positive role models could help medical students increase their intention to become doctors.KEY MESSAGESProsocial modelling could enhance students’ intention to pursue medical careers.The association of prosocial behaviour of faculty is larger than that of parents on medical students.Those who have prior medical career commitment are much more likely to persist in the medical profession, and prosocial modelling of faculty is positively associated with their medical career commitment.

PMID:36331292 | DOI:10.1080/07853890.2022.2139410

Transl Vis Sci Technol. 2022 Nov 1;11(11):3. doi: 10.1167/tvst.11.11.3.

ABSTRACT

PURPOSE: The purpose of the study was to determine if aqueous glucose levels rise in a comparable time frame to interstitial fluid and could therefore be suitable for a continuous glucose monitoring (CGM) site.

METHODS: An intravenous glucose tolerance test was performed on five New Zealand white rabbits. Aqueous humor from the posterior and anterior chamber of the eye and venous blood were sampled for glucose concentration measurement. Glucose concentrations in the interstitial fluids were monitored using a CGM system. A compartment model was created to map the glucose response curves in each compartment. The delay in rising glucose concentrations between blood and interstitial fluid and aqueous humor in the posterior chamber and anterior chamber of the eye were analyzed.

RESULTS: The results showed a statistically similar time lag and rate of change in glucose concentrations between blood and interstitial fluids or aqueous humor in either the posterior or anterior chamber.

CONCLUSIONS: The results of this study add further support to the aqueous humor being used as an alternative CGM site.

TRANSLATIONAL RELEVANCE: The study provides the basis for developing an intraocular continuous glucose sensor that can overcome limitations of current CGM systems.

PMID:36331274 | DOI:10.1167/tvst.11.11.3