PDGFRα/PDGFRß signaling balance modulates progenitor cell differentiation into white and beige adipocytes.

The relative abundance of thermogenic beige adipocytes and lipid-storing white adipocytes in adipose tissue underlie its metabolic activity. The roles of adipocyte progenitor cells, which express PDGFRα or PDGFRß, in adipose tissue function have remained unclear. Here, by defining the developmental timing of PDGFRα and PDGFRß expression in mouse subcutaneous and visceral adipose depots, we uncover depot specificity of pre-adipocyte delineation. We demonstrate that PDGFRα expression precedes PDGFRß expression in all subcutaneous but in only a fraction of visceral adipose stromal cells. We show that high-fat diet feeding or thermoneutrality in early postnatal development can induce PDGFRß+ lineage recruitment to generate white adipocytes. In contrast, the contribution of PDGFRß+ lineage to beige adipocytes is minimal. We provide evidence that human adipose tissue also contains distinct progenitor populations differentiating into beige or white adipocytes, depending on PDGFRß expression. Based on PDGFRα or PDGFRß deletion and ectopic expression experiments, we conclude that the PDGFRα/PDGFRß signaling balance determines progenitor commitment to beige (PDGFRα) or white (PDGFRß) adipogenesis. Our study suggests that adipocyte lineage specification and metabolism can be modulated through PDGFR signaling.

Outcomes of primary versus revisional robotically assisted laparoscopic Roux-en-Y gastric bypass: a multicenter analysis of ten-year experience.

BACKGROUND: Postoperative morbidity after laparoscopic bariatric surgery is considered higher for patients undergoing revisional versus primary procedures. The objective of this retrospective cohort study was to compare outcomes between patients undergoing primary versus revisional robotically assisted laparoscopic (RAL) Roux-en-Y gastric bypass (RYGB). METHODS: Data of all patients who underwent RAL primary and revisional RYGB between 2009 and 2019 at two accredited, high-volume bariatric surgery centers-the Memorial Hermann - Texas Medical Center, Houston, TX, and the Tower Health, Reading Hospital, Reading, PA, were analyzed. Primary outcomes were early (< 30 days) and overall postoperative complications. Secondary outcomes included intraoperative complications, operative times, conversions to laparotomy, length of hospital stay, early (< 30 days) postoperative readmissions and deaths. RESULTS: Data of 1072 patients were analyzed, including 806 primary and 266 revisional RAL RYGB procedures. Longer operative times (203 versus 154 min, P < 0.001), increased number of readmissions for oral intolerance (10.5% versus 6.7%, P = 0.046) and higher rate of gastrojejunal stricture (6.4% versus 2.7%, P = 0.013) were found in the revisional group. Gastrointestinal leak rates were 0.2% for the primary versus 1.1% for the revisional group (P = 0.101). Early (< 30 days) reoperations rates were 2.2% for the primary versus 1.1% for the revisional group (P = 0.318). There were no statistically significant differences between groups in overall and severe complication rates. CONCLUSION: Patients undergoing RAL primary and revisional RYGB had comparable overall outcomes, with a non-significant higher early complication rate in the revisional group. Despite the study being underpowered to detect differences in specific complication rates, the morbidity seen in the revisional RYGB group remains markedly below literature reports of revisional laparoscopic RYGB and might suggest a benefit of robotic assistance. Further prospective studies are needed to confirm these results.

Trocar site closure with a novel anchor-based (neoClose®) system versus standard suture closure: a prospective randomized controlled trial.

BACKGROUND: Patients with obesity have a higher risk of trocar site hernia. The objective of the present study was to compare a standard suture passer versus the neoClose® device for port site fascial closure in patients with obesity undergoing laparoscopic bariatric surgery. METHODS: This is a randomized, controlled trial with two parallel arms. Thirty five patients with BMI ≥ 35 kg/m2 and undergoing laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass were randomized to each group. Port site fascial closure for trocars ≥ 10 mm was performed with the neoClose® device in the study group and the standard suture passer in the control group. Primary outcomes were time required to complete closure and intensity of postoperative pain at the fascial closure sites. Secondary outcomes were intraabdominal needle depth and incidence of trocar site hernia. RESULTS: The use of the neoClose® device resulted in shorter closure times (20.2 vs 30.0 s, p = 0.0002), less pain (0.3 vs 0.9, p = 0.002) at port closure sites, and decreased needle depth (3.3 cm vs 5.2 cm, p < 0.0001) compared to the standard suture passer. There was no trocar site hernia at the one-year follow-up in either group. CONCLUSIONS: Use of the neoClose® device resulted in faster fascial closure times, decreased intraoperative needle depth, and decreased postoperative abdominal pain at 1 week as compared to the standard suture passer. These data need to be confirmed on larger cohorts of patients with longer follow-up.

