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Purpose Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. Methods 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18–24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. Results Denosumab significantly increased TBS values (from 1.270 to 1.323; P  < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P  = 0.021). During treatment with BPs, TBS did not significantly change ( P  = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs ( P  = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women ( P  = 0.003), without significant differences in changes of BMD at any skeletal site. Conclusions TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Background Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation. Methods One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles. Results The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans ( p  < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation ( p  < 0.001). Weight and BMI were inversely associated with testicular dose ( p  < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia. Conclusion Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility. Trial registration : retrospectively registered.

Background While low testosterone (T) was described as a predictor of unfavorable coronavirus-disease 19 (COVID-19) outcome in men, data concerning the role of T in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are scant and limited to small cohorts. This study investigated the relationship between serum T values and outcomes of COVID-19 in a large female hospitalized cohort. Methods One-hundred-sixty-eight adult women (median age 77, range 18–100 years; 154 in post-menopause) hospitalized for COVID-19 were assessed for PaO2/Fio2 ratio, serum T and inflammatory parameters. Results Median duration for hospital stay was 14.2 days (range 1–115) with overall mortality of 26% ( n  = 44). Subjects who died were significantly older ( p  < 0.001), had significantly more comorbidities ( p  = 0.015) and higher serum T ( p  = 0.040), white blood cells ( p  = 0.007), c-reactive protein (CRP; p  < 0.001), interleukin-6 (IL-6; p  < 0.001), procalcitonin (PCT; p  < 0.001), lactate dehydrogenase (LDH; p  = 0.001), D-dimer ( p  = 0.035), fibrinogen ( p  = 0.038) and lower serum free-triiodothyronine (FT3; p  < 0.001) and luteinizing hormone (LH; p  = 0.024) values. In post-menopausal women, significant associations were observed between T levels and serum CRP (rho: 0.23; p  = 0.002), IL-6 (rho: 0.41; p  < 0.001), LDH (rho: 0.34; p  < 0.001), D-Dimer (rho: 0.21; p  = 0.008), PCT (rho: 0.26; p  = 0.001) and HDL cholesterol (rho:  – 0,22, p  = 0.008). In multivariate regression analyses, serum T maintained the significant association with mortality after correction for age, coexistent comorbidities and serum LH and FT3, whereas it was lost after correction for inflammatory parameters. Conclusion In females, high serum T levels might be a mirror of inflammatory phenotype and worse COVID-19 course.

In a multicenter, double-blind, placebo-controlled, randomized study, subjects with type 2 diabetes mellitus and hypertension but normal urinary albumin levels were treated with an angiotensin-converting–enzyme (ACE) inhibitor (trandolapril) and a non-dihydropyridine calcium-channel blocker (verapamil) alone or in combination to investigate whether treatment could forestall the development of microalbuminuria, which heralds diabetic nephropathy. The use of trandolapril alone or with verapamil appeared to be effective, whereas verapamil alone was no better than placebo. ACE inhibition may prevent or retard the development of microalbuminuria in patients with type 2 diabetes mellitus. Type 2 diabetes mellitus is a public health concern, and projections of its future effect are alarming. According to the World Health Organization, diabetes affects more than 170 million people worldwide, and this number will rise to 370 million by 2030. 1 About one third of those affected will eventually have progressive deterioration of renal function. 2 The first clinical sign of renal dysfunction in patients with diabetes is generally microalbuminuria (a sign of endothelial dysfunction that is not necessarily confined to the kidney), 4 which develops in 2 to 5 percent of patients per year. 5 , 6 In type 2 diabetes, unlike type . . .

AimsThere is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment.MethodsData were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint.ResultsData from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90–4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as − 2.2% (24 mol/mol) in the former versus − 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups.ConclusionsGlycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.

Purpose To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). Methods A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. Results Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. Conclusion Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

The annual incidence of listeriosis in Italy is lower (0·19–0·27 per 100 000 inhabitants per year) than in Europe (0·34–0·52 per 100 000 inhabitants per year). Since the observed incidence of listeriosis may be biased downward for underdiagnosis or under-reporting, this work aims to estimate the real incidence of listeriosis during a 9-year period in the Lombardy region, Italy. Data on listeriosis cases were collected from national mandatory notification system (MAINF) and Laboratory-based Surveillance System (LabSS). The two sources were cross-matched and capture–recapture method was applied to estimate the number of undetected cases and the real incidence of invasive listeriosis. Five hundred and eighty invasive listeriosis cases were detected by the two sources between 2006 and 2014: 50·2% were identified only via MAINF, 16·7% were recorded only via LabSS, overlaps occurred in 192 cases (33·1%). The mean annual incidence detected only by MAINF was 0·56 per 100 000 inhabitants, which rose to 0·67 per 100 000 considering also the cases detected by LabSS. The capture–recapture method allowed to estimate an incidence of 0·84 per 100 000. The high incidence of listeriosis may be due to improved sensitivity of the surveillance system, but also reflect a real increase, associated with an increased population at risk.

Background: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. Methods: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3–4, PSA >20 ng ml −1 or biopsy Gleason score 8–10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. Results: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29–88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32–0.80; P =0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21–0.43; P <0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. Conclusions: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0–1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8–4·6) for radiographic progression-free survival and 4·4 years (3·5–5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41–0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69–0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34–0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59–0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. Janssen-Cilag, Ipsen, Sanofi, and the French Government.