Long-term efficacy and safety of proprotein convertase subtilisin/kexin 9 monoclonal antibodies: A meta-analysis of 11 randomized controlled trials.

BACKGROUND: Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVE: The purpose of this study was to assess the long-term efficacy and safety of PCSK9 antibodies. METHODS: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched for relevant studies. RESULTS: A total of 11 studies including 38,235 participants who were treated for at least 48 weeks were included in this meta-analysis. The results suggested that PCSK9 antibody treatment significantly decreased LDL-C levels (mean difference, -50.23% [95% confidence interval {CI}, -56.65% to -43.82%]) compared with no PCSK9 antibody treatment and also decreased other atherogenic lipid fractions. PCSK9 antibody treatment also elicited a significant reduction in cardiovascular event rates compared with no antibody treatment (relative risk [RR], 0.86 [95% CI, 0.81-0.92]). This reduction consisted of separate significant reductions in the rates of myocardial infarction (RR, 0.73 [95% CI, 0.65-0.82]), coronary revascularization (RR, 0.79 [95% CI, 0.73-0.87]), and stroke (RR, 0.81 [95% CI, 0.68-0.96]). There were no clear differences in the incidences of treatment-emergent adverse events (TEAEs), serious TEAEs, or TEAEs of interest between the 2 groups; moreover, no differences between the 2 groups were found for other laboratory parameters. CONCLUSION: PCSK9 antibodies have significant effects on reducing LDL-C levels and improve cardiovascular outcomes. These antibodies have a satisfactory safety profile, which suggests that they are suitable for use as a long-term treatment.

The effectiveness and safety of laparoscopic sleeve gastrectomy with different sizes of bougie calibration: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis was performed to compare the influence of different calibrating bougie sizes on clinical outcomes in laparoscopic sleeve gastrectomy (LSG) for patients with obesity. MATERIALS AND METHODS: A systematic review of the literature was performed using the key words: "laparoscopic sleeve gastrectomy", "bougie size", "calibration", "obesity", and "obese" for searches of electronic databases up to October 2017. Clinical characteristics such as, the percentage of excess weight loss (%EWL), overall complications, gastrointestinal leaks, gastroesophageal reflux disease (GERD) were pooled by meta-analysis. Stata 12.0 (Stata Corp, College Station, TX, USA) was used to perform the meta-analysis. RESULTS: Data were extracted from 11 original studies matching our inclusion criteria. In our review, the group of patients who had operations with thinner bougies had a greater %EWL (SMD 0.23, 95% CI 0.14-0.33, P < .001) than the group where larger diameters were used. Furthermore, no significant differences were found in the incidence of overall complications (OR 1.00, 95% CI 0.73-1.37, P = .978), postoperative gastrointestinal leaks (OR 0.91, 95% CI 0.67-1.24, P = .554), and GERD (OR 0.77, 95% CI 0.37-1.59, P = .476) between the two groups. A robust result could not be made about remission of comorbidities using differing diameter bougies due to insufficient data. CONCLUSIONS: Use of thinner diameter bougies in LSG was more effective in enabling weight loss and did not increase the risk of overall complications, gastrointestinal leaks or GERD compared with larger diameter bougies.

The lipid accumulation product is highly related to serum alanine aminotransferase level in male adults.

Studies confirm that the lipid accumulation product (LAP), which is based on the waist circumference and fasting serum triglycerides, is highly related to cardiovascular and metabolic diseases. Nonalcoholic fatty liver disease is a hepatic manifestation of metabolic syndrome and closely correlated with the alanine aminotransferase (ALT) elevation. Abdominal obesity and dyslipidemia are the important risk factors for nonalcoholic fatty liver disease. Our aim was to examine the correlation between the LAP and ALT in apparently healthy adults. We conducted a cross-sectional study of 587 adults. The blood pressure, anthropometric measurements, fasting and postload glucose, insulin, fasting lipid profile, and liver enzymes were measured. The LAP was calculated. For each gender, the subjects were divided into 3 groups according to the ALT level. The correlation between the LAP and ALT was analyzed. The LAP increased progressively across the ALT tertiles. A Pearson correlation analysis demonstrated that the LAP positively associated with the ALT in men and women (both P < .05) but independently related to the ALT only in men. Furthermore, after adjusting for the other confounding factors, the subjects in the upper quartile of LAP was 3.61 times more likely to show ALT elevation compared with those in the lower quartiles in men. In addition, in men, the LAP was considered as the best marker to predict increased ALT. Our findings suggested that the LAP was independently correlated with the ALT but only in men. The LAP was the main risk marker and might be superior to other variables in recognizing increased ALT.

The impact of family history of type 2 diabetes on pancreatic beta-cell function.

AIMS: To study the impact of genetic factor on pancreatic beta-cell function in the Chinese population. METHODS: 233 first-degree relatives of patients with type 2 diabetes (T2D) with no history of blood glucose abnormalities and their 190 spouses, who did not have a family history of T2D, underwent a 75-g oral glucose tolerance test (OGTT). Based upon the OGTT, these two groups were further divided into three subgroups, including groups with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and type 2 diabetes. Insulin resistance (IR) was evaluated using the homeostasis model assessment-IR (HOMA-IR), beta-cell function indices of basal and first-phase were measured by DI1 (HOMA-beta/HOMA-IR) and DI2 (DeltaI30/DeltaG30/HOMA-IR), respectively. RESULTS: Among the first-degree relatives and their spouses, the HOMA-IR was highest in the T2D group and lowest in the NGT group. However, the HOMA-beta, DI1 and DI2 declined significantly with progressive reductions in glucose tolerance (P<0.01 or 0.05). DI1 and DI2 of the NGT group of first-degree relatives (FNGT) were significantly lower than those of the spouse NGT (SNGT) group (P<0.05). DI1 and DI2 of the IGR of first-degree relatives (FIGR) group were significantly lower than those of the spouse IGR (SIGR) group. CONCLUSIONS: Defects in pancreatic beta-cell function exist in the first-degree relatives, who have different glucose tolerance statuses, of T2D patients. These defects are more profound in FNGT and FIGR when compared to their spouses in corresponding glucose tolerance subgroups. However, there is no difference in IR between the corresponding glucose tolerance subgroups of the first-degree relatives and their spouses. It suggests that the genetic factor possibly aggravates beta-cell lesion.