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.

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.

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.

Complications and management of implanted venous access catheters.

A totally implanted subclavian venous access system composed of a reservoir and silastic catheter was employed in 92 patients receiving infusion chemotherapy and/or hyperalimentation. The major catheter complication was subclavian or jugular vein thrombosis observed in 15 patients (16%). Thrombosis was observed in the ipsilateral subclavian or jugular vein surrounding the catheter without restricting function, except in two patients with thrombosis in the vein at the end of the catheter. Prophylaxis with low-dose Coumadin was effective in preventing thrombosis in high-risk patients as defined by a history of prior thrombosis. Streptokinase and/or heparin relieved the signs and symptoms of thrombosis, but clot dissolution or reversal of collateral flow was not observed. Explantation of the catheter was not necessary in all patients in that embolic complications of the thrombosis were not observed, and the system was retained and functioned in five patients in spite of the presence of thrombosis around the catheter. Other complications of the implanted system include "pocket" infection, catheter migration, and occlusion. Most complications may be managed without obligate catheter removal.

Heart disease and hypertension in severe obesity: the benefits of weight reduction.

Severe obesity is associated with abnormalities of cardiac structure and function. These include an increased cardiac workload and ventricular hypertrophy. Hypertension in combination with severe obesity seriously burdens the heart because the increased preload and afterload compound cardiac work. Weight reduction induced by gastric operations for severe obesity is associated with resolution of hypertension, reduction in ventricular wall thickness and cardiac chamber size, as well as improved systolic function. Additional data are needed to predict when in the course of development of obese cardiomyopathy the changes in contractile function become irreversible. Additionally, the impact of coronary artery disease on the progression of obese cardiomyopathy and the effects of surgical weight reduction on cardiac structure and function need to be further clarified. Studies of the association between obesity, its treatment, and modification of cardiovascular risk are a major focus of preventive cardiology today.

Pulmonary complications of orthotopic liver transplantation.

Pulmonary complications following orthotopic liver transplantation (OLT) were prospectively evaluated in 18 individuals transplanted at the New England Deaconess Hospital. Of sixteen patients who survived the immediate postoperative period, 12 (75%) sustained a pulmonary complication. Of these complications, 64% were noninfectious--whereas 22% were infectious, and 14% probably infectious. Six of eight documented infections were caused by viruses of the herpes group. In four cases of viral pneumonitis other pulmonary pathogens were isolated (fungi-3, protozoan-1, bacteria-1). Unlike noninfectious complications, pulmonary infections were associated with a fatal outcome in five of six patients who died after OLT. Pulmonary complications are frequent and serious occurrences after OLT, and contribute to both the morbidity and mortality of this procedure. Compared with pulmonary complications seen after transplantation of other organs, OLT was associated with a higher proportion of noninfectious complications but a similar spectrum of pulmonary infections.

Left ventricular filling abnormalities in asymptomatic morbid obesity.

Indexes of left ventricular (LV) diastolic filling were measured by pulse Doppler echocardiography in 16 asymptomatic morbidity obese patients presenting for bariatric surgery and were compared with an age- and sex-matched lean control population. No patient had concomitant disorders known to affect diastolic function. All patients had normal systolic function. LV wall thickness and internal dimension were measured in order to calculate LV mass. Fifty percent of morbidly obese patients had LV diastolic filling abnormalities as assessed by the presence of greater than or equal to 2 abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in obese compared with control patients (1.16 +/- 0.26 vs 1.66 +/- 0.30, p less than 0.001). The peak velocity of early LV diastolic filling was significantly reduced in obese patients (75 +/- 15 vs 98 +/- 19 cm/s, p less than 0.001). The atrial contribution to stroke velocity as assessed by the time-velocity integral of late compared with total LV diastolic filling was significantly increased in obese patients (36 +/- 7 vs 27 +/- 4%, p less than 0.001). Obese patients had significantly increased LV mass (214 +/- 45 vs 138 +/- 37 g, p less than 0.001), even when corrected for body surface area (95 +/- 16 vs 76 +/- 16 g/m2, p less than 0.002). However, increased LV mass did not correlate with indexes of abnormal diastolic filling in obese patients. These data suggest that abnormalities of diastolic function occur frequently in asymptomatic morbidly obese patients and may represent a subclinical form of cardiomyopathy in the obese patient.

