Metastasis-directed Therapy (SBRT) Guided by PET-CT 18F-CHOLINE Versus PET-CT 68Ga-PSMA in Castration-sensitive Oligorecurrent Prostate Cancer: A Comparative Analysis of Effectiveness

BackgroundThe present analysis aims to compare the impact of 18F-fluorocholine (¹⁸F-choline) and gallium-68 prostate-specific membrane antigen (⁶⁸Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)–guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC).Materials and MethodsInclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by ¹⁸F-choline or ⁶⁸Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered.ResultsA total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent ⁶⁸Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the ⁶⁸Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET–guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with ⁶⁸Ga-PSMA-based SBRT.ConclusionIn the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the ¹⁸F-choline-PET cohort. Randomized trials are advocated.     

Alcance de la implementación en Cataluña de las estrategias de salud reproductiva (2008-2017)

ObjectiveWe analyse how reproductive health strategies have been incorporated into the everyday activities of the services and the resulting transformation of professional and user practices.MethodCartographic research taking a multi-sited ethnographic approach that seeks to reveal the processes of transformation. Data generation techniques featuring participant observation and situated interviews. Discourse analysis of the text corpus using three analytical axes based on three main lines of action promoted by the strategies.ResultsWe identified transformations in: 1) demedicalisation: an increase in midwives’ know-how and autonomy, changes in episiotomy practice and the facilitation of bonding practices; 2) warmth of care: incorporation of women's needs and expectations and improvements in the comfortableness of birth settings, especially in assistance at physiological birth; and 3) participation: actions that foster shared decision-making and the involvement of the persons accompanying women in labour.ConclusionsAbove all, transformation is visible in the incorporation of new attitudes, sensibilities and practices that have developed around the old structures, especially during physiological childbirth. The more technological areas have been less permeable to change. Risk management in decision-making and addressing diversity are identified as areas where transformation is less evident.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Psychometric properties of the Persian version of the Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC) in unsuccessful sexual situations

The aim of this study was to translate and adapt to Persian, and to assess psychometric properties of the Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC). A total of 265 Iranian participants (121 women and 144 men) were recruited for this study. A principal component analysis (PCA) with varimax rotation and subsequent confirmatory factor analysis revealed a best fitting five-factor structure similar to the original QCSASC: Incompetence, Undesirability, Abandon/Rejection, Powerless/Helpless, and Difference. However, in the Iranian sample, the original Self-Depreciation dimension was included in the Incompetence and Undesirability factors. An Abandon/Rejection dimension was also evident, and may be explained by cultural, social, and religious factors in the Iranian culture. Additionally, reliability analysis has supported the internal consistency (adequate Cronbach's alpha values) and temporal stability (test–retest reliability) of the QCSASC in an Iranian sample. The findings suggest the adequacy of the Persian version of the QCSASC to assess cognitive schemas in sexual context among Iranian men and women.     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.