All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes.

OBJECTIVE: This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS: RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS: Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS: All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

BACKGROUND: Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events. METHODS AND RESULTS: A cohort of Roux-en-Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated-measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan-Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events (P=0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42-0.82). Improvements of cardiovascular risk factors (eg, 10-year cardiovascular risk score, total cholesterol, high-density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. CONCLUSIONS: Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure.

Successful sperm extraction and live birth after radiation, androgen deprivation and surgical castration for treatment of metastatic prostate cancer.

Fertility preservation has become an important aspect of cancer treatment given the gonadotoxic effects of oncologic therapies. It is now considered standard of care to offer sperm banking to men undergoing treatment for primaries that affect young individuals. Less is known regarding fertility preservation of patients afflicted with prostate cancer. This cohort has progressively expanded and grown younger in the post-PSA era. Prostatectomy, radiation, chemotherapy and androgen blockade all pose unique challenges to the infertility specialist. Optimum management becomes even more uncertain for those men with metastatic prostate cancer. Most of these individuals will have received multiple forms of therapy, each carrying a distinct insult to the patient's reproductive potential. We describe a case of successful ex vivo sperm extraction and live birth in a patient previously treated with radiation and chronic androgen deprivation for metastatic prostate cancer. The presented case demonstrates that conception after radiation therapy and chronic androgen deprivation is feasible. We propose that fertility counselling and sperm cryopreservation should be considered for all prostate cancer patients. Additionally, for those individuals undergoing external beam radiotherapy, testicular shielding should be routinely offered in the event further family building is desired.

Preoperative use of incretins is associated with increased diabetes remission after RYGB surgery among patients taking insulin: a retrospective cohort analysis.

OBJECTIVE: The main goal of this study was to determine the effects of incretins on type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery for patients taking insulin. BACKGROUND: Type 2 diabetes is a chronic disease with potentially debilitating consequences. RYGB surgery is one of the few interventions that can remit T2D. Preoperative use of insulin, however, predisposes to significantly lower T2D remission rates. METHODS: A retrospective cohort of 690 T2D patients with at least 12 months follow-up and available electronic medical records was used to identify 37 T2D patients who were actively using a Glucagon-like peptide 1 (GLP-1) agonist in addition to another antidiabetic medication, during the preoperative period. RESULTS: Here, we report that use of insulin, along with other antidiabetic medications, significantly diminished overall T2D remission rates 14 months after RYGB surgery (9%) compared with patients not taking insulin (56%). Addition of the GLP-1 agonist, however, increased significantly T2D early remission rates (22%), compared with patients not taking the GLP-1 agonist (4%). Moreover, the 6-year remission rates were also significantly higher for the former group of patients. The GLP-1 agonist did not improve the remission rates of diabetic patients not taking insulin as part of their pharmacotherapy. CONCLUSIONS: Preoperative use of antidiabetic medication, coupled with an incretin agonist, could significantly improve the odds of T2D remission after RYGB surgery in patients also using insulin.

Fat-free weight prediction in morbidly obese females.

PURPOSE: Precise estimation of creatinine clearance in obese individuals relies on the appropriate assessment of lean body weight (LBW). Anthropometric methods of predicting LBW have not been validated in morbidly obese populations. PATIENTS AND METHODS: Using an existing dataset of anthropometric data for a female cohort with morbid obesity who had undergone measured FFW with dual energy absorptiometry, we evaluated the performance of five previously reported estimating equations for the prediction of LBW. Linear regression was used to derive a new LBW prediction formula and was then compared with the other formulae. RESULTS: Seventy females (mean [standard deviation] age, weight, and body mass index 43.0 [11.0] years, 128.1 [13.8] kg, and 48.3 [4.8] kg/m(2), respectively) were identified. LBW as estimated by the method of Garrow and Webster correlated well (r = 0.87) with measured mass while demonstrating the highest accuracy, best precision, and smallest bias (93%, 2.1 kg, and 2.9 kg, respectively; P < 0.0001 for all comparisons). The derived formula further improved bias, precision, and accuracy. CONCLUSION: Among females with morbid obesity, most previously reported estimating equations for LBW predicted FFW poorly. These findings have important clinical implications for the assessment of kidney function and for safe and effective drug dosing.