Safety of robotic assisted laparoscopic recurrent paraesophageal hernia repair: insights from a large single institution experience.

BACKGROUND: Laparoscopic repair of recurrent as opposed to primary paraesophageal hernias (PEHs) are historically associated with increased peri-operative complication rates, worsened outcomes, and increased conversion rates. The robotic platform may aid surgeons in these complex revision procedures. The aim of this study was to compare the outcomes of patients undergoing robotic assisted laparoscopic (RAL) repair of recurrent as opposed to primary PEHs. METHODS: Patients undergoing RAL primary and recurrent PEH repairs from 2009 to 2017 at a single institution were reviewed. Demographics, use of mesh, estimated blood loss, intra-operative complications, conversion rates, operative time, rates of esophageal/gastric injury, hospital length of stay, re-admission/re-operation rates, recurrence, dysphagia, gas bloat, and pre- and post-operative proton pump inhibitor (PPI) use were analyzed. Analysis was accomplished using Chi-square test/Fischer's exact test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: There were 298 patients who underwent RAL PEH repairs (247 primary, 51 recurrent). They were followed for a median (interquartile range) of 120 (44, 470) days. There were no significant differences in baseline demographics between groups. Patients in the recurrent PEH group had longer operative times, increased use of mesh, and increased length of hospital stay. They were also less likely to undergo fundoplication. There were no significant differences in estimated blood loss, incidence of intra-operative complications, re-admission rates, incidence of post-operative dysphagia and gas bloat, and incidence of post-operative PPI use. There were no conversions to open operative intervention or gastric/esophageal injury/leaks. CONCLUSIONS: Although repair of recurrent PEHs are historically associated with worse outcomes, in this series, RAL recurrent PEH repairs have similar peri-operative and post-operative outcomes as compared to primary PEH repairs. Whether this is secondary to the potential advantages afforded by the robotic platform deserves further study.

Correction to: Trocar site closure with a novel anchor-based (neoClose®) system versus standard suture closure: a prospective randomized controlled trial.

After careful review, the authors have noticed the following mistakes in the article entitled "Trocar site closure with a novel anchor based (neoClose®) system versus standard suture closure: A prospective randomized controlled trial": - Correct closure times are 19.9 seconds (SD 9.9) for the study group and 31.0 seconds (SD 20.1) for the control group (initial incorrect values were 20.2 seconds (SD 10.1) and 30 seconds (SD 19.1) respectively). The new correct P-value is <0.0001 (initial incorrect P-value was 0.0002). - Correct maximal needle depth values are 3.2 cm (SD 0.93) for the study group and 4.9 cm (SD 1.97) for the control group (initial incorrect values were 3.3 cm (SD 0.9) and 5.2 cm (SD 1.6) respectively). P-value remains unchanged at <0.0001. For these two outcomes, some values of control group patients were mistakenly included in the study group. These errors only marginally affected the mean and standard deviation values. Statistical significance of the results was not affected and the conclusions of the study remain unchanged.

Integration of etched facet, electrically pumped, C-band Fabry-Pérot lasers on a silicon photonic integrated circuit by transfer printing.

We report on the heterogeneous integration of electrically pumped InP Fabry-Pérot lasers on a SOI photonic integrated circuit by transfer printing. Transfer printing is a promising micromanipulation technique that allows the heterogeneous integration of optical and electronic components realized on their native substrate onto a target substrate with efficient use of the source material, in a way that can be scaled to parallel manipulation and that allows mixing components from different sources onto the same target. We pre-process transfer printable etched facet Fabry-Pérot lasers on their native InP substrate, transfer print them into a trench defined in an SOI photonic chip and post-process the printed lasers on the target substrate. The laser facet is successfully butt-coupled to the photonic circuit using a silicon inverse taper based spot size converter. Milliwatt optical output power coupled to the Si waveguide circuit at 100 mA is demonstrated.

Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial.

