Changes in telomere length 3-5 years after gastric bypass surgery.

Increased inflammation and oxidative stress associated with obesity can accelerate aging. Telomere length (TL) has the capacity to serve as an aging indicator at the cellular level. Obesity has a known association with shorter TL. This study evaluated TL of immune cells in a population of obese individuals who underwent gastric bypass surgery. Pre- and post-operative DNA samples were available for 50 subjects who had gastric bypass surgery. DNA was analyzed via quantitative polymerase chain reaction to determine TL. Changes in TL were evaluated by comparing TL at baseline to TL at 3-5 years post gastric bypass surgery. Sixty percent of the individuals in the study observed an increase in TL. Significant lengthening was observed for those with the shortest baseline TL (P=0.0011), but not for those with intermediate baseline TL (P=0.411) or longest baseline TL (P=0.207). Change in TL was negatively correlated with age and triglycerides but not correlated with weight loss induced by bariatric surgery. This study confirms that TL lengthening is observed post bariatric surgery and is the first to detect TL lengthening 3-5 years after surgery.

Electronically captured, patient-reported physical function: an important vital sign in obesity medicine.

OBJECTIVES: Impaired physical function (i.e., inability to walk 200 feet, climb a flight of stairs or perform activities of daily living) predicts poor clinical outcomes and adversely impacts medical and surgical weight management. However, routine assessment physical function is seldom performed clinically. The PROMIS Physical Function Short Form 20a (SF-20a) is a validated questionnaire for assessing patient reported physical function, which includes published T-score percentiles adjusted for gender, age and education. However, the effect that increasing levels of obesity has on these percentiles is unclear. We hypothesized that physical function would decline with increasing level of obesity independent of gender, age, education and comorbidity. MATERIALS AND METHODS: This study included 1,627 consecutive weight management patients [(mean ± SEM), 44.7 ± 0.3 years and 45.1 ± 0.2 kg/m2] that completed the PROMIS SF-20a during their initial consultation. We evaluated the association between obesity level and PROMIS T-score percentiles using multiple linear regression adjusting for gender, age, education and Charlson Comorbidity Index (CCI). RESULTS: Multiple linear regression T-score percentiles were lower in obesity class 2 (-12.4%tile, p < 0.0001), class 3 (-17.0%tile, p < 0.0001) and super obesity (-25.1%tile, p < 0.0001) compared to class 1 obesity. CONCLUSION: In patients referred for weight management, patient reported physical function was progressively lower in a dose-dependent fashion with increasing levels of obesity, independent of gender, age, education and CCI.

Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.

OBJECTIVE: The goal of the present study was to identify differences in gene expression between SAT, VAT and EAT depots in Class III severely obese individuals. DESIGN: Human subcutaneous (SAT) and visceral (VAT) adipose tissues exhibit differential gene expression profiles. There is little information, however, about the other proximal white adipose tissue, epigastric (EAT), in terms of its function and contribution to metabolism. SUBJECTS AND METHODS: Using RNA from adipose biospecimens obtained from Class III severely obese patients undergoing open Roux-en-Y gastric bypass surgery, we compared gene expression profiles between SAT, VAT and EAT, using microarrays validated by real-time quantitative PCR. RESULTS: The three depots were found to share 1907 genes. VAT had the greatest number of genes (66) expressed exclusively in this depot, followed by SAT (23), and then EAT (14). Moreover, VAT shared more genes with EAT (65) than with SAT (38). Further analyses using ratios of SAT/EAT, VAT/EAT and SAT/VAT identified specific as well as overlapping networks and pathways of genes representing dermatological diseases, inflammation, cell cycle and growth, cancer and development. Targeted analysis of genes, having a role in adipose tissue development and function, revealed that Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1-α) that regulates the precursor of the hormone Irisin (FNCD5) were abundantly expressed in all three fat depots, along with fibroblast growth factors (FGF) FGF1, FGF7 and FGF10, whereas, FGF19 and FGF21 were undetectable. CONCLUSIONS: These data indicate that EAT has more in common with VAT, suggesting similar metabolic potential. The human epigastric adipose depot could have a significant functional role in metabolic diseases and should be further investigated.

The effect of bi-level positive airway pressure on postoperative pulmonary function following gastric surgery for obesity.

