Eric J. DeMaria

Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group.

OBJECTIVE To determine the therapeutic efficacy and safety of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in the treatment of patients with severe sepsis. DESIGN Prospective, randomized, double-blind, placebo-controlled, multicenter trial with a planned, midstudy, interim analysis. SETTING Ninety-one academic medical center intensive care units in North America and Europe. PATIENTS Patients with severe sepsis or septic shock (n = 696) received standard supportive care and antimicrobial therapy for sepsis, in addition to rhIL-1ra or placebo. INTERVENTIONS Patients were randomized to receive either rhIL-1ra (100 mg) or placebo (vehicle) by intravenous bolus, followed by a 72-hr continuous intravenous infusion of either rhIL-1ra (2.0 mg/kg/hr) or placebo. MEASUREMENTS AND MAIN RESULTS The study was terminated after an interim analysis found that it was unlikely that the primary efficacy end points would be met. The 28-day, all-cause mortality rate was 33.1% (116/350) in the rhIL-1ra treatment group, while the mortality rate in the placebo group was 36.4% (126/346), yielding a 9% reduction in mortality rate (p = .36). The patients were well matched at the time of study entry; 52.9% of placebo-treated patients were in shock while 50.9% of rhIL-1ra-treated patients were in shock at the time of study entry (p = .30). The mortality rate did not significantly differ between treatment groups when analyzed on the basis of site of infection, infecting microorganism, presence of bacteremia, shock, organ dysfunction, or predicted risk of mortality at the time of study entry. No excess number of adverse reactions or microbial superinfections were attributable to rhIL-1ra treatment in this study. CONCLUSIONS A 72-hr, continuous intravenous infusion of rhIL-1ra failed to demonstrate a statistically significant reduction in mortality when compared with standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has any therapeutic activity in severe sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.

Results of 281 Consecutive Total Laparoscopic Roux-en-Y Gastric Bypasses to Treat Morbid Obesity

ObjectiveTo determine the safety and efficacy of laparoscopic Roux-en-Y gastric bypass for the treatment of morbid obesity. Summary Background DataLaparoscopic Roux-en-Y gastric bypass is a new and technically challenging surgical procedure that requires careful study. MethodsThe authors attempted total laparoscopic Roux-en-Y gastric bypass in 281 consecutive patients. Procedures included 175 proximal bypasses, 12 long-limb bypasses, and 9 revisional procedures from previous bariatric operations. The gastrojejunostomy and jejunojejunostomy were primarily constructed using linear stapling techniques. ResultsEight patients required conversion to an open procedure (2.8%). The mean age of the patients was 41.6 years (range 15–71) and 87% were female. The mean preoperative body mass index was 48.1 kg/m2. The operative time decreased significantly from 234 ± 77 minutes in the first quartile to 162 ± 42 minutes in the most recent quartile. Postoperative length of stay averaged 4 days (range 2–91), with 75% of patients discharged within 3 days. The median hospital stay was 2 days. No patient died after surgery. Complications included three (1.5%) major wound infections (each followed a reoperation for a complication or open conversion), incisional hernia in 5 patients (1.8%), and anastomotic leak with peritonitis in 14 patients (5.1%). Three gastrojejunal leaks were managed without surgery, four by laparoscopic repair/drainage, and three by open repair/drainage. Only three patients had anastomotic leaks in the most recent 164 procedures (1.8%) since the routine use of a two-layer anastomotic technique. Data at 1 year after surgery were available in 69 of 96 (72%) patients (excludes revisions). Weight loss at one year was 70 ± 5% of excess weight. Most comorbid conditions resolved by 1 year after surgery; notably, 88% of patients with diabetes no longer required medications. ConclusionsLaparoscopic gastric bypass demonstrates excellent weight loss and resolution of comorbidities with a low complication rate. The learning curve is evident: operative time and leaks decreased with experience and improved techniques. The primary advantage is an extremely low risk of wound complications, including infection and hernia.

