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In this study, the androgen-receptor inhibitor enzalutamide improved progression-free and overall survival in men with castration-resistant metastatic prostate cancer who had not received chemotherapy. Prostate cancer is the most commonly diagnosed cancer and the sixth leading cause of cancer-related death among men worldwide. 1 Strategies to block androgen-receptor signaling have formed the backbone of prostate-cancer therapy since the first description of the hormonal dependence of this cancer in 1941. 2 Advances in endocrine therapies have improved survival in men with high-risk locoregional prostate cancer. 3 , 4 However, new hormonal agents have been shown to extend survival in men with metastatic castration-resistant disease. 5 – 9 In most patients who are treated for advanced recurrent prostate cancer with androgen-deprivation therapy (comprising a luteinizing hormone–releasing hormone [LHRH] analogue or orchiectomy with . . .

Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. The study was registered on clinicaltrials.gov (NCT06110143).

The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. 67 men were enrolled into the study. 62 patients (92·5%, 95% CI 86·2–98·8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer. Astellas Pharma Inc, Medivation Inc.

Managing everyday life with type 2 diabetes can be challenging. In particular, men considered vulnerable are often portrayed as lacking self-management. This paper challenges this assumption by highlighting the unheeded knowledge and self-care practices these men develop, and by exploring how these are included in healthcare encounters at an outpatient clinic in Denmark. Data were collected through observations of clinical practice and subsequent interviews with 12 men who have type 2 diabetes. A thematic analysis was conducted to explore their daily experiences of managing chronic illness and their encounters with healthcare professionals. Men considered vulnerable manifest important knowledge and strategies in managing type 2 diabetes in their daily lives, often perceiving the illness as barely present. Their encounters with healthcare professionals, particularly females, often draw on repertoires from previous experiences with (often female) care professionals and seem to follow a certain script for (female) carers encountering disadvantaged (male) care recipients. These dynamics frequently overlook the men's lived experiences and self-management knowledge. Men considered vulnerable develop important coping strategies and knowledge for managing type 2 diabetes in their everyday lives. However, their encounters with health professionals often perpetuate gendered assumptions and exclusion of their everyday experiences and knowledge.

The risk of missing prostate cancer in the transrectal ultrasound-guided systematic biopsies of the prostate in men with suspected prostate cancer is a key problem in urological oncology. Repeat biopsy or MRI-guided biopsies have been suggested to increase sensitivity for diagnosis of prostate cancer, but the risk of disease-specific mortality in men who present with raised prostate-specific antigen (PSA) concentration and a benign initial biopsy result remains unknown. We investigated the risk of overall and prostate cancer-specific mortality in men with a benign initial biopsy set. Data were extracted from the Danish Prostate Cancer Registry—a population-based registry including all men undergoing histopathological assessment of prostate tissue. All men who were referred for transrectal ultrasound-guided biopsy for assessment of suspected prostate cancer between Jan 1, 1995, and Dec 31, 2011, in Denmark were eligible for inclusion. Follow-up data were obtained on April 28, 2015. The primary endpoint was the cumulative incidence of prostate cancer-specific mortality, analysed in a competing risk setting, with death from other causes as the competing event. Between Jan 1, 1995, and Dec 31, 2011, 64 430 men were referred for transrectal ultrasound-guided biopsy, of whom 63 454 were eligible for inclusion. Median follow-up was 5·9 years (IQR 3·8–8·5) and the total follow-up time, from the enrolment of the first patient on Jan 1, 1995, until the extraction of causes of death on April 28, 2015, was 20 years. 10 407 (30%) of 35 159 men with malignant initial biopsy sets died from prostate cancer, compared with 541 (2%) of 27 181 men with benign initial biopsy sets. Estimated overall 20-year mortality was 76·1% (95% CI 73·0–79·2). In all men referred for transrectal ultrasound-guided biopsy, the cumulative incidence of prostate cancer-specific mortality after 20 years was 25·6% (24·7–26·5) versus 50·5% (47·5–53·5) for mortality from other causes. In men with benign initial biopsy sets, the cumulative incidence of prostate cancer-specific mortality was 5·2% (3·9–6·5) versus 59·9% (55·2–64·6) for mortality from other causes. In men with PSA concentrations 10 μg/L or lower and benign initial biopsy sets (2779 men), the cumulative incidence of prostate cancer-specific mortality was 0·7% (0·2–1·3). Cumulative incidence of prostate cancer specific mortality in men with benign initial biopsy sets was 3·6% (95% CI 0·1–7·2) for men with a PSA higher than 10 ng/mL but 20 ng/mL or less (855 men) and 17·6% (12·7–22·4) and for men with a PSA higher than 20 ng/mL (454 men). The first systematic transrectal ultrasound-guided biopsy set holds important prognostic information. The 20-year risk of prostate cancer-specific mortality in men with benign initial results is low. Our findings question whether men with low PSA concentration and a benign initial biopsy set should undergo further diagnostic assessment in view of the high risk of mortality from other causes. Capital Region of Denmark's Fund for Health Research, Danish Cancer Society, Danish Association for Cancer Research, and Krista and Viggo Petersen's Foundation.

Cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO2 during normal aging are still controversial, as some authors find decreases of both CBF and CMRO2 but increased OEF, while others find no change, and yet other find divergent changes. In this reanalysis of previously published results from positron emission tomography of healthy volunteers, we determined CMRO2 and CBF in 66 healthy volunteers aged 21 to 81 years. The magnitudes of CMRO2 and CBF declined in large parts of the cerebral cortex, including association areas, but the primary motor and sensory areas were relatively spared. We found significant increases of OEF in frontal and parietal cortices, excluding primary motor and somatosensory regions, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions most affected by age are the areas that are most vulnerable to neurodegeneration.

BackgroundKidney dosimetry after peptide receptor radionuclide therapy using 177Lu-labelled somatostatin analogues is a procedure with multiple steps. We present the SPECT/CT-based implementation at Aarhus University Hospital and evaluate the uncertainty of the various steps in order to estimate the total uncertainty and to identify the major sources of uncertainty. Absorbed dose data from 115 treatment fractions are reported. ResultsThe total absorbed dose with uncertainty is presented for 59 treatments with [177Lu]Lu-DOTATOC and 56 treatments with [177Lu]Lu-DOTATATE. For [177Lu]Lu-DOTATOC the mean and median specific absorbed dose (dose per injected activity) is 0.37 Gy/GBq and 0.38 Gy/GBq, respectively, while for [177Lu]Lu-DOTATATE the median and mean are 0.47 Gy/GBq and 0.46 Gy/GBq, respectively. The uncertainty of the procedure is estimated to be about 13% for a single treatment fraction, where the absorbed dose calculation is based on three SPECT/CT scans 1, 4 and 7 days post-injection, while it increases to about 19% if only a single SPECT/CT scan is performed 1 day post-injection.ConclusionsThe specific absorbed dose values obtained with the described procedure are comparable to those from other treatment sites for both [177Lu]Lu-DOTATOC and [177Lu]Lu-DOTATATE, but towards the lower end of the range of reported values. The estimated uncertainty is also comparable to that from other reports and judged acceptable for clinical and research use, thus proving the kidney dosimetry procedure a useful tool. The greatest reduction in uncertainty can be obtained by improved activity determination, partial volume correction and additional SPECT/CT scans.