The severely obese patient has varying degrees of intrinsic reduction of expiratory flow rates and lung volumes. Thus, the severely obese patient is predisposed to postoperative atelectasis, ineffective clearing of respiratory secretions, and other pulmonary complications. This study evaluated the effect of bi-level positive airway pressure (BiPAP) on pulmonary function in obese patients following open gastric bypass surgery Patients with a body mass index (BMI) of at least 40 kg/m2 who were undergoing elective gastric bypass were eligible to be randomized to receive either BiPAP during the first 24 h postoperatively or conventional postoperative care. Patients with significant cardiovascular and pulmonary diseases were excluded from the study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), peak expiratory flow rate (PEFR), and percent hemoglobin oxygen saturation (SpO2) were measured preoperatively, and on postoperative days 1, 2, and 3. Twenty-seven patients were entered in the study 14 received BiPAP and 13 received conventional postoperative care. There was no significant difference preoperatively between the study and control groups in regards to age, BMI, FVC, FEV1.0, PEFR or SpO2. Postoperatively expiratory flow was decreased in both groups. However, the FVC and FEV1.0 were significantly higher on each of the three consecutive postoperative days in the patients who received BiPAP therapy. The SpO2 was significantly decreased in the control group over the same time period. Prophylactic BiPAP during the first 12-24 h postoperatively resulted in significantly higher measures of pulmonary function in severely obese patients who had undergone elective gastric bypass surgery. These improved measures of pulmonary function, however, did not translate into fewer hospital days or a lower complication rate in our study population of otherwise healthy obese patients. Further study is necessary to determine if BiPAP therapy in the first 24 postoperative hours would be of benefit in severely obese patients with comorbid illnesses who have undergone elective gastric bypass.

Wound closure technique and acute wound complications in gastric surgery for morbid obesity: a prospective randomized trial.

BACKGROUND: During the past 10 years, numerous clinical studies have supported the use of continuous monofilament fascial closure after laparotomy. Because of the increased incidence of surgical-site infections and other acute wound complications in the morbidly obese, these patients are well suited for a study of technical factors that may affect the frequency of these wound complications. STUDY DESIGN: A prospective, randomized study of the midline fascial closure technique in gastric bariatric operations was conducted between 1991 and 1998 in 331 consecutive morbidly obese patients. At the time of closure of the upper midline laparotomy wound, the patients were randomized into two groups: Group I patients (n = 172) underwent continuous fascial closure and group II patients (n = 159) underwent interrupted fascial closure. All patients received prophylactic antibiotics in a similar fashion. Wounds were monitored for 30 days postoperatively, and acute wound complications were classified as superficial or deep. Superficial complications included superficial surgical-site infections, seromas, and hematomas. In all superficial complications, the fascia remained uninvolved and intact. Deep wound complications included deep surgical-site infections and fascial dehiscence. RESULTS: A total of 49 acute wound complications occurred (15%). There were 22 superficial (7%) and 27 deep (8%) wound complications in the 331 in the patients studied. Group I patients experienced fewer total wound complications than group II patients (18 versus 31; p=0.021). Group I patients also experienced fewer deep wound complications than group II (5 versus 22; p = 0.003). CONCLUSIONS: Continuous fascial closure reduces major acute wound complications in morbidly obese patients undergoing gastric operations for obesity.

Nonsurgical factors that influence the outcome of bariatric surgery: a review.

OBJECTIVE: Severe obesity (ie, at least 100% overweight or body mass index > or =40 kg/m2) is associated with significant morbidity and increased mortality. It is apparently becoming more common in this country. Conventional weight-loss treatments are usually ineffective for severe obesity and bariatric surgery is recommended as a treatment option. However, longitudinal data on the long-term outcome of bariatric surgery are sparse. Available data indicate that the outcome of bariatric surgery, although usually favorable in the short term, is variable and weight regain sometimes occurs at 2 years after surgery. The objective of this study is to present a review of the outcome of bariatric surgery in three areas: weight loss and improvement in health status, changes in eating behavior, and psychosocial adjustment. The study will also review how eating behavior, energy metabolism, and psychosocial functioning may affect the outcome of bariatric surgery. Suggestions for additional research in these areas are made. METHOD: Literature review. RESULTS: On average, most patients lose 60% of excess weight after gastric bypass and 40% after vertical banded gastroplasty. In about 30% of patients, weight regain occurs at 18 months to 2 years after surgery. Binge eating behavior, which is common among the morbidly obese, may recur after surgery and is associated with weight regain. Energy metabolism may affect the outcome of bariatric surgery, but it has not been systematically studied in this population. Presurgery psychosocial functioning does not seem to affect the outcome of surgery, and psychosocial outcome is generally encouraging over the short term, but there are reports of poor adjustment after weight loss, including alcohol abuse and suicide. CONCLUSIONS: Factors leading to poor outcome of bariatric surgery, such as binge eating and lowered energy metabolism, should be studied to improve patient selection and outcome. Long-term outcome data on psychosocial functioning are lacking. Longitudinal studies to examine the long-term outcome of bariatric surgery and the prognostic indicators are needed.