BACKGROUND & AIMS: Transoral esophagogastric fundoplication (TF) can decrease or eliminate features of gastroesophageal reflux disease (GERD) in some patients whose symptoms persist despite proton pump inhibitor (PPI) therapy. We performed a prospective, sham-controlled trial to determine if TF reduced troublesome regurgitation to a greater extent than PPIs in patients with GERD. METHODS: We screened 696 patients with troublesome regurgitation despite daily PPI use with 3 validated GERD-specific symptom scales, on and off PPIs. Those with at least troublesome regurgitation (based on the Montreal definition) on PPIs underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses. Patients with GERD and hiatal hernias ≤2 cm were randomly assigned to groups that underwent TF and then received 6 months of placebo (n = 87), or sham surgery and 6 months of once- or twice-daily omeprazole (controls, n = 42). Patients were blinded to therapy during follow-up period and reassessed at 2, 12, and 26 weeks. At 6 months, patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy. RESULTS: By intention-to-treat analysis, TF eliminated troublesome regurgitation in a larger proportion of patients (67%) than PPIs (45%) (P = .023). A larger proportion of controls had no response at 3 months (36%) than subjects that received TF (11%; P = .004). Control of esophageal pH improved after TF (mean 9.3% before and 6.3% after; P < .001), but not after sham surgery (mean 8.6% before and 8.9% after). Subjects from both groups who completed the protocol had similar reductions in GERD symptom scores. Severe complications were rare (3 subjects receiving TF and 1 receiving the sham surgery). CONCLUSIONS: TF was an effective treatment for patients with GERD symptoms, particularly in those with persistent regurgitation despite PPI therapy, based on evaluation 6 months after the procedure. Clinicaltrials.gov no: NCT01136980.

CT angiography for safe discharge of patients with possible acute coronary syndromes.

BACKGROUND: Admission rates among patients presenting to emergency departments with possible acute coronary syndromes are high, although for most of these patients, the symptoms are ultimately found not to have a cardiac cause. Coronary computed tomographic angiography (CCTA) has a very high negative predictive value for the detection of coronary disease, but its usefulness in determining whether discharge of patients from the emergency department is safe is not well established. METHODS: We randomly assigned low-to-intermediate-risk patients presenting with possible acute coronary syndromes, in a 2:1 ratio, to undergo CCTA or to receive traditional care. Patients were enrolled at five centers in the United States. Patients older than 30 years of age with a Thrombolysis in Myocardial Infarction risk score of 0 to 2 and signs or symptoms warranting admission or testing were eligible. The primary outcome was safety, assessed in the subgroup of patients with a negative CCTA examination, with safety defined as the absence of myocardial infarction and cardiac death during the first 30 days after presentation. RESULTS: We enrolled 1370 subjects: 908 in the CCTA group and 462 in the group receiving traditional care. The baseline characteristics were similar in the two groups. Of 640 patients with a negative CCTA examination, none died or had a myocardial infarction within 30 days (0%; 95% confidence interval [CI], 0 to 0.57). As compared with patients receiving traditional care, patients in the CCTA group had a higher rate of discharge from the emergency department (49.6% vs. 22.7%; difference, 26.8 percentage points; 95% CI, 21.4 to 32.2), a shorter length of stay (median, 18.0 hours vs. 24.8 hours; P<0.001), and a higher rate of detection of coronary disease (9.0% vs. 3.5%; difference, 5.6 percentage points; 95% CI, 0 to 11.2). There was one serious adverse event in each group. CONCLUSIONS: A CCTA-based strategy for low-to-intermediate-risk patients presenting with a possible acute coronary syndrome appears to allow the safe, expedited discharge from the emergency department of many patients who would otherwise be admitted. (Funded by the Commonwealth of Pennsylvania Department of Health and the American College of Radiology Imaging Network Foundation; ClinicalTrials.gov number, NCT00933400.).

Stent induced gastric wall erosion and endoscopic retrieval of nonadjustable gastric band: a new technique.

INTRODUCTION: In gastrointestinal surgery, specifically in bariatric surgery, there are many types of fixed bands used for restriction and there are a multitude reasons that might eventually be an impetus for the removal of those bands. Bands consisting of Marlex or non silastic materials can be extremely difficult to remove. Intraoperative complications removing fixed bands include the difficulty in locating the band, inability to remove all of the band, and damage to surrounding structures including gastrotomies. Removal of eroded bands endoscopically may pose less risk. Potentially, forced erosion may be an easier modality than surgery, allowing revision without having to deal with the actual band at the time of definitive revision surgery. METHODS: A retrospective case series developed from a university single institution bariatric practice setting was utilized. Endpoints for the study include success of band removal, complications, length of time the stent was present, and the type of stent. RESULTS: A total of 15 consecutive cases utilizing endoscopic stenting to actively induce fixed gastric band erosion for subsequent endoscopic removal were reviewed. There was an 87 % success rate in complete band removal with partial removal of the remaining bands that resolved the patient's symptoms. A complication rate of 27 % was recorded among the 15 patients, consisting of pain and/or nausea and vomiting. The mean time period of the placement of the stent prior to removal or attempted removal was 16.3 days. CONCLUSION: Endoscopic forced erosion of fixed gastric bands is feasible, safe, and may offer an advantage over laparoscopic removal. This technique is especially applicable for gastric obstruction from fixed bands, prior to large and definitive revision surgeries, or anticipated hostile anatomy that might preclude an abdominal operation altogether.