Greater risk of incisional hernia with morbidly obese than steroid-dependent patients and low recurrence with prefascial polypropylene mesh

BACKGROUND Incisional hernia is a serious complication of abdominal surgery. We compared incisional hernia frequency following gastric bypass (GBP) for morbid obesity versus total abdominal colectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. A prefascial polypropylene mesh repair was also evaluated. PATIENTS AND METHODS All patients had midline incisions, xiphoid to umbilicus in GBP patients and midepigastrium to pubis in IPAA patients. Fascia were closed with running No. 2 polyglycolic acid suture. Ninety-eight patients underwent prefascial polypropylene mesh repair; 80 were GBP patients, 46 had 1 previous repair, and 17 had 2 to 9 previous repairs (6 with properitoneal mesh). RESULTS Incisional hernia occurred in 20% (198/968) of GBP patients (19% without versus 41% with a previous hernia, P < 0.001) versus 4% (7/171) of the IPAA patients (P < 0.001), of whom 102 (60%) were taking prednisone (32 +/- 2 mg/d) and 5 were quite obese (body mass index > or = 30 kg/m2). Additional risk factors for hernia in GBP patients included wound infection, diabetes, sleep apnea, and obesity hypoventilation. For the 98 patients who underwent prefascial polypropylene mesh repair, the mean follow-up was 20 +/- 2 months (range 6 to 104), and complications occurred in 35% of patients, including minor wound infection (12%), major wound infection (5%), seroma (5%), hematoma (3%), chronic pain (6%), and recurrent hernia (4%). CONCLUSIONS Severe obesity is a greater risk factor for incisional hernia and hernia recurrence than chronic steroid use in nonobese colitis patients. A prefascial polypropylene mesh repair minimizes recurrence.

Bariatric Surgery for Severely Obese Adolescents

A 1991 National Institutes of Health Consensus Conference concluded that severely obese adults could be eligible for bariatric surgery if they had a body mass index (BMI) ≥35 kg/m2 with or ≥40 kg/m2 without obesity comorbidity. It was thought at that time that there were inadequate data to support bariatric surgery in severely obese adolescents. An estimated 25% of children in the United States are obese, a number that has doubled over a 30-year period. Very little information has been published on the subject of obesity surgery in adolescents. Therefore we reviewed our 20-year database on bariatric surgery in adolescents. Severely obese adolescents, ranging from 12 to less than 18 years of age, were considered eligible for bariatric surgery according to the National Institutes of Health adult criteria. Gastroplasty was the procedure of choice in the initial 3 years of the study followed by gastric bypass, which was found to be significantly more effective for weight loss in adults. Distal gastric bypass (D-GBP) was used in extremely obese patients (BMI ≥60 kg/m2) before 1992 and long-limb gastric bypass (LL-GBP) was used for super-obese patients (BMI ≥50 kg/m2) after 1992. Laparoscopic gastric bypass was used after 2000. Thirty-three adolescents (27 white, 6 black; 19 females, 14 males) underwent the following bariatric operations between 1981 and June 2001: horizontal gastroplasty in one, vertical banded gastroplasty in two, standard gastric bypass in 17 (2 laparoscopic), LL-GBP in 10, and D-GBP in three. Mean BMI was 52 ±11 kg/m2 (range 38 to 91 kg/m2), and mean age was 16 ± 1 years (range 12.4 to 17.9 years). Preoperative comorbid conditions included the following: type II diabetes mellitus in two patients, hypertension in 11, pseudotumor cerebri in three, gastroesophageal reflux in five, sleep apnea in six, urinary incontinence in two, polycystic ovary syndrome in one, asthma in one, and degenerative joint disease in 11. There were no operative deaths or anastomotic leaks. Early complications included pulmonary embolism in one patient, major wound infection in one, minor wound infections in four, stomal stenoses (endoscopically dilated) in three, and marginal ulcers (medically treated) in four. Late complications included small bowel obstruction in one and incisional hernias in six patients. There were two late sudden deaths (2 years and 6 years postop-eratively), but these were unlikely to have been caused by the bariatric surgical procedure. Revision procedures included one D-GBP to gastric bypass for malnutrition and one gastric bypass to LL-GBP for inadequate weight loss. Regain of most or all of the lost weight was seen in five patients at 5 to 10 years after surgery; however, significant weight loss was maintained in the remaining patients for up to 14 years after surgery. Comorbid conditions resolved at 1 year with the exception of hypertension in two patients, gastroesophageal reflux in two, and degenerative joint disease in seven. Self-image was greatly enhanced; eight patients have married and have children, five patients have completed college, and one patient is currently in college. Severe obesity is increasing rapidly in adolescents and is associated with significant comorbidity and social stigmatization. Bariatric surgery in adolescents is safe and is associated with significant weight loss, correction of obesity comorbidity, and improved self-image and socialization. These data strongly support obesity surgery for those unfortunate individuals who may have difficulty obtaining insurance coverage based on the 1991 National Institutes of Health Consensus Conference statement.

