Oncologic outcomes among Black and White men with grade group 4 or 5 (Gleason score 8-10) prostate cancer treated primarily by radical prostatectomy.

BACKGROUND: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy. METHODS: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men. RESULTS: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis. CONCLUSIONS: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy.

Intermittent fasting for the prevention of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes are at the forefront of preventing the disease. This includes advice such as increasing physical activity and having a healthy balanced diet to reduce risk factors. Intermittent fasting (IF) is a popular dietary plan involving restricting caloric intake to certain days in the week such as alternate day fasting and periodic fasting, and restricting intake to a number of hours in a given day, otherwise known as time-restricted feeding. IF is being researched for its benefits and many randomised controlled trials have looked at its benefits in preventing CVD. OBJECTIVES: To determine the role of IF in preventing and reducing the risk of CVD in people with or without prior documented CVD. SEARCH METHODS: We conducted our search on 12 December 2019; we searched CENTRAL, MEDLINE and Embase. We also searched three trials registers and searched the reference lists of included papers. Systematic reviews were also viewed for additional studies. There was no language restriction applied. SELECTION CRITERIA: We included randomised controlled trials comparing IF to ad libitum feeding (eating at any time with no specific caloric restriction) or continuous energy restriction (CER). Participants had to be over the age of 18 and included those with and without cardiometabolic risk factors. Intermittent fasting was categorised into alternate-day fasting, modified alternate-day fasting, periodic fasting and time-restricted feeding. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies for inclusion and extraction. Primary outcomes included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure. Secondary outcomes include the absolute change in body weight, and glucose. Furthermore, side effects such as headaches and changes to the quality of life were also noted. For continuous data, pooled mean differences (MD) (with 95% confidence intervals (CIs)) were calculated. We contacted trial authors to obtain missing data. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: Our search yielded 39,165 records after the removal of duplicates. From this, 26 studies met our criteria, and 18 were included in the pooled analysis. The 18 studies included 1125 participants and observed outcomes ranging from four weeks to six months. No studies included data on all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure at any point during follow-up. Of quantitatively analysed data, seven studies compared IF with ab libitum feeding, eight studies compared IF with CER, and three studies compared IF with both ad libitum feeding and CER. Outcomes were reported at short term (≤ 3 months) and medium term (> 3 months to 12 months) follow-up. Body weight was reduced with IF compared to ad libitum feeding in the short term (MD -2.88 kg, 95% CI -3.96 to -1.80; 224 participants; 7 studies; low-certainty evidence). We are uncertain of the effect of IF when compared to CER in the short term (MD -0.88 kg, 95% CI -1.76 to 0.00; 719 participants; 10 studies; very low-certainty evidence) and there may be no effect in the medium term (MD -0.56 kg, 95% CI -1.68 to 0.56; 279 participants; 4 studies; low-certainty evidence). We are uncertain about the effect of IF on glucose when compared to ad libitum feeding in the short term (MD -0.03 mmol/L, 95% CI -0.26 to 0.19; 95 participants; 3 studies; very-low-certainty of evidence) and when compared to CER  in the short term: MD -0.02 mmol/L, 95% CI -0.16 to 0.12; 582 participants; 9 studies; very low-certainty; medium term: MD 0.01, 95% CI -0.10 to 0.11; 279 participants; 4 studies; low-certainty evidence). The changes in body weight and glucose were not deemed to be clinically significant. Four studies reported data on side effects, with some participants complaining of mild headaches. One study reported on the quality of life using the RAND SF-36 score. There was a modest increase in the physical component summary score. AUTHORS' CONCLUSIONS: Intermittent fasting was seen to be superior to ad libitum feeding in reducing weight. However, this was not clinically significant. There was no significant clinical difference between IF and CER in improving cardiometabolic risk factors to reduce the risk of CVD. Further research is needed to understand the safety and risk-benefit analysis of IF in specific patient groups (e.g. patients with diabetes or eating disorders) as well as the effect on longer-term outcomes such as all-cause mortality and myocardial infarction.

Does the clinical effectiveness of Mitraclip compare with surgical repair for mitral regurgitation?