Robotically assisted revision of bariatric surgeries is safe and effective to achieve further weight loss.

BACKGROUND: As more bariatric operations are being performed in the USA every year, the number of revisions has increased. These operations are challenging and have a higher morbidity than the initial operation. We have reviewed our series of robotically assisted revisions. METHODS: At the University of Texas Medical School at Houston, we reviewed robotic revision cases from 2004 through 2011 and found 99 bariatric revisions using robotic assistance. Selected endpoints included body mass index (BMI) at follow-up, percent excess weight loss (%EWL), complications, intubation time, operative time, and length of hospital stay. RESULTS: The average BMI at the time of revision was 44.8 kg/m(2) and fell to 29 kg/m(2) after 3 years. BMI was significantly lower at all time intervals (3, 12, 24, and 36 months) compared to initial BMI (p < 0.001). The %EWL was also significant at 1, 3, 12, 24, and 36 months post-revision (p < 0.001). There was a 24 % (13/55) 90-day readmission rate. The overall complication rate was 17 %, with each individual complication rate between 2 and 4 %. There were no deaths. The average operative time was 204 min, and the average length of hospital stay was 2.3 days. CONCLUSIONS: Revising previous bariatric operations to gastric bypass is difficult and time consuming. Although robotically assisted revision can be done safely and can result in effective further weight loss, the high postoperative complication rate is an issue that warrants further attention.

Technical feasibility of robot-assisted ventral hernia repair.

BACKGROUND: The da Vinci robotic laparoscopic incisional hernia repair with intracorporeal closure of the fascial defect and circumferential suturing of the mesh may offer an alternative to current fascial closure and transabdominal sutures and tackers. METHODS: From 2009 to 2011, a retrospective review of 13 patients with a mean age of 51 years, median body mass index (BMI) of 31.53 kg/m(2), and small and medium-sized ventral hernias (mean fascial defect 37.39 cm(2)) were treated with the da Vinci robot system using intracorporeal primary closure of the fascial defect with a running O-absorbable suture followed by underlay mesh fixation using a continuous running, circumferential, nonabsorbable suture. This study aimed to assess the technical feasibility of the procedure. In addition, the operating time and specific morbidity of postoperative pain, and long-term recurrence were recorded. RESULTS: The mean operating time was 131 min. There were no conversions to open or standard laparoscopic techniques. There were no postoperative deaths. The overall morbidity rate was 13%. One patient remained in hospital for pain control, and another experienced urinary retention that required a Foley catheter. The mean hospital stay was 2.4 days. During a median follow-up period of 23 months, one of the patients experienced a recurrent hernia. None experienced chronic suture site pain or discomfort. CONCLUSIONS: This is a retrospective series review of robot-assisted ventral hernia repair using intracorporeal primary closure followed by continuous running, circumferential fixation. The findings show that this technique is feasible and may not be associated with chronic postoperative pain. Further evaluation is needed, and long-term data are lacking to assess the benefit to the patient, but this series can be the basis for future studies.

Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue.

Hyperplastic expansion of white adipose tissue (WAT) relies in part on the proliferation of adipocyte precursor cells residing in the stromal vascular cell fraction (SVF) of WAT. This study reveals a circadian clock- and feeding-induced diurnal pattern of cell proliferation in the SVF of visceral and subcutaneous WAT in vivo, with higher proliferation of visceral adipocyte progenitor cells subsequent to feeding in lean mice. Fasting or loss of rhythmic feeding eliminates this diurnal proliferation, while high fat feeding or genetic disruption of the molecular circadian clock modifies the temporal expression of proliferation genes and impinges on diurnal SVF proliferation in eWAT. Surprisingly, high fat diet reversal, sufficient to reverse elevated SVF proliferation in eWAT, was insufficient in restoring diurnal patterns of SVF proliferation, suggesting that high fat diet induces a sustained disruption of the adipose circadian clock. In conclusion, the circadian clock and feeding simultaneously impart dynamic, regulatory control of adipocyte progenitor proliferation, which may be a critical determinant of adipose tissue expansion and health over time.

