Transoral outlet reduction with full thickness endoscopic suturing for weight regain after gastric bypass: a large multicenter international experience and meta-analysis.

BACKGROUND AND AIMS: Many patients who undergo bariatric surgery will experience weight regain and effective strategies are needed to help these patients. A dilated gastrojejunal anastomosis (GJA) has been associated with weight recidivism after Roux-en-Y gastric bypass surgery (RYGB). Endoscopic transoral outlet reduction (TORe) with a full thickness endoscopic suturing device (Overstitch, Apollo Endosurgery, Austin, TX) is a minimally invasive therapeutic option. The primary aim of this project was to examine the safety and long-term efficacy data from three bariatric surgery centers and to conduct a systematic review and meta-analysis of the existing literature. METHODS: Patients who underwent TORe with the Overstitch device from Jan 2013 to Nov 2016 at 3 participating bariatric surgery centers were included in the multicenter analysis. For the systematic review and meta-analysis, a comprehensive search of multiple English databases was conducted. Random effects model was used. RESULTS: 130 consecutive patients across three centers underwent TORe with an endolumenal suturing device. These patients (mean age 47; mean BMI 36.8) had experienced 24.6% weight regain from nadir weight after RYGB. Average weight lost at 6, 12, and 18 months after TORe was 9.31 ± 6.7 kg (N = 84), 7.75 ± 8.4  kg (N = 70), 8 ± 8.8 kg (N = 46) (p < 0.01 for all three time points), respectively. The meta-analysis included 330 patients. The pooled weight lost at 12 months was 8.4 kg (95% CI 6.5-10.3) with no significant heterogeneity across included studies (p = 0.07). Overall, 14% of patients experienced nausea, 18% had pain and 8% required a repeat EGD. No serious adverse events reported. CONCLUSION: When implemented as part of a multidisciplinary intervention, TORe using endolumenal suturing is safe, reproducible, and effective approach to manage weight recidivism after RYGB and should be utilized early in the management algorithm of these patients.

Predictors of macrovascular disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the importance of classic and nonclassic risk factors in the development of coronary artery disease (CAD) or cerebrovascular disease (CVD) in patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS: In this community-based, prospective cohort study, quantitative measurements for cholesterol, triglycerides (TGs), glucose, and lipoprotein(a) detected as a sinking pre-beta-lipoprotein band on electrophoresis were obtained from 1968 through 1982 from 449 patients who were free of CAD and CVD but had type 2 DM. Demographic data and covariables obtained were age, body mass index, duration of diabetes, sex, smoking, and hypertension. The relationship of individual continuous factors to the development of CAD and CVD as well as multivariate models were evaluated with use of the Cox proportional hazards model. The primary outcome was to determine which risk factors are associated with development of CAD or CVD in patients with type 2 DM. RESULTS: After a mean follow-up of 13 years, 216 CAD and 115 CVD events had developed. The hazard ratio estimates with 95% confidence intervals (CIs) for CAD after multivariate analysis were significant for age, 1.45 (95% CI, 1.27-1.67); fasting glucose levels at enrollment, 1.63 (95% CI, 1.17-2.25); smoking, 1.45 (95% CI, 1.10-1.91); and TGs, 1.49 (95% CI, 1.15-1.92). The hazard ratio estimates for CVD were significant for age, 1.95 (95% CI, 1.59-2.38); hypertension, 1.89 (95% CI, 1.30-2.74); fasting glucose levels at enrollment, 1.69 (95% CI, 1.06-2.70); and smoking, 1.57 (95% CI, 1.07-2.30). CONCLUSION: In diabetic patients, age, fasting glucose levels, smoking, and TG levels are independent risk factors for development of CAD events. Age, hypertension, glucose, and smoking predicted development of CVD events.

Genetic testing in medullary thyroid carcinoma syndromes: mutation types and clinical significance.

OBJECTIVE: To determine the types of mutations and the clinical significance of a specific genotype in familial medullary thyroid carcinoma (MTC) syndromes. DESIGN: We retrospectively and prospectively studied patients with MTC at a tertiary referral center. MATERIAL AND METHODS: The study cohort consisted of 348 affected patients and at-risk family members of MTC kindreds, including 33 multiple endocrine neoplasia type IIA (MEN IIA) kindreds with 165 members, 13 familial MTC alone (FMTC) kindreds (at least 4 affected members with MTC per kindred, without evidence of pheochromocytoma and hyperparathyroidism) with 108 members, 15 "other hereditary MTC" kindreds (2 or 3 affected members) with 42 members, and 33 individuals with sporadic MTC. An additional 53 subjects from the aforementioned MEN IIA kindreds who were clinically affected but not genetically tested were also included in an analysis of the relationship between genotype and phenotype. The presence of germline mutations in the RET proto-oncogene was studied by DNA sequence analysis of exons 10, 11, and 13. RESULTS: Germline RET mutations in exons 10 and 11 were identified in 32 of 33 MEN IIA kindreds (97%), 10 of 13 FMTC kindreds (77%), and 10 of 15 "other hereditary MTC" kindreds (67%). No mutations were identified in exon 13. No patient with sporadic MTC had a germline mutation. In MEN IIA, codon 634 was affected in 73% of the kindreds, whereas in FMTC, the main affected codon was codon 618 (54%). In MEN IIA, patients with codon 634 mutations had a higher risk of having C-cell disease, pheochromocytoma, and hyperparathyroidism than did those with other mutations (P < 0.05, P < 0.001, and P < 0.01, respectively). CONCLUSION: RET analysis is a reliable, practical, and cost-effective test in the screening of at-risk family members of MEN IIA and FMTC kindreds. In addition, RET analysis may be helpful in the follow-up of gene carriers and for the early detection of pheochromocytoma and hyperparathyroidism in patients with codon 634 mutations.

Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

OBJECTIVE: To determine whether patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) had evidence of increased homocysteine levels compared with non-CADASIL patients with ischemic stroke or transient ischemic attack. PATIENTS AND METHODS: We compared fasting plasma homocysteine levels and levels 6 hours after oral loading with methionine, 100 mg/kg, in non-CADASIL patients with ischemic stroke or transient ischemic attack and in patients with CADASIL. Prechallenge, postchallenge, and change in homocysteine levels between the 2 groups were compared with use of the Wilcoxon rank sum test. RESULTS: CADASIL and non-CADASIL groups were similar in age (mean, 48.8 vs. 46.5 years, respectively; 2-tailed t test, P=.56) and sex (men, 86% vs 59%; Fisher exact test, P=.12). The 59 patients in the CADASIL group had higher median plasma homocysteine levels compared with the 14 patients in the non-CADASIL group, both in the fasting state (12.0 vs 9.0 micromol/L; P=.03) and after methionine challenge (51.0 vs 34.0 micromol/L; P=.007). Median difference between homocysteine levels before and after methionine challenge was greater in the CADASIL group than in the non-CADASIL group (34.5 vs. 24.0 micromol/ L; P = .02). CONCLUSION: Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL.

Prospective evaluation of Roux-en-Y gastric bypass as primary operation for medically complicated obesity.

OBJECTIVE: To determine prospectively the results of Roux-en-Y gastric bypass (RYGB) used as the primary weight-reducing operation in patients with medically complicated ("morbid") obesity. The RYGB procedure combines the advantages of a restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high-energy liquids without requiring an externally reinforced (banded) stoma. PATIENTS AND METHODS: Between April 1987 and December 1998, a total of 191 consecutive patients with morbid obesity (median weight, 138 kg [range, 91-240 kg]; median body mass index, 49 kg/m2 [range, 36-74 kg/m2]), all of whom had directly weight-related morbidity, underwent RYGB and prospective follow-up. RESULTS: Hospital mortality was 0.5% (1/191), and hospital morbidity occurred in 10.5% (20/191). Good long-term weight loss was achieved, and patients adapted well to the required new eating habits. The mean +/- SD weight loss at 1 year after operation (113 patients) was 52 +/- 1 kg or 68% +/- 2% of initial excess body weight. By 3 years postoperatively (74 patients), weight loss was still 66% +/- 2% of excess body weight. Overall, 53 (72%) of 74 patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight 3 years after the operation. In addition, only 1 (1%) of 98 patients had persistent postoperative vomiting 1 or more times per week. CONCLUSION: We believe that RYGB is a safe, effective procedure for most patients with morbid obesity and thus may be the current procedure of choice in patients requiring bariatrics++ surgery for morbid obesity.

Protein metabolism in diabetes mellitus.

Insulin deficiency is a protein catabolic state. In vivo studies have shown that insulin enhances short-side-chain amino acid intracellular uptake, stimulates transcription and translation of RNA, increases the gene expression of albumin and other proteins and inhibits liver protein breakdown enzymes. In IDDM patients most of the whole-body protein turnover studies have shown that insulin deficiency increases protein breakdown and increases amino acid oxidation and that these effects are reversed by insulin treatment. Recent studies have demonstrated that a substantial increase in leucine transamination during insulin deprivation contributes to leucine catabolism in IDDM patients. Protein synthesis in the insulin-deprived state is also increased although to a lesser extent than protein breakdown, and this increased whole-body protein synthesis is reduced with an insulin infusion; thus the effects of insulin are largely mediated through its effects on protein breakdown. The metabolic derangements in diabetes frequently involve disturbances in substrates and hormones other than insulin. The observed effects of insulin deficiency in diabetic patients vary in different body compartments; most of the effects of insulin on protein synthesis appear to occur in non-muscular tissues especially in the splanchnic area. In addition, insulin has a differential effect on hepatic protein synthesis, i.e. inhibits fibrinogen synthesis and promotes albumin synthesis. Insulin's anticatabolic effect in IDDM patients is largely due to its inhibition of protein breakdown. The net protein anabolism due to insulin occurs largely in skeletal muscle. In patients with NIDDM these effects are not noted, presumably because of residual endogenous insulin secretion. In fact, treatments that result in improvement of glucose metabolism in obese NIDDM patients do not affect protein metabolism.

Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] levels have been associated with the presence of atherosclerotic disease. However, the results of prospective studies of Lp(a) and cardiovascular disease have been contradictory. METHODS AND RESULTS: From 1968 through 1982, lipoprotein analysis was performed in 11,335 Olmsted County residents. Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a) levels based on electrophoretic pattern. Lp(a) bands were scored from 0 (absent) to 3 (increased). A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a) determinations were followed up for 14 years for development of coronary artery disease (CAD) and cerebrovascular disease (CVD). During 131,330 person-years of follow-up, there were 1848 CAD events and 841 CVD events. Age, diabetes, hypertension, cholesterol, and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women. There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a) levels for men and women. For Lp(a) level 3, the hazard ratio was 1.9 (range, 1.3 to 2.9) in women and 1.6 (range, 1.0 to 2.5) in men. The adjusted hazard ratio for CVD showed an irregular association with Lp(a) levels in men and no association in women. CONCLUSIONS: In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years, Lp(a) was a significant predictor of risk of future CAD. Lp(a) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women.