Clinical Features and Therapeutic Outcomes in Men with Advanced Prostate Cancer and DNA Mismatch Repair Gene Mutations

Mismatch repair (MMR) gene mutations are rare in prostate cancer, and their histological and clinical characteristics are largely unknown. We conducted a retrospective study to explore disease characteristics and treatment outcomes of men with metastatic prostate cancer harboring germline and/or somatic MMR mutations detected using clinical-grade genomic assays. Thirteen patients with a deleterious MMR gene mutation were identified. Median age was 64 yr, 75% had grade group 5 (Gleason sum 9 or 10), 23% had intraductal histology, 46% had metastatic disease at initial diagnosis, and 31% had visceral metastases. Most patients (46%) had MSH6 mutations, 73% demonstrated microsatellite instability, and median tumor mutational load was 18/Mb (range, 3–165 mutations/Mb). Surprisingly, responses to standard hormonal therapies were very durable (median progression-free survival [PFS] of 67 mo to initial androgen deprivation and median PFS of 26 mo to abiraterone/enzalutamide). Two of four men receiving PD-1 inhibitors achieved a ≥50% prostate-specific antigen response at 12 wk, with a median PFS duration in these four men of 9 mo. Despite aggressive clinical and pathological features, patients with MMR-mutated advanced prostate cancer appear to have particular sensitivity to hormonal therapies, as well as anecdotal responses to PD-1 inhibitors. Certain histological features (grade group 5, intraductal carcinoma) should prompt evaluation for MMR deficiency. These data are only hypothesis generating.

Rates of reoperation and nonoperative intervention within 30 days of bariatric surgery

BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ² for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG.     

Defining the relative contribution of health care environmental components to patient outcomes in the model of 30-day readmission after coronary artery bypass graft (CABG)

BackgroundPatient outcomes following health care interventions may be dependent on a variety of factors: patient, surgeon, hospital, information technology, and temporal, cultural, and socioeconomic factors, among others. In this study, we characterize the relative contribution of each of these factors using a model of 30-day readmission following coronary artery bypass graft.MethodsThe Healthcare Cost and Utilization Project, the American Hospital Association Annual Health Survey Databases, the Healthcare Information and Management Systems Society, and the Distressed Communities Index from 2010 to 2013 were linked for Florida, Iowa, Massachusetts, Maryland, New York, and Washington. Logistic regression, random forest, decision tree, gradient boosting, k-nearest-neighbors classification, and XGBoost tree models were implemented. Modeling results were compared on the basis of predictive accuracy, sensitivity, specificity, and area under the curve. Decision tree performed best and was selected for further analysis. A gradient-boosted model was used to quantify factor contribution.ResultsThe model had 45,352 patients, 54,096 admissions, and a 16.2% 30-day readmission rate after coronary artery bypass graft. The top 10 predictors were disposition at discharge, number of chronic conditions, total procedures, median household income, adults without high school diplomas, primary payer method, Agency for Healthcare Research and Quality comorbidity: renal failure, patient location (urban-rural), admission type, and age categories. The top 3 socioeconomic predictors were estimated state median household income, adults without high school diplomas, and patient location (urban versus rural designation). The relative contribution of patient/temporal, socioeconomic, hospital information technology, and hospital factors to readmission is 83.45%, 5.71%, 6.34%, and 4.31%, respectively.ConclusionIn this model, the contribution of socioeconomic factors is substantive but lags significantly behind patient/temporal factors. With ever increasing availability of data, identification of contributors to patient outcomes within the overall health care macroenvironment will allow prioritization of interventions.     

The perineal midsagittal view in male fetuses — pivotal for assessing genitourinary disorders

A wide range of genitourinary pathologies can be diagnosed in utero, from a simple vesicoureteral reflux to a more complex disorder of sexual differentiation. The prognosis and neonatal management of these conditions differ significantly. Evaluation of the fetal perineal anatomy is paramount to making the right diagnosis. The aim of this pictorial essay is to show sonographers how to acquire a perineal midsagittal view in a male fetus, and to demonstrate how this specific view allows assessment of the urethra and penis, to differentiate various genitourinary pathologies.

     

Anticipated and unanticipated complications of severe dengue in a primigravida

As the incidence of dengue is rising among adults more cases of dengue fever are being reported during pregnancy. Physiological changes of pregnancy mask the pathognomonic features of severe dengue such as increased hematocrit, thrombocytopenia, and leukopenia and a high index of suspicion are required in endemic areas. Massive hemorrhage may complicate operative deliveries in unsuspected patients. World Health Organization recommends that all patients with severe dengue should be admitted to a hospital with access to intensive care facilities and blood transfusion. We present the successful management of hemorrhage and unanticipated complications of severe dengue in a young primigravida admitted to the Intensive Care Unit after an emergency cesarean section.