Thromboelastography-Based Profiling of Coagulation Status in Patients Undergoing Bariatric Surgery: Analysis of 422 Patients.

INTRODUCTION/PURPOSE: Some clinical indicators suggest hypercoagulability/hyperaggregability in patients with morbid obesity. Thromboelastography (TEG®) has been used to profile coagulation status in surgical patients. We aimed to assess coagulation profiles in patients with morbid obesity undergoing bariatric surgery by correlating demographic and patient characteristics to pre-operative TEG® values. MATERIALS AND METHODS: Pre-operative TEG® values from 422 patients undergoing bariatric surgery were evaluated. TEG® results were analyzed by gender, use of medications known to alter the coagulation profile, and body mass index (BMI). RESULTS: Patients have a mean of 45.03 ± 11.8 years, female (76.3%), and with a mean BMI of 42 kg/m 1. The overall coagulation profile of female patients was significantly different from males, even in the sub-cohort without use of medications known to alter coagulation. The majority of patients (94%) with a G value > 15 dynes/cm 1 (clot strength) were female. In females, there was no association between BMI and TEG® values; however, in men, there was a statistically significant difference in TEG® values for those with BMI < 40 kg/m 1 compared to those with BMI > 50 kg/m2. CONCLUSIONS: TEG®-based analysis of coagulation profiles offers unique insights. Compared to laboratory normal values (R time, angle, maximal amplitude, and G values), patients with morbid obesity may have a tendency for hypercoagulability/hyperaggregability, with mean values at the higher limit. A significant hypercoagulable difference in TEG® values was identified in female as compared to male patients. Male patients with a BMI greater than 50 kg/m2 were also found to be increasingly hypercoagulable.

Endoscopic management of eroded prosthesis in vertical banded gastroplasty patients.

INTRODUCTION: One of the major complications of applying a prosthetic device to facilitate gastric partitioning has been intraluminal erosion of the prosthesis. Removing an eroded gastric band is fraught with difficulty secondary to the extensive inflammatory response around the proximal stomach and left lobe of the liver. As a result, bariatric clinicians have attempted to apply endoscopic technology to facilitate removal of eroded gastric prostheses. Our study reports on our experience of applying endoscopic scissor transection to remove eroded gastric prostheses in a large tertiary-care medical center. METHODS: A retrospective chart review was conducted to identify all adult (>18 years old) patients managed endoscopically for removal of eroded prosthesis post bariatric surgery at the Baylor College of Medicine Comprehensive Bariatric Surgery Center and the University of Texas-Houston Bariatric Surgery Program. RESULTS: Nine patients, mean body mass index (BMI) 39.5 +/- 7.3 kg/m(2), were managed endoscopically to remove eroded gastric prosthesis post vertical banded gastroplasty. All patients (9/9) reported symptoms consistent with a proximal gastric outlet obstruction (dysphagia, nausea, vomiting). Inadequate weight loss was reported by 67% (6/9) of patients. The mean time for endoscopic band removal was 28.0 +/- 8.8 min. All eroded bands were evident at the end of the gastric pouch and were visualized with either a normal or retroflexed endoscopic view. All nine patients were discharged the same day of their procedure. Mean follow-up of the patients was 9.7 weeks (1-30 weeks). Three patients underwent revisional bariatric surgery following the band removal. CONCLUSION: Our study demonstrates that endoscopic scissor transaction is a safe and effective modality in removing eroded gastric prostheses after vertical banded gastroplasty and avoids the pitfalls associated with removing the eroded bands surgically. It also allows the patient and surgeon to make an insightful decision regarding a revisional bariatric surgical procedure, without being contingent on addressing the eroded gastric band.

Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease.

White and beige adipocytes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are maintained by proliferation and differentiation of adipose progenitor cells (APCs). Here we use mice with tissue-specific telomerase reverse transcriptase (TERT) gene knockout (KO), which undergo premature telomere shortening and proliferative senescence in APCs, to investigate the effect of over-nutrition on APC exhaustion and metabolic dysfunction. We find that TERT KO in the Pdgfra+ cell lineage results in adipocyte hypertrophy, inflammation and fibrosis in SAT, while TERT KO in the Pdgfrb+ lineage leads to adipocyte hypertrophy in both SAT and VAT. Systemic insulin resistance is observed in both KO models and is aggravated by a high-fat diet. Analysis of human biopsies demonstrates that telomere shortening in SAT is associated with metabolic disease progression after bariatric surgery. Our data indicate that over-nutrition can promote APC senescence and provide a mechanistic link between ageing, obesity and diabetes.