Intra-aortic balloon counterpulsation support in the high-risk cardiac patient undergoing urgent noncardiac surgery.

Patients with a recent myocardial infarction, congestive heart failure, sever angina, or uncorrected multivessel coronary artery disease are at increased risk of cardiac complications after major noncardiac surgery. Although invasive hemodynamic monitoring and preoperative optimization of cardiac status may lead to some reduction in the rate of perioperative cardiac events, the mortality from such events remains high. We report our experience with the use of perioperative intra-aortic balloon counterpulsation in eight patients with unstable coronary syndromes or severe coronary artery disease who underwent urgent noncardiac surgery. There were no perioperative cardiac events while the intra-aortic balloon pump (IABP) was in place. There were two postoperative cardiac events (non-fatal myocardial infarction, congestive heart failure) in the first postoperative week after the IABP was removed. One patient required emergent femoral thrombectomy as a result of intra-aortic balloon counterpulsation and subsequently died of a gastrointestinal hemorrhage. Intra-aortic balloon counterpulsation should be considered as an adjunct to maintain hemodynamic stability for the high-risk cardiac patient about to undergo urgent or emergent noncardiac surgery.

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.

Nutritional support in cardiac cachexia.

A nutritional survey of 350 hospital patients reveals 50 with cardiac disease who had clinically significant protein-calorie malnutrition. Assessment criteria of malnutrition (per cent normal) included triceps skin fold (52 per cent), arm muscle circumference (88 per cent), and impaired delayed hypersensitivity skin testing (i.e., deficiency in cell-mediated immunity), the latter frequently observed in patients with concurrent weight loss. The functional category of cardiac status was not precise in predictin the morbidity and mortality of 14 patients undergoing cardiac valvuloplasty. By contrast, a nutritional/metabolic profile using weight loss, triceps skin fold (35 per cent), arm muscle circumference (27 per cent), and cell-mediated immunity (29 per cent) did identify high-risk patients who could be expected to benefit by concurrent nutritional support (4/4). Further studies are indicated to determine if nutritional support for cardiac cachexia can reduce the levels of morbidity and mortality during mitral and tricuspid valve surgery.

Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications.

The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU.

Proteolysis associated with a deficit of peripheral energy fuel substrates in septic man.

Sixteen seriously septic patients were studied to determine whether proteolysis occurred to satisfy a deficit of peripheral fuel, as suggested by out previous experimental observations. Concentrations of glucose, lactate, free fatty acids,and alanine were measured in blood samples from the femoral artery and vein to determine extraction (+) and release (-) by the leg. Simultaneously, cardiac index (CI) was determined by thermal dilution, so that an estimate of uptake or production of fuel substrates could be made from the proportional relationship of cardiac index to peripheral blood flow. Due to the antilipolytic effect of elevated levels of insulin (42 +/- 4 muM per milliliter) in those patients with elevated cardiac indices (4.38 +/- 0.33 L. per square meter per minute), free fatty acid uptake (-0.59 +/- 0.021 mM.) was reduced. In low-flow septic shock (CI, 1.66 +/- .41 L. per square meter per minute), the majority of glucose taken up by the limb was converted to lactate (arterial lactate, 3.14 +/- 0.7 mM.; deltaA-V 0.68 +/- 0.17). Free fatty acid uptake also was impaired in low-flow sepsis. As opposed to fasting, arterial levels and uptake of ketone bodies were insignificant in sepsis. These findings suggest that there is a deficit of peripheral fuel with respect to glucose and fat. That protein is oxidized to fill this deficit is substantiated by the increased alanine release (-0.13 +/- 0.01, -0.33 +/- 0.12 mM.) in the high-flow and low-flow septic groups, respectively, whereas alanine production was three- and fourfold greater than that observed in fasting patients. Enhanced release of alanine reflects the magnitude of oxidation of branched-chain amino acids and accounts for the high rates of gluconeogenesis and proteolysis observed in sepsis.