Obesity in the workplace: impact on cardiovascular disease, cost, and utilization of care.

BACKGROUND: In forecasting the future of cardiovascular disease (CVD), the American Heart Association calls for preventive strategies with particular attention to obesity. The association between obesity and CVD, including coronary artery disease (CAD) and diabetes, is well established. The rising prevalence of obesity in the workforce may have additional implications for employers and employees besides the demonstrated effects on absenteeism and workers' compensation. OBJECTIVE: This study was undertaken to determine the impact of population obesity on care utilization and cost of cardiovascular conditions such as hypertension, CAD, and cerebrovascular disease (or stroke) in a large US population of employees engaged in a major corporate wellness program. STUDY SAMPLE: Using data from a single large industrial employer across 29 geographically distinct worksites in the United States, 179,708 episodes of care from 2004 to 2007 for 10,853 employees were included. METHODS: The population-based economic impact of obesity was calculated on the basis of the frequency of episodes of care per 1000 employees and on the amount eligible for payment per episode of care in US dollars. Data were obtained from a wellness program databases, episode of illness inventories, and pharmacy and medical claims. High and low prevalence rates of obesity, by obesity quartile, were used to create linear mixed models to examine associations with disease outcomes, while controlling for correlation within each worksite. RESULTS: Worksites with a high rate of obesity (ie, in the fourth quartile) had 348.4 more episodes of care of any kind per 1000 employees (P <.001), 38.6 more hypertension episodes of care per 1000 employees (P <.001), and 2.5 more cerebrovascular disease episodes of care per 1000 employees (P = .017) compared with worksites in the lower 3 quartiles. A worksite in the fourth obesity rate quartile had $223 greater cost per any kind of episode (P <.001), $169 greater cost per hypertension episode (P = .003), and $1620 more per CAD episode (P = .005) compared with worksites in the lower 3 quartiles. The overall economic impact per 1000 employees was calculated by combining episode frequency and eligible amount for payment per episode. For sites in the lower 3 quartiles of obesity, the eligible amount per 1000 employees for any kind of care was $4.01 million. However, for sites in the highest obesity quartile, the eligible amount for payment per 1000 employees was $5.26 million. This translates into $1250 greater cost per employee. Similar calculations were used to evaluate the effect of obesity on the amount eligible for payment per employee for hypertension, CAD, and cerebrovascular disease episodes, with an estimated $69, $89, and $8 greater cost, respectively, per employee. CONCLUSION: Worksites with greater obesity prevalence rates were associated with numerically more frequent and more expensive episodes of care than worksites with low obesity prevalence.

Tracheal instillation of urban PM(2.5) suspension promotes acute cardiac polarization changes in rats.

The mechanisms by which PM(2.5) increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM(2.5) induces acute cardiac polarization alterations in healthy Wistar rats. PM(2.5) samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 microg PM(2.5) were administered by tracheal instillation. P wave duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.95 +/- 0.06, and 0.96 +/- 0.07; P < 0.001), and 50 microg (0.98 +/- 0.06, 0.98 +/- 0.07, and 0.96 +/- 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.98 +/- 0.07, and 0.97 +/- 0.08) and 50 microg (0.99 +/- 0.05, 0.97 +/- 0.0, and 0.95 +/- 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 microg (P < 0.001). QRS interval duration decreased at 20 and 50 microg in relation to blank filter solution and 10 microg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 microg (0.94 +/- 0.12, 0.88 +/- 0.14, and 0.88 +/- 0.11) and 50 microg (1.00 +/- 0.13; 0.97 +/- 0.11 and 0.98 +/- 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 microg (P < 0.001). PM(2.5) induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.