High Failure Rate After Laparoscopic Adjustable Silicone Gastric Banding for Treatment of Morbid Obesity

ObjectiveTo report the results from one of the eight original U.S. centers performing laparoscopic adjustable silicone gastric banding (LASGB), a new minimally invasive surgical technique for treatment of morbid obesity. Summary Background DataLaparoscopic adjustable silicone gastric banding is under evaluation by the Food & Drug Administration in the United States in an initial cohort of 300 patients. MethodsOf 37 patients undergoing laparoscopic placement of the LASGB device, successful placement occurred in 36 from March 1996 to May 1998. Patients have been followed up for up to 4 years. ResultsFive patients (14%) have been lost to follow-up for more than 2 years but at last available follow-up (3–18 months after surgery) had achieved only 18% (range 5–38%) excess weight loss. African American patients had poor weight loss after LASGB compared with whites. The LASGB devices were removed in 15 (41%) patients 10 days to 42 months after surgery. Four patients underwent simple removal; 11 were converted to gastric bypass. The most common reason for removal was inadequate weight loss in the presence of a functioning band. The primary reasons for removal in others were infection, leakage from the inflatable silicone ring causing inadequate weight loss, or band slippage. The patients with band slippage had concomitant poor weight loss. Bands were removed in two others as a result of symptoms related to esophageal dilatation. In 18 of 25 patients (71%) who underwent preoperative and long-term postoperative contrast evaluation, a significantly increased esophageal diameter developed; of these, 13 (72%) had prominent dysphagia, vomiting, or reflux symptoms. Of the remaining 21 patients with bands, 8 currently desire removal and conversion to gastric bypass for inadequate weight loss. Six of the remaining patients have persistent morbid obesity at least 2 years after surgery but refuse to undergo further surgery or claim to be satisfied with the results. Overall, only four patients achieved a body-mass index of less than 35 and/or at least a 50% reduction in excess weight. Thus, the overall need for band removal and conversion to GBP in this series will ultimately exceed 50%. ConclusionsThe authors did not find LASGB to be an effective procedure for the surgical treatment of morbid obesity. Complications after LASGB include esophageal dilatation, band leakage, infection, erosion, and slippage. Inadequate weight loss is common, particularly in African American patients. More study is required to determine the long-term efficacy of the LASGB

Multivariate Analysis of Risk Factors for Death Following Gastric Bypass for Treatment of Morbid Obesity

Objective:To identify the factors that increase mortality for either open or laparoscopic Roux-en-Y gastric bypass. Summary Background Data:Perioperative mortality is the most feared outcome of bariatric surgery, reported to occur in between 0.5% and 1.5% of patients. Methods:The bariatric database at Virginia Commonwealth University was queried for patients who had undergone either an open gastric bypass (O-GBP) or a laparoscopic gastric bypass (L-GBP). A multivariate logistic regression analysis to identify factors related to perioperative mortality was performed. Factors examined included age, gender, body mass index, preoperative weight, hypertension, diabetes mellitus, sleep apnea, obesity hypoventilation syndrome, venous stasis ulcers, intestinal leak, small bowel obstruction, and pulmonary embolus. Results:Since 1992, more than 2000 patients had either an O-GBP (n = 1431) or a L-GBP (n = 580). Of the O-GBP, 547 patients had a proximal GBP (P-GBP) and 884 superobese (body mass index > 50 kg/m2) patients had a long-limb GBP (LL-GBP). The differences in patient demographics, complications, and perioperative mortality rates between L-GBP and O-GBP and P-GBP and LL-GBP patients were examined. Overall, the independent risk factors associated with perioperative death included leak, pulmonary embolus, preoperative weight, and hypertension. Conclusions:The risk factors for perioperative death can be separated into patient characteristics and complications. The access method, open versus laparoscopic, was not independently predictive of death, but the operation type, proximal versus long limb, was predictive. The data do not suggest that superobese patients should not undergo surgery, as they are high risk for early death due to their body weight and comorbidities without surgery. Surgery should not be reserved as a desperate last measure for weight loss.

Experience with over 3,000 open and laparoscopic bariatric procedures: Multivariate analysis of factors related to leak and resultant mortality

Background: Intestinal leak is a potentially lethal complication of Roux en-Y gastric bypass (GBP). Identification of patients at high risk for leak may reduce complication rates of surgeons early in the procedure learning curve. Methods: A total of 3073 patients who underwent GBP were analyzed using univariate and multivariate logistic regression analyses of the following preoperative factors: hypertension (HTN), diabetes mellitus (DM), sleep apnea (SA), age, gender, weight, body mass index (BMI), and surgery type. Multivariate logistic regression analysis was performed for each procedure type. Results: There were 48 (1.5%) deaths. Independent risk factors for death included leak, weight, procedure type, and HTN. A total of 102 (3.2%) leaks were found. Independent factors for leak included age, male gender, SA, and procedure type. Conclusion: The data suggests that older, heavier male patients with multiple comorbid conditions are at increased risk for leak and mortality. Surgeons early in their learning curve should avoid these high-risk patients to reduce complications.

