Factors influencing long-term weight loss after bariatric surgery.

BACKGROUND: Bariatric surgery provides sustained weight loss and improves comorbidities. However, long term data has shown that patients gradually regain weight after 1 year. Several factors have been associated with poor weight loss after bariatric surgery. OBJECTIVE: Our goal is to investigate factors associated with poor weight loss following laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). SETTING: Military academic medical center. METHODS: Retrospective review of 247 patients who underwent laparoscopic SG or RYGB between 2010-2012 at Eisenhower Army Medical Center and followed for 5 years postoperatively. Factors of age, type of surgery, sex, hypertension, depression, and type 2 diabetes (T2D) are analyzed in univariate and multivariate analysis with percent total weight loss (%TWL) and Body Mass Index (BMI) change as primary endpoints measured at 3 and 5 years. RESULTS: Average BMI change are maximized at 1 year and decreased at 3 and 5 years post-surgery. Age, diabetes, hypertension and type of surgery significantly influenced weight loss at 3 and 5 years on univariate analysis. However, patients with diabetes, hypertension and sleeve gastrectomy were significantly older than comparable control group. Multivariable analysis showed that age and type of surgery, not diabetes or hypertension, were associated with poor %TWL and BMI change at 3 and 5 years. CONCLUSION: While presence of hypertension and diabetes initially appeared to be associated with weight recidivism, their impacts were negligible on multivariable analysis. However, age and sleeve gastrectomy are independent risk factors. Our data can be used to counsel patients on expected weight loss after bariatric surgery.

Detection of intermediates in the oxidative half-reaction of the FAD-dependent thymidylate synthase from Thermotoga maritima: carbon transfer without covalent pyrimidine activation.

Thymidylate, a vital DNA precursor, is synthesized by thymidylate synthases (TSs). A second class of TSs, encoded by the thyX gene, is found in bacteria and a few other microbes and is especially widespread in anaerobes. TS encoded by thyX requires a flavin adenine dinucleotide prosthetic group for activity. In the oxidative half-reaction, the reduced flavin is oxidized by 2'-deoxyuridine 5'-monophosphate (dUMP) and (6R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate (CH2THF), synthesizing 2'-deoxythymidine 5'-monophosphate (dTMP). dTMP synthesis is a complex process, requiring the enzyme to promote carbon transfer, probably by increasing the nucleophilicity of dUMP and the electrophilicity of CH2THF, and reduction of the transferred carbon. The mechanism of the oxidative half-reaction was investigated by transient kinetics. Two intermediates were detected, the first by a change in the flavin absorbance spectrum in stopped-flow experiments and the second by the transient disappearance of deoxynucleotide in acid quenching experiments. The effects of substrate analogues and the behavior of mutated enzymes on these reactions lead to the conclusion that activation of dUMP does not occur through a Michael-like addition, the mechanism for the activation analogous with that of the flavin-independent TS. Rather, we propose that the nucleophilicity of dUMP is enhanced by electrostatic polarization upon binding to the active site. This conclusion rationalizes many of our observations, for instance, the markedly slower reactions when two arginine residues that hydrogen bond with the uracil moiety of dUMP were mutated to alanine. The activation of dUMP by polarization is consistent with the majority of the published data on ThyX and provides a testable mechanistic hypothesis.