Tracheal instillation of urban PM2.5 suspension promotes acute cardiac polarization changes in rats

The mechanisms by which PM2.5 increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM2.5 induces acute cardiac polarization alterations in healthy Wistar rats. PM2.5 samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 µg PM2.5 were administered by tracheal instillation. P wave duration decreased significantly at 20 µg (0.99 ± 0.06, 0.95 ± 0.06, and 0.96 ± 0.07; P < 0.001), and 50 µg (0.98 ± 0.06, 0.98 ± 0.07, and 0.96 ± 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 µg (0.99 ± 0.06, 0.98 ± 0.07, and 0.97 ± 0.08) and 50 µg (0.99 ± 0.05, 0.97 ± 0.0, and 0.95 ± 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 µg (P < 0.001). QRS interval duration decreased at 20 and 50 µg in relation to blank filter solution and 10 µg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 µg (0.94 ± 0.12, 0.88 ± 0.14, and 0.88 ± 0.11) and 50 µg (1.00 ± 0.13; 0.97 ± 0.11 and 0.98 ± 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 µg (P < 0.001). PM2.5 induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.

Group cognitive training in old age: paper-and-pencil tasks of processing speed

Psychometric models attribute cognitive aging to decline in executive fuctions: processing speed(PS) or PS plus coordination of operations, both related to theprefrontal lobes. In a first study, healthy aged subjets (mean age: 68.42 years, range: 59-81; mean formalschooling: 6.47 years, range: 2-15) were divided into two groups. Group 1 (n=9) trained six VP paper-and-pencil tasks (letter and symbol recognizing speed) for five 1-hour daily sessions. Group 2 (n=8) received the same amount of training in a face-name association task. Measures of working memory employed in the pre-and post-tests were digit span, word span sentence comprehension. Group 1 improved significantly both in VP for letters and in the sentence comprehension measure. Group 2 improvement only in the paired associates learning task. Training old individuals on processing speed tasks may thus improve their working memory performance. In second training study, it was possible to assess coordination-related measures of working memory in the pre-and post-tests. Group 3 trained VP and was composed of 15 subjects with mean a age of 68.33 years (SD=6.36) and a mean formal schooling of 7.00 years (SD=3.22). Group 4, wich trained paired associates, consisted of 17 individuals with a mean age of 66.42 years (SD=8.38), who had a mean schooling of 7.77 years (SD=3.68). Contrary to our expectations, only training Group 4 exhibited generalization effects related to coordinatio of operations in working memory. These results confirm only partially unifactorial models of working memory

Small bowel morphology in British Indian and Afro-Caribbean subjects: evidence of tropical enteropathy.

Distal duodenal biopsy specimens taken from 30 white, 35 Indian, and 20 Afro-Caribbean residents of West Birmingham during routine endoscopy for dyspepsia, were assessed by dissecting microscopy and morphometry. Finger-shaped villi were significantly less frequent in the Indian and Afro-Caribbean subjects than in the white subjects when assessed by dissecting microscopy (p less than 0.005), and both immigrant groups had decreased mucosal thickness (p less than 0.01), villous height (p less than 0.001), villous:crypt ratios (p less than 0.01) and enterocyte height (p less than 0.05) compared with the white group. In the Indian subjects, villous height and villous:crypt ratios correlated significantly with the time since the last visit to the Indian subcontinent (p less than 0.005). Serum alkaline phosphatase values were significantly higher in the Indian subjects compared with the whites (p less than 0.02), and serum globulins were increased in both the Afro-Caribbean and Indian subjects (p less than 0.01). There were no correlations between morphometric indices and body habitus or biochemical or haematological indices and the long term effect of the morphological changes is not clear.

Small bowel morphology in British Indian and Afro Caribbean subjects: evidence of tropical enteropathy

Distal duodenal biopsy specimens taken from 30 white, 35 Indian, and 20 Afro-Caribbean residents of West Birmingham during routine endoscopy for dyspepsia, were assessed by disecting microscopy and morphometry. Finger-shaped villi were significantly less frequent in the Indian and Afro-Caribbean subjects than in the white subjects when assessed by disecting microscopy (p<0.005), and both immigrant groups had decreased mucosal thickness (p<0.01), villous height (p<0.001), villous:crypt ratios (p<0.01) and enterocyte height (p<0.05) compared with the white group. In the Indian subjects villous height and villous:crypt ratios correlated significantly with the time since the last visit to the Indian subcontinent (p<0.005). Serum alkaline phosphatase values were significantly higher in the Indian subjects compared with the white (p<0.02), and serum globulins were increased in both the Afro-Caribbean and Indian subjects (p<0.01). There were no correlations between morphometric indices and body habitus or biochemical or haematological indices and the long term effect of the morphological changes is not clear. (AU)