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.

Management of recurrent pelvic tumors.

The management of regional tumor recurrence in the pelvis traditionally has been a difficult problem for surgeons and oncologists. The only meaningful therapy for these patients is a potentially curative re-resection. The records and operative reports of 29 patients with regional pelvic tumor recurrence treated between 1981 and 1986 were reviewed. The operative procedures performed included three bowel resections, six abdominoperineal resections, eight pelvic exenterations, eight resections of tumor recurrence, and four conservative procedures. There was one operative death in this group. Significant morbidity was noted in the group but was clustered in a small number of patients operated on early in the series. The median follow-up in this series was 13 months (range, two to 51 months). Nineteen (65%) of the patients are surviving at a median follow-up of ten months (range, two to 51 months). The median survival (following resection) in the ten patients (35%) who died was 18 months. In 15 (52%) of the patients, a complete resection was performed. In this group, the survival is 80% with a median follow-up of 11 months. Seven (37%) are surviving with no evidence of disease. Palliation of symptoms occurred in 23 (79%) of the 29 patients. Radical resection of tumor recurrence in the pelvis can be performed with acceptable mortality and complication rates. This therapy should be considered for further clinical trials combining surgical and adjuvant therapy in patients with regional pelvic tumor recurrence.

Management of the urinary tract involved by recurrent cancer.

We present our experience from 1982 to the present in treating 33 patients with recurrent cancers (colorectal, 22; gynecologic, six; breast, two; melanoma, two; and lung, one) secondarily involving the genitourinary tract. All patients had severe symptoms that required palliation. Endoscopically placed stents relieved ureteral obstruction in 18 (75%) of 24 patients with widespread metastatic disease. Two patients required percutaneous nephrostomy tubes, and five required open operations. Good to excellent palliation was achieved in 23 of 24 patients. Mean survival in the group with diffuse metastases was 13 months (range, six to 29 months). Nine patients with localized recurrences underwent surgical procedures. For localized pelvic recurrences, total exenteration (with or without intraoperative radiotherapy) provided excellent palliation with low morbidity. At the time of this report, five of six such patients had no evidence of disease, and one had a small asymptomatic pelvic recurrence, with a mean follow-up of 13 months (range, five to 19 months).

Albumin supplementation in the critically ill. A prospective, randomized trial.

Albumin replacement to correct hypoalbuminemia in critically ill patients has been controversial. This study was a prospective, randomized trial of 25% albumin administration in 40 hypoalbuminemic (serum albumin, less than 25 g/L [2.5 g/dL]), critically ill patients. The treatment group (18 patients) received 25% albumin supplementation to achieve and maintain serum albumin levels of 25 g/L (2.5 g/dL) or greater, while the nontreatment group (22 patients) received no concentrated albumin. There was no clinical benefit from albumin therapy when assessing mortality (39% vs 27%, treatment vs control) or major complication rate (89% vs 77% of patients). There were also no significant differences in length of hospital stay, intensive care unit stay, ventilator dependence, or tolerance of enteral feeding, despite significant elevations of albumin in the treatment group. The costly use of exogenous albumin as treatment for hypoalbuminemia in this patient population does not appear to be justified.

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.

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.

Acyclovir-associated fever: a case report.

Drug-induced fever has been associated with many agents. We treated a patient who developed high, spiking fevers while receiving intravenous acyclovir. Rechallenge with the drug was not attempted. Clinicians should be aware of the possibility of drug-induced fever in patients who receive systemic acyclovir.