BACKGROUND: Surgical repair of the mitral valve has long been the established therapy for degenerative mitral regurgitation (MR). Newer transcatheter methods over the last decade, such as the MitraClip, serve to restore mitral function with reduced procedural burden and enhanced recovery. This study aims to compare the shortterm and midterm outcomes of MitraClip insertion with surgical repair for MR. METHODS: A systematic review of the literature was conducted for studies comparing outcomes between surgical repair and MitraClip. The initial search returned 1850 titles, from which 12 studies satisfied the inclusion criteria (one randomized controlled trial and 11 retrospective studies). RESULTS: The final analysis comprised 4219 patients (MitraClip 1210; surgery 3009). Operative mortality was not different between the groups (odds ratio [OR] = 1.63, 95% confidence interval [CI]: [0.63-4.23]; p = .317). Length of hospital stay was significantly shorter in the MitraClip group (standardized mean difference [SMD] = 0.882, 95% CI: [0.77-0.99]; p < .001) with considerable heterogeneity (I2 > 90%; p < .001). The rate of reoperation on the mitral valve was lower in the surgical group (OR = 0.392; 95% CI: [0.188-0.817]; p = .012) as was the rate of MR recurrence grade moderate or above (OR = 0.29; 95% CI: [0.19-0.46]; p < .001) during midterm follow up. Long term survival (4-5 years) was also similar between both groups (hazard ratio = 0.70; 95% CI: [0.35-1.41]; p = .323). CONCLUSIONS: This study highlights the superior midterm durability of surgical valve repair for MR compared with the MitraClip.

Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery.

We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surgery can induce an oxidative stress response. However, the role of the humoral immune system in clearance of oxidized LDL following such an insult is unknown. Plasma samples were obtained from a prospective cohort of 131 patients undergoing major non-cardiac vascular surgery, with samples obtained preoperatively and at 24- and 72 h postoperatively. Enzyme-linked immunoassays were developed to assess MDA-LDL-related antibodies and complexes. Adverse events were myocardial infarction (primary outcome), and a composite of unstable angina, stroke and all-cause mortality (secondary outcome). MDA-LDL significantly increased at 24 h post-operatively (p < 0.0001). Conversely, levels of IgG and IgM anti-MDA-LDL, as well as IgG/IgM-MDA-LDL complexes and total IgG/IgM, were significantly lower at 24 h (each p < 0.0001). A smaller decrease in IgG anti-MDA-LDL related to combined clinical adverse events in a post hoc analysis, withstanding adjustment for age, sex, and total IgG (OR 0.13, 95% CI [0.03-0.5], p < 0.001; p value for trend <0.001). Major vascular surgery resulted in an increase in plasma MDA-LDL, in parallel with a decrease in antibody/complex levels, likely due to antibody binding and subsequent removal from the circulation. Our study provides novel insight into the role of the immune system during the oxidative stress of major surgery, and suggests a homeostatic clearance role for IgG antibodies, with greater reduction relating to downstream adverse events.

Exploring the learning curve, pathological outcomes and perioperative morbidity of laparoscopic partial nephrectomy performed for renal mass.

PURPOSE: We investigated the learning curve, pathological results and perioperative morbidity of laparoscopic partial nephrectomy (LPN). MATERIALS AND METHODS: The records of all LPN cases at our institution between January 1999 and March 2004 were reviewed. Of 223 cases 217 (97.3%) were performed for an enhancing renal mass. RESULTS: Mean tumor size was 2.6 cm (range 1 to 10) and 95.4% of patients had a normal contralateral kidney. Transient vascular control was performed in 75.1% of cases. Mean operative time (186 minutes) decreased with surgeon experience (p = 0.003) but was independent of tumor size (p = 0.964). Mean warm ischemia time (27.6 minutes) depended on tumor size (p = 0.005) but not on experience (0.964). Mean blood loss was 385 cc and the perioperative transfusion rate was 6.9%. Postoperative complications occurred in 23 cases (10.6%) with the most common being ileus (1.8%), bleeding (1.8%) and urinary leakage (1.4%). Although the mean serum creatinine change after LPN was a function of tumor size (p <0.001), it was clinically insignificant (0.13 mg/dl). No significant relationship was observed between warm ischemia time and creatinine change (p = 0.262). The final pathological evaluation revealed renal cell carcinoma in 144 patients (66.4%) and the overall positive margin rate was 3.5%. Only 2 renal cell carcinoma recurrences in the operated kidney (1.4%) were identified (mean followup +/- SD 24 +/- 12 months). CONCLUSIONS: LPN is an effective approach for treating small renal masses with low perioperative morbidity. Contrary to previous reports, more than 30% of the enhancing renal lesions excised in this series were found to be benign on final pathological evaluation.