Citations

689 Background: The role of antiangiogenic agents in advanced RCC is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. In this meta-analysis of 3 randomized control trials (RCTs), we sought to determine the efficacy of these agents in RCC patients who underwent nephrectomy with high risk of relapse. Methods: We searched three databases, including Pubmed, Embase, and Cochrane Central Register of Controlled Trials to identify RCTs comparing antiangiogenic agents to placebo in post-nephrectomy RCC patients. We evaluated: 1) the effect of antiangiogenics in highest risk groups as defined by individual studies; 2) the role of each agent separately; and 3) the effect in clear-cell RCC population. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random effects models Results: Three RCTs (N = 3693 patients) were identified. All studies were comparing placebo to antiangiogenics: sunitinib, sorafenib, and pazopanib. Overall, antiangiogenics did not improve DFS (HR 0.92, 95% CI 0.78 to 1.07) or OS (HR 0.99, 95% CI 0.79 to 1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire studied group for either DFS (HR 0.89, 95% CI 0.67 to 1.19) or OS (HR 1.11, 95% CI 0.90 to 1.37). In addition, when restricting the analysis to the high risk group, sunitinib did not show any advantage in terms of DFS (HR 0.85, 95% CI 0.67 to 1.07) and OS (HR 1.04, 95% CI 0.83 to 1.31). Conclusions: Based on the available evidence, antiangiogenics do not seem to add an advantage over placebo in terms of OS and DFS in high risk RCC patients after nephrectomy. Further studies are needed to identify the patient population which might derive a benefit from antiangiogenics in the adjuvant setting.

Background: A shorter sleep duration has been identified as a risk factor for cardiovascular diseases and increased mortality. It has been hypothesized that a short sleep duration may be linked to changes in ghrelin and leptin production, leading to an alteration of stress hormone production. Here, we conducted a systematic review and meta-analysis to investigate the potential relationship between a sleep duration and cardiovascular disease mortality. Methods: We conducted a comprehensive search of Ovid Medline In-Process and other non-indexed citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus from database inception to March 2017. Observational studies were included if the studies reported hazard ratios or odds ratios of the associations between sleep durations (short and long) and cardiovascular disease mortality. Data were extracted by a reviewer and then reviewed by two separate reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled hazard ratios and pooled odds ratios with 95% confidence intervals (CI). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. Results: In total, our meta-analysis included 19 studies (31 cohorts) with a total of 816,995 individuals with 42,870 cardiovascular disease mortality cases. In pooled analyses, both short (risk ratio 1.19; 95% CI 1.13 to 1.26, P<0.001, I2=30.7, Pheterogeneity=0.034), and long (risk ratio 1.37; 95% CI 1.23 to 1.52, P<0.001, I2=79.75, Pheterogeneity<0.001) sleep durations were associated with a greater risk of cardiovascular disease mortality. Conclusions: Both short (<7 hours) and long sleep durations (>9 hours) can increase the risk of overall cardiovascular disease mortality, particularly in Asian populations and elderly individuals. Future epidemiological studies would ideally include objective sleep measurements, rather than self-report measures, and all potential confounders, such as genetic variants.

Summary at a GlanceAs the population ages, large numbers of elderly patients will present with kidney diseases. Kidney biopsy for elderly patients is generally well tolerated and informative. Compared with younger adults, IgA nephropathy in the elderly carries a poor prognosis. In patients with intercurrent infections, IgA‐dominant postinfectious GN should be carefully differentiated from idiopathic IgA nephropathy. Existing ESRD and mortality prediction models/scoring systems for IgA nephropathy may not be generalized to elderly patients.

AbstractObjectiveThe aim of this study was to perform a systematic review and meta‐analyses of observational studies of transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve stenosis (BcAV).BackgroundTAVR for BcAV stenosis has been associated with an increased incidence of paravalvular leaks, valve malposition, pacemaker placement and all‐cause mortality. The conclusions drawn have been limited by small sample sizes. The use of TAVR for BcAV stenosis remains controversial.MethodsWe searched multiple databases from the inception of the databases through September 30, 2016 for studies of TAVR for BcAV stenosis. We included all observational studies with more than one patient and at least 1 month of outcomes.ResultsWe analyzed 13 observational studies with 758 patients. Meta analyses showed device success rate of 95% [95% confidence interval (CI) 90.2% to 98.5%] and an early safety event in 16.9% [95% CI 12.2% to 22%]. At 30 days, moderate to severe paravalvular leak was seen in 12.2% [95% CI 3.1% to 24.8%] and new pacemaker implantation in 17.9% [95% CI 14.2% to 22%]. All‐cause mortality was 3.7% [95% CI 2.1% to 5.6%], which should be viewed in the context of an STS PROM of 5.0%.ConclusionsThis analysis suggests that TAVR for BcAV is not associated with excess mortality. The incidence of paravalvular leaks and pacemaker implant is increased compared to tricuspid aortic valve cohorts undergoing TAVR, and operators should weigh these potential complications against the clinical benefit provided by TAVR for BcAV patients at high risk for surgical valve replacement.

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down‐staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow‐up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06‐1.85; I 2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060‐2.370; I 2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down‐staging therapy versus no downstaging, and this showed a significant increase in 1‐year (two studies, RR, 1.11; 95% CI, 1.01‐1.23) and 5‐year (1 study, RR, 1.17; 95% CI, 1.03‐1.32) post‐LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (H epatology 2018;67:381‐400).

BACKGROUNDThere are limited therapeutic options for treatment‐refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine‐based regimens. The authors performed a meta‐analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first‐line treatment progression in patients with PDAC.METHODSDifferent databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first‐line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared with FP. Outcomes of interest included overall survival (OS) and progression‐free survival (PFS).RESULTSFive studies with 895 patients were identified. Patients randomized to receive FPIRI/FPOX had a significantly improved PFS and a trend toward improved OS compared with those who received FP monotherapy. When comparing FPIRI with FP, there was an improvement in both PFS (hazard ratio, 0.64; 95% confidence interval, 0.47‐0.87; P = .005) and OS (hazard ratio, 0.70; 95% confidence interval, 0.55‐0.89; P = .004) in patients who received the combination. Conversely, FPOX produced only a modest improvement in PFS with no improvement in OS.CONCLUSIONSCombination chemotherapy with OX or various IRI formulations appears to improve PFS compared with single‐agent FP. FPIRI, but not FPOX, appears to confer an OS advantage. The combination of FP with irinotecan formulations appears to be the appropriate next line of treatment upon progression after gemcitabine‐based chemotherapy regimens. Cancer 2017;123:4680‐4686. © 2017 American Cancer Society.