Baseline data from American Society for Metabolic and Bariatric Surgery-designated Bariatric Surgery Centers of Excellence using the Bariatric Outcomes Longitudinal Database

BACKGROUND The Bariatric Outcomes Longitudinal Database (BOLD) is a registry of self-reported bariatric surgery patient information from the American Society for Metabolic and Bariatric Surgery Bariatric Surgery Center of Excellence participants. The present study was undertaken to define the baseline characteristics of the patients with data entered into BOLD. METHODS The data submitted by >800 surgeons and >450 facilities using BOLD before May 20, 2009, were analyzed. RESULTS A total of 57,918 research-consented patients with surgical procedure data were included. Of the 57,918 patients, 41,243 were adults aged 26-55 years, with few patients aged < or =18 years (.14%) or > or = 66 years (5.67%). Females constituted a significant majority of the study population (45,619 [78.76%]). Of the 57,918 patients, 78.12% registered were described as Caucasian, 10.52% as African-American, 6.02% as Hispanic, .20% as Asian, and .46% as Native American. The most common bariatric surgical procedure was some form of gastric bypass (31,668 [54.68%]), followed by some form of gastric banding (22,947 [39.62%]), sleeve gastrectomy (1,328 [2.29%]), and biliopancreatic diversion (517 [.89%]). The vast majority of index procedures were completed using laparoscopic surgery techniques, except for biliopancreatic diversion, which was primarily done with an open approach. Through May 2009, 78 deaths were reported at any point after the index procedure, for a mortality rate of .13%. The 90-day mortality rate was .11%, and the 30-day mortality rate was .09%. CONCLUSION This is the first report of data from BOLD. The data have revealed important characteristics of patients undergoing bariatric surgery across the United States in centers participating in the Bariatric Surgery Center of Excellence program. Future analyses of BOLD data are likely to have a major effect on the specialty of bariatric surgery.

Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability.

OBJECTIVE The purpose of this study was to quantitate the derangements in intermediary carbohydrate metabolism and oxygen use in severely septic patients in comparison with healthy volunteers. SUMMARY BACKGROUND DATA It commonly has been assumed that the development of lactic acidosis during sepsis results from a deficit in tissue oxygen availability. Dichloroacetate (DCA), which is known to increase pyruvate oxidation but only when tissue oxygen is available, provides a means to assess the role of hypoxia in lactate production. METHODS Stable isotope tracer methodology and indirect calorimetry was used to determine the rates of intermediary carbohydrate metabolism and oxygen use in five severely septic patients with lactic acidosis and six healthy volunteers before and after administration of DCA. RESULTS Oxygen consumption and the rates of glucose and pyruvate production and oxidation were substantially greater (p < 0.05) in the septic patient compared with healthy volunteers. Administration of DCA resulted in a further increase in oxygen consumption and the percentage of glucose and pyruvate directed toward oxidation. Dichloroacetate also decreased glucose and pyruvate production, with a corresponding decrease in plasma lactate concentration. CONCLUSIONS These findings clearly indicate that the accumulation of lactate during sepsis is not the result of limitations in tissue oxygenation, but is a sequelae to the markedly increased rate of pyruvate production. Furthermore, the substantially higher rate of pyruvate oxidation in the septic patients refutes the notion of a sepsis-induced impairment in pyruvate dehydrogenase activity.

Laparoscopic intraperitoneal polytetrafluoroethylene (PTFE) prosthetic patch repair of ventral hernia. Prospective comparison to open prefascial polypropylene mesh repair.

AbstractBackground: The purpose of this study was to determine whether laparoscopic intraperitoneal polytetrafluoroethylene (PTFE) prosthetic patch (LIPP) repair of a ventral hernia is superior to open prefascial polypropylene mesh (OPPM) repair in a tertiary care university hospital in an urban environment. Methods: Data on 39 consecutive patients undergoing either LIPP repair (n= 21) or OPPM repair (n= 18) were compared. Results: Findings showed that LIPP repair is characterized by less painful recovery and shorter hospital stay, with 90% of patients treated successfully as outpatients as compared with 7% in the OPPM group. The total facility costs for the LIPP repair (