No abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8þ) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3 0 region of BRCA2 (c.7914þ) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR ¼ 1.78; 95% confidence interval (CI), 1.25-2.52; P ¼ 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR ¼ 3.11; 95% CI, 1.63-5.95; P ¼ 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR ¼ 2.83; 95% CI, 1.71-4.68; P ¼ 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR ¼ 4.95; 95% CI, 2.12-11.54; P ¼ 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer.Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

In this large consecutive cohort study of LSG, proximal staple line reinforcement (buttress material or suture) reduced the risk of a leak. The risk of a proximal leak was much higher in the surgeons first 100 cases, which has implications for training and supervision during this "learning curve" period.

Introduction On February 20, 2020, a severe case of pneumonia due to SARS-CoV-2 was diagnosed in northern Italy (Lombardy). Some studies have identified obesity as a risk factor for severe disease in patients with COVID-19. The purpose of this study was to investigate the incidence of SARS-CoV-2 infection and its severity in patients who have undergone bariatric surgery. Material and Methods During the lockdown period (until May 2020), we contacted operated patients by phone and social networks (e.g., Facebook) to maintain constant contact with them; in addition, we gave the patients a dedicated phone number at which to call us for emergencies. We produced telemedicine and educational videos for obese and bariatric patients, and we submitted a questionnaire to patients who had undergone bariatric surgery in the past. Results A total of 2145 patients (313 male; 1832 female) replied to the questionnaire. Mean presurgical BMI: 44.5 ± 6.8 kg/m 2 . Mean age: 44.0 ± 10.0 year. Mean BMI after surgery: 29.3 ± 5.5 kg/m 2 ( p < 0.05). From February to May 2020, 8.4% of patients reported that they suffered from at least one symptom among those identified as related to SARS-CoV-2 infection. Thirteen patients (0.6%) tested positive for COVID-19. Six patients (0.3%) were admitted to the COVID Department, and 2 patients (0.1%) were admitted to the ICU. Conclusions Although the reported rates of symptoms and fever were high, only 0.6% of patients tested positive for COVID-19. Among more than 2000 patients who underwent bariatric surgery analyzed in this study, only 0.1% needed ICU admission. Supplementary Information The online version contains supplementary material available at 10.1007/s11695-020-05085-z.

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions (90%), encompassing multiple genes and including the retinoic acid-induced 1 gene (RAI1), or by pathogenic variants in RAI1 itself (10%). RAI1 is a dosage-sensitive gene expressed in many tissues and acting as transcriptional regulator. The majority of individuals exhibit a mild-to-moderate range of intellectual disability. The behavioral phenotype includes significant sleep disturbance, stereotypes, maladaptive and self-injurious behaviors. In this review, we summarize current clinical knowledge and therapeutic approaches. We further discuss the common biological background shared with other conditions commonly retained in differential diagnosis.

Early age at onset of breast cancer (eoBC) is suggestive of an increased genetic risk. Although genetic testing is offered to all eoBC-affected women, in isolated cases the detection rate of pathogenic variants is <10%. This study aimed at assessing the role of constitutive promoter methylation at BC-associated loci as an underlying predisposing event in women with eoBC and negative family history. Promoter methylation at 12 loci was assessed by the MassARRAY technology in blood from 154 BRCA1/2 negative patients with eoBC and negative family history, and 60 healthy controls. Hypermethylation was determined, within each promoter, by comparing the patient’s mean methylation value with thresholds based on one-sided 95% bootstrap confidence interval of the controls’ mean. Three patients had hypermethylated results, two at BRCA1 and one at RAD51C. Analyses on tumor tissue from the patient exceeding the highest threshold at BRCA1 revealed a mean methylation >60% and loss of heterozygosity at chromosome 17q. The patient hypermethylated at RAD51C showed low methylation in the tumor sample, ruling out a role for methylation-induced silencing in tumor development. In isolated eoBC patients, BRCA1 constitutive promoter methylation may be a predisposing event. Further studies are required to define the impact of methylation changes occurring at BC-predisposing genes and their role in tumorigenesis.

No abstract

No abstract