BackgroundBoth [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL). However, direct comparisons of the performance of the two tracers are only available in small series. We conducted a retrospective comparative analysis of FDOPA and DOTATOC to assess their sensitivity and accuracy in detecting PPGL when administered based on suspicion of PPGL. We consecutively included patients referred on suspicion of PPGL or PPGL recurrence who were scanned with both FDOPA and DOTATOC. Both scans were reviewed retrospectively by two experienced observers, who were blinded to the final diagnosis. The assessment was made both visually and quantitatively. The final diagnosis was primarily based on pathology.ResultsIn total, 113 patients were included (97 suspected of primary PPGL and 16 suspected of recurrence). Of the 97 patients, 51 had pheochromocytomas (PCC) (in total 55 lesions) and 6 had paragangliomas (PGL) (in total 7 lesions). FDOPA detected and correctly localized all 55 PCC, while DOTATOC only detected 25 (sensitivity 100% vs. 49%, p < 0.0001; specificity 95% vs. 98%, p = 1.00). The negative predictive value (100% vs. 63%, p < 0.001) and diagnostic accuracy (98% vs. 70%, p < 0.01) were higher for FDOPA compared to DOTATOC. FDOPA identified 6 of 6 patients with hormone producing PGL, of which one was negative on DOTATOC. Diagnostic performances of FDOPA and DOTATOC were similar in the 16 patients with previous PPGL suspected of recurrence.ConclusionsFDOPA is superior to DOTATOC for localization of PCC. In contrast to DOTATOC, FDOPA also identified all PGL but with a limited number of patient cases.

ObjectiveTo investigate the risk of prostate cancer-specific mortality (PCSM) following initial negative systematic transrectal ultrasound-guided (TRUS) prostate biopsies.DesignSystematic review.Data sourcesPubMed and Embase were searched using a string combination with keywords/Medical Subject Headings terms and free text in the search builder. Date of search was 13 April 2020.Study selectionStudies addressing PCSM following initial negative TRUS biopsies. Randomised controlled trials and population-based studies including men with initial negative TRUS biopsies reported in English from 1990 until present were included.Data extractionData extraction was done using a predefined form by two authors independently and compared with confirm data; risk of bias was assessed using the Newcastle–Ottawa Scale for cohort studies when applicable.ResultsFour eligible studies were identified. Outcomes were reported differently in the studies as both cumulative incidence and Kaplan-Meier estimates have been used. Regardless of the study differences, all studies reported low estimated incidence of PCSM of 1.8%–5.2% in men with negative TRUS biopsies during the following 10–20 years. Main limitation in all studies was limited follow-up.ConclusionOnly a few studies have investigated the risk of PCSM following initial negative biopsies and all studies included patients before the era of MRI of the prostate. However, the studies point to the fact that the risk of PCSM is low following initial negative TRUS biopsies, and that the level of prostate-specific antigen before biopsies holds prognostic information. This may be considered when advising patients about the need for further diagnostic evaluation.PROSPERO registration numberCRD42019134548.

BackgroundIn the case of extravasation of radioactive drugs used in peptide-receptor radionuclide therapy of neuroendocrine tumors, or in radionuclide therapy in general, rapid action is important to reduce or avoid complications. The literature on extravasation of drugs for radionuclide therapy is sparse. Based on the present case, we discuss handling and consequences of extravasation. Further, we demonstrate that dosimetry can aid in judging if the treatment of neuroendocrine tumors is satisfactory even after extravasation.Case presentationA case of extravasation of [177Lu]Lu-DOTATOC with a treatment strategy involving exercise and elevation of the affected arm and application of a compression bandage and heating is reported. Redistribution of the drug is verified and quantified by whole-body imaging and quantitative SPECT/CT and measurements of the dose rate at contact with the injection site. [177Lu]Lu-DOTATOC was redistributed to tumors and organs within 1 day. The patient did not report any discomfort during or after hospitalization, and no side effects related to extravasation were observed. Quantitative SPECT/CT scans at the subsequent treatment cycle of the same patient were analyzed for a comparison between the treatments. Dosimetry showed the treatments were similar with respect to the kidney and tumor absorbed doses. The radiation dose to the epidermal basal layer near the injection site was estimated and found to be consistent with the lack of side effects.ConclusionsThe treatment of extravasation was successful, and the redistribution of the drug can be easily verified through measurement of the dose rate at contact with the skin. From the results of dosimetry, it was assessed that no change of the treatment course was necessary to compensate for a possibly incomplete treatment as a result of the extravasation.