Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Minimally Invasive Pancreaticoduodenectomy: What is the Best “Choice”? A Systematic Review and Network Meta-analysis of Non-randomized Comparative Studies

Background: Many mini-invasive pancreaticoduodenectomy (MIPD) techniques have been reported, but their advantages with respect to an open technique (OPD) and with respect to each other are unclear. Method: A systematic literature search of studies comparing different types of MIPD was carried out: laparoscopic-assisted (LAPD), totally robotic (TRPD), totally laparoscopic (TLPD) or totally laparoscopicârobotic assisted (TLPD-RA) to OPD. The primary endpoint was postoperative mortality. The secondary endpoints were intraoperative, postoperative and oncological outcomes. A network meta-analysis was designed to generate direct, indirect and mixed estimate effects, between different approaches, for each variable. The effects were reported as pairwise comparisons and hierarchical ranking as to each approach could be the best or the worst for each outcome, expressed by the surface under the cumulative ranking curve. Results: Twenty studies were identified, involving 2759 patients: 1813 OPDs, 81 LAPDs, 505 TRPDs, 224 TLPDs and 136 TLPD-RAs. No differences regarding postoperative mortality were found in pairwise comparison. The LAPD technique had a high probability of being the worst approach, while TRPD had a high probability of being one of the best. Regarding the secondary endpoints, OPD was the best regarding operative time and postoperative bleeding, but the worst regarding blood loss and wound infection. The TRPD or TLPD-RA techniques seemed to be the best for delayed gastric emptying, length of hospital stay, harvested lymph nodes and postoperative morbidity. The TLPD technique was often the worst approach, especially for overall and major complications, postoperative bleeding and biliary leak. Conclusion: The safest MIPDs are those involving a robotic system which seems to have a promising role in ameliorating the outcomes of OPD, especially when compared to a laparoscopic approach