In this section, we will highlight the key high-impact studies, updates, and analyses published in medicine during the past week.
Diabetic nephropathy is a leading cause of end-stage renal disease (ESRD). Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) are commonly used to decrease proteinuria. However, their safety and efficacy in combination for the slowing ESRD has not been thoroughly tested. In this randomized, controlled study, 1448 patients with type 2 diabetes, an estimated glomerular filtration rate (GFR) of 30.0 to 89.9, and urinary albumin-to-creatinine ratio > 300, were assigned to receive 100mg/d losartan and 10-40mg/d lisinopril or just 100mg/d losartan alone. The primary endpoint was the first occurrence of a change in estimated GFR, ESRD, or death. This study was stopped early because of safety concerns. There was no significant difference in the primary endpoint (hazard ration with combination therapy 0.88, 95% CI 0.70-1.12, P=0.30). There was likewise no benefit in mortality or cardiovascular events. However, combination therapy did increase the risk of hyperkalemia (6.3 events per 100 person-years vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Combination therapy using an ACE inhibitor and an ARB increased the risk of adverse events in patients with diabetic nephropathy.
Breast cancer patients who choose breast-conserving lumpectomy must currently be treated with adjuvant external beam radiation therapy (EBRT). However, receiving daily EBRT for periods of up to 6 weeks can be difficult and nearly impossible for some women who lack adequate healthcare access, thus making the breast-conserving treatment option non-viable. Targeted intraoperative radiotherapy (TARGIT) of the tumor bed is an alternative adjuvant treatment that would require fewer to no sessions of EBRT. In this randomized trial, 3451 women with invasive ductal carcinoma scheduled for lumpectomy were randomly assigned to receive adjuvant TARGIT or whole-breast EBRT. The 5-year risk for local recurrence for the TARGIT group was 3.3% (95% CI 2.1-5.1) versus 1.3% (95% CI 0.7-2.5) for EBRT (p = 0.042). Breast cancer mortality was 2.6% (95%Ci 1.5-4.3) in the TARGIT group versus 1.9% (95%CI 1.1-3.2) for the EBRT group (P = 0.56). Overall mortality rates were similar (3.9% (2.7–5.8) for TARGIT versus 5.3% (3.9–7.3) for EBRT (p=0.099)) attributable to fewer deaths from cardiovascular cases and other cancers in the TARGIT group. Lumpectomy with TARGIT should be considered an option for breast cancer management in certain patients.
Bariatric surgery is an increasingly used treatment for obese patients. It has been previously postulated that deficiencies in nutrients and calories after bariatic surgery may adversely affect fetal growth. In this matched cohort study conducted by the Swedish national health service, 2562 patients born to mothers with a history of bariatric surgery were matched with up to five control births by maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, educational level, and year of delivery. Investigators found that post-surgery births had a higher frequency of being preterm (9.7% vs. 6.1%, odds ratio 1.7, 95% CI 1.4-2.0, P<0.001). Post-bariatric surgery births were also more likely to be small for gestational age (5.2% vs. 3.0%, OR 2.0, 95% CI 1.5-2.5, P<0.001). There was no difference in rates of stillbirth or neonatal death. These differences held true when comparing births from women who underwent bariatric surgery to those who were eligible for bariatric surgery, thereby showing that bariatric surgery may increase the risk of preterm and small for gestational age births.
Autophagy pathways have been shown to be induced by exercise and are known to play a protective role in certain cancers and inflammatory disorders. They have also been found to be perturbed in Crohn’s disease through genome-wide association studies. In this cohort study, investigators examined the association between physical activity and risk of developing inflammatory bowel diseases (IBD) using data from the Nurses’ Health Study and Nurses’ Health Study II. The risk of developing Crohn’s disease was inversely associated with physical activity (P for trend 0.02). Women in the highest fifth of physical activity had a significantly lower risk of developing Crohn’s disease (hazard ratio 0.64, 95% CI 0.44-0.94). There was no association between physical activity and risk of ulcerative colitis (P for trend 0.46). This study therefore shows that in two large cohorts of US women, physical activity was inversely associated with risk of developing Crohn’s disease but not ulcerative colitis.
South Asian individuals have a much higher risk of developing type 2 diabetes in comparison to white Caucasians. This finding may be due to differences in the amount and activity of brown adipose tissue (BAT), which is believed to help combust fatty acids and glucose to produce heat. In this case-controlled observational study, 12 healthy, lean Dutch south Asian patients were matched with 12 Dutch Caucasian patients based on BMI and age. Investigators found that the south Asian patients had a lower thermoneutral resting energy expenditure (1297 kcal/day, SD 123 vs. 1689 kcal/day, SD 193, P=0.0008), higher shiver temperature (2.0 degrees higher, P=0.0067), lower non-shivering thermogenesis (decreased by 20%, P<0.0001), and lower BAT volume (188 mL, SD 81 vs. 287 mL, SD 169, P=0.04). BAT activity did not differ, as assessed by 18F-fluorodeoxyglucose uptake on PET CT scans. This study therefore shows that BAT volume and activity appears different in south Asian populations and may underlie their higher predisposition to metabolic disturbances.
By Neal Yuan and David Ouyang
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