Comparison of those who succeed in losing significant excessive weight after bariatric surgery and those who fail.

BACKGROUND: Gastric bypass and adjustable gastric banding currently are the most commonly performed weight loss surgeries. The results are encouraging for most patients, but some patients have a better experience than others. This report aims to define differences between those who succeeded and those that failed to lose significant excessive weight after bariatric surgery. METHODS: The authors retrospectively reviewed their database over the past 4 years. They studied 484 bariatric patients who had 1 year of follow-up evaluation. Success was defined as more than 50% excess weight loss (EWL) and failure as less than 30% EWL. Student's t-tests were performed between the groups of bypass patients, band patients, men, women, whites, and minorities. RESULTS: An overall success rate of 58% and a failure rate of 15% were observed. The successful group was significantly younger. The starting body mass index (BMI) was significantly lower for the successful band patients. The starting excess weight was significantly less in both the successful band and bypass groups, as was the starting weight. The successful whites were significantly younger, and the starting BMI was significantly lower in the successful minority group. The unsuccessful bypass patients and whites were significantly taller than the successful group. Gender was not a significant variable in success or failure regardless of procedure. CONCLUSION: Without consideration for the procedure performed, the patients who successfully lost weight were younger. The unsuccessful band patients had a higher starting BMI, whereas the successful band and bypass patients had lower average starting and excess weights. The successful bypass patients were significantly shorter. Among whites, the successful patients were significantly younger and shorter. The successful minorities had a lower starting BMI. These variables give further insight into the complexity of successful excess weight loss.

Failure of adjustable gastric banding: starting BMI of 46 kg/m2 is a fulcrum of success and failure.

BACKGROUND: To determine the body mass index (BMI) located at the fulcrum of success and failure in a prospective study conducted at the University of Texas Health Science Center at Houston. On average, our patients whose percentage of excess weight loss (%EWL) was >50% at 1 year had a significantly lower BMI than those with <30% EWL. METHODS: We prospectively collected the weight loss data for 430 patients who had had an adjustable gastric band placed. We stratified the %EWL within 1 year for patients with a BMI of 30-59 kg/m2. A line was generated for the %EWL over time for BMI groups of 30-39, 40-49, and 50-59 kg/m(2) and compared with the average %EWL over time. The y-intercepts of the resulting four lines were graphed against the average BMI for each group. RESULTS: The generated y-intercept line had an R2 of .9237. Using the equation of this line and the known y-intercept for the average, we solved for x, resulting in a BMI of 46 kg/m2. Patients with a BMI <46 kg/m2 had a 50% EWL at 1 year, and those with a BMI >46 kg/m2 had only a 33% EWL at 1 year. The %EWL between the groups was significantly different at all measured intervals (P <.0001). CONCLUSION: A BMI of 46 kg/m2 identifies those at high risk of failure to lose a significant percentage of excess weight after adjustable gastric banding and who require closer follow-up. Furthermore, patients who have a BMI >46 kg/m2 should be advised that their weight loss might be suboptimal at 1 year.

Histidine inhibits the degradation of cells suspended in Ringer's lactate.

BACKGROUND: We previously demonstrated that the degradation of a suspension of Jurkat cells in Ringer's lactate (RL) was inhibited by the addition of a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid/Tris buffer. Given the ability of histidine to buffer protons in the physiologic range (pKa = 6.0), we hypothesized that this amino acid would have the same effect. METHODS: RL was made in our laboratory using sodium l-lactate. Jurkat cells were suspended in RL alone or RL with various concentrations of histidine or other test reagents at 37 degrees C for 4 hours or 24 hours in an atmosphere of 95% air and 5% CO2. Using flow cytometry, we measured cell shrinkage, phosphatidylserine translocation, propidium iodide uptake, and intracellular oxygen free radical production. RESULTS: Cell shrinkage was induced by suspension in RL after 4 hours incubation. At 4 hours, cell shrinkage was inhibited by all concentrations of histidine tested, 7.8 mumol/L to 10 mmol/L. There was no statistical difference between cells suspended in medium and cells suspended in 1 mmol/L or 