Eating disturbances and outcome of gastric bypass surgery: a pilot study.

OBJECTIVE: We examined how the outcome of gastric bypass surgery (GBP) was effected by the interaction between presurgery eating disturbance status and length of time since surgery. METHOD: Subjects were recruited from a list of patients who received GBP in the last 3 years. Twenty-seven patients 20.8 +/- 11.0 months postsurgery were interviewed. RESULTS: Both current eating disturbance status and weight regain were predicted by the interaction between presurgical eating disturbance status and length of time since surgery. The significant time period in this interaction was 2 years or more postsurgery. DISCUSSION: Patients with a presurgical eating disorder may experience a short-term improvement in their eating disorder following GBP that erodes on or after 2 years and is related to weight regain. Methods for improving surgical outcome in this population are discussed.

Nutritional support of the mechanically ventilated patient.

As with all critically ill patients, those requiring mechanical ventilation are susceptible to the wasting of illness and cannot survive without prompt nutritional support. It may be fair to say that the proper provision of nutrients, and in particular the avoidance of overfeeding, are even more crucial for this subset of critically ill patients. To maximize the overall benefits of feeding, it is crucial to provide the nutritional support early and enterally whenever possible. Therefore, the best strategy for early removal of the mechanical ventilatory support must include the timely and careful administration of nutrients, micronutrients, minerals, vitamins, and fluid, in conjunction with standard intensive care therapeutics and the appropriate respiratory muscle-strengthening program.

Safety and long-term efficacy of revisional surgery in severe obesity.

BACKGROUND: A National Institutes of Health Consensus Conference in 1991 established gastric surgery as accepted therapy for the treatment of severe obesity. The increasing prevalence of obesity in the United States, and the increasing numbers of patients undergoing gastric surgery for severe obesity, result in substantial numbers of patients being considered for revisional surgery. The indications and efficacy of revisional surgery remain controversial. METHODS: Sixty-three patients were followed prospectively after undergoing revisional surgery for obesity between 1981 and 1994. All patients had previously undergone obesity operations. Weight data were recorded at the time of original obesity surgery, at revisional surgery, and at most current follow-up. Complications following revisional surgery were monitored. RESULTS: The follow-up in the group is 98%. Revisional surgery after obesity surgery was associated with a 0% mortality rate and a serious complication rate of 16%. Body mass index (BMI) at the time of original surgery was 50 +/- 10 kg/m2, at revisional surgery 39 + 9 kg/m2, and at recent follow-up 34 +/- 10 kg/m2 (P < 0.001 vs original BMI). Those patients whose original BMI was > 50 kg/m2 lost significantly more weight (P < 0.0001) than those with an original BMI < 50 kg/m2. CONCLUSIONS: Revisional gastric surgery is safe and does provide patients with the opportunity to achieve long-term weight control.

The role of gastric surgery in the multidisciplinary management of severe obesity.

Severe obesity affects the health and quality of life of 4 million Americans. The major cost of treating severe obesity and its associated comorbidities of hypertension, diabetes, cardiovascular disease, pulmonary insufficiency, cancer, and degenerative arthritis as well as the poor long-term results of medical, drug, and behavioral therapy has increased the numbers of patients being referred for surgical treatment. Gastric bypass and vertical banded gastroplasty are the two procedures recommended for severely obese patients. These operations currently have low morbidity and mortality. Surgery should be considered adjuvant therapy and must be part of a multidisciplinary approach. The significant long-term weight control resulting from the surgical therapy is associated with improvement and, often, resolution of comorbidities, including diabetes, hypertension, hyperlipidemia, and pulmonary insufficiency.

Hemodynamic correlates of outcome in patients undergoing orthotopic liver transplantation. Evidence for early postoperative myocardial depression.

OBJECTIVE: To describe the hemodynamic and oxygen transport patterns in survivors and nonsurvivors following liver transplantation (LT) and to assess their relationship to organ failure and mortality. DESIGN: Retrospective cohort. SETTING: Surgical ICU in a tertiary care university teaching hospital. PATIENTS: Consecutive series of 113 adults undergoing LT between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or their records were incomplete (n = 7). MEASUREMENTS AND MAIN RESULTS: Preoperative severity of illness was assessed by the acute physiology and chronic health evaluation (APACHE) II scoring system. Hemodynamic and oxygen transport variables were recorded immediately preoperatively and sequentially every 12 h during the first 2 postoperative days. Organ failures (pulmonary, renal, cardiovascular, hepatic, and central nervous system) were assessed for patients in the postoperative period. Patients were grouped as survivors (n = 82) or nonsurvivors (n = 14) with a mortality rate of 15%. Preoperative APACHE II scores were significantly lower in survivors compared with nonsurvivors (7 +/- 0 vs 11 +/- 2; p = 0.029). Both preoperatively and postoperatively, survivors sustained a relatively higher mean arterial pressure, stroke volume index, left ventricular stroke work index, cardiac index, and oxygen delivery as compared with nonsurvivors (p < 0.01). The postoperative decline in systemic blood flow that was seen in both groups was particularly prominent in nonsurvivors during the first 12 h following LT (p < 0.03). Nonsurvivors sustained an approximately fivefold increase in the rate of organ failure (p < 0.0001); all patients (n = 6) with 4 or more organ failures died. CONCLUSION: Nonsurvivors of LT have less cardiac reserve pretransplant; postoperatively, they demonstrate early myocardial depression and subsequently lower levels of cardiac index and oxygen delivery. Patients who develop these hemodynamic patterns are more prone to organ failure and death.

A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients.

OBJECTIVE: To examine the safety and efficacy of multiple doses of PGG-glucan (poly-[1-6]-B-D-glucopyranosyl-[1-3]-B-D-glucopyranose) in high-risk patients undergoing major thoracic or abdominal surgery. DESIGN: An interventional, multicenter, double-blind, randomized, placebo-controlled study. SETTING: Four university-affiliated medical centers. PATIENTS: Sixty-seven high-risk patients undergoing major thoracic or abdominal surgery. INTERVENTION: Patients were randomized in a 1:1:1:1 ratio to receive saline placebo or PGG-glucan at a dose of 0.1 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or 2.0 mg/kg. One dose was administered before surgery and three doses were administered after surgery. MAIN OUTCOME MEASURES: To examine the safety and efficacy of PGG-glucan infusion and to identify potentially important factors for a planned phase III study. RESULTS: A dose-response trend with regard to infection incidence among patients who received PGG-glucan was observed. Serious infections occurred in four patients who received placebo and in three patients who received PGG-glucan at a dose of 0.1 mg/kg. However, only one patient who received PGG-glucan at a high dose had a serious infection. The incidence and severity of adverse events was comparable in all groups. CONCLUSIONS: PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation in a planned phase III trial.

Biosynthesis of 9-cis-retinoic acid from 9-cis-beta-carotene in human intestinal mucosa in vitro.

The role of 9-cis-beta-carotene (9-cis-beta-C) as a potential precursor of 9-cis-retinoic acid (9-cis-RA) has been examined in human intestinal mucosa in vitro. By using HPLC, uv spectra, and chemical derivatization analysis, both 9-cis-RA and all-trans-retinoic acid (all-trans-RA) have been identified in the postnuclear fraction of human intestinal mucosa after incubation with 9-cis-beta-C at 37 degrees C. The biosynthesis of both 9-cis-RA and all-trans-RA from 9-cis-beta-C was linear with increasing concentrations of 9-cis-beta-C (2-30 microM) and was linear with respect to tissue protein concentration up to 0.75 mg/ml. Retinoic acid was not detected when a boiled incubation mixture was incubated in the presence of 9-cis-beta-C. The rate of synthesis of 9-cis- and all-trans-RA from 4 microM 9-cis-beta-C were 16 +/- 1 and 18 +/- 2 pmol/hr/mg of protein, respectively. However, when 2 microM all-trans-beta-C was added to the 4 microM 9-cis-beta-C, the rate of all-trans-RA synthesis was increased to 38 +/- 6 pmol/hr/mg of protein, whereas the rate of 9-cis-RA synthesis remained the same. These results suggest that 9-cis-RA is produced directly from 9-cis-beta-C. Furthermore, incubations of either 0.1 microM 9-cis- or all-trans-retinal under the same incubation conditions showed that 9-cis-RA could also arise through oxidative conversion of 9-cis-retinal. Although only 9-cis-RA was detected when 9-cis-RA was used as the substrate, the isomerization of the all-trans-RA to 9-cis-RA cannot be ruled out, since both all-trans-RA and trace amounts of 9-cis-RA were detected when all-trans-retinal was incubated as the substrate. These data indicate that 9-cis-beta-C can be a source of 9-cis-RA in the human. This conversion may have a significance in the anticarcinogenic action of beta-C.

The oxygen cost of breathing may predict weaning from mechanical ventilation better than the respiratory rate to tidal volume ratio.

OBJECTIVE: To compare the respiratory rate to tidal volume ratio with the oxygen cost of breathing to see which could more accurately predict the outcome of ventilator weaning for surgical patients. DESIGN: Prospective comparison of two modalities used to predict the likelihood of successful ventilator weaning. PATIENTS: Twenty-eight consecutive patients with chronic respiratory insufficiency requiring long-term mechanical ventilation in the surgical intensive care unit at New England Deaconess Hospital, Boston, Mass, were studied. MAIN OUTCOME MEASURES: The oxygen cost of breathing and the respiratory rate to tidal volume ratio were measured during spontaneous breathing. Patients extubated within 2 weeks of being studied were designated as extubated while patients not extubated within this period or requiring reintubation were recorded as not extubated. RESULTS: The oxygen cost of breathing predicted successful extubation in all five patients who were extubated, and failure in 20 of 23 patients who could not be extubated (sensitivity, 100%; specificity, 87%). In contrast, the respiratory rate to tidal volume ratio predicted extubation for only two of five patients who were extubated and predicted failure in only 12 of 23 patients who could not be extubated (sensitivity, 40%; specificity, 52%). CONCLUSION: For this group of patients requiring prolonged ventilation, the oxygen cost of breathing proved to be a more reliable predictor of both successful extubation and failure.

Could the oxygen cost of breathing be used to optimize the application of pressure support ventilation?

Pressure support ventilation (PSV) is a new ventilator modality that augments spontaneous inspiratory pressure with selected levels of positive airway pressure. There is presently considerable interest in its use in the management of critically ill, ventilator-dependent patients. The optimal method for application has not yet been established. This study investigated the effects of PSV on the oxygen cost of breathing (OCOB), a clinically applicable technique for quantitating the work of breathing. The OCOB and other bedside variables of pulmonary function were measured during PSV in ventilator-dependent patients where weaning was limited by an inability to sustain respiratory work. Nine studies were performed in 8 patients in the surgical intensive care unit. The OCOB, tidal volume (VT), respiratory rate (RR), and minute ventilation (VE) were measured at various levels of pressure support. The OCOB was calculated from the difference in oxygen consumption (VO2) during mechanical and spontaneous ventilation both at CPAP and with PSV. With increasing levels of PSV, the OCOB was observed to steadily decrease from 22% to 8% (p < 0.001). There were also statistically significant increases in VT and decreases in RR. VE appeared not to be influenced. The results of this study suggest that the bedside measurement of the OCOB may be an accurate, simple, and reproducible method of titrating the level of applied pressure support in order to optimize respiratory work.

Patterns of recurrent colorectal cancer and recovery surgery.

In only two areas of colorectal cancer recurrence does surgery provide benefit. For a minority of patients with liver metastases that can be resected completely, cure is possible. Recent data from a prospective liver surgery protocol provide a perspective on the outcome, morbidity, and mortality of the procedure and confirm many of the suggestions in previous retrospective reviews. For patients with isolated pelvic or perineal recurrence, surgical removal of recurrent tumor provides palliation, but only if in-hospital convalescence is minimal and if recently introduced reconstructive techniques allow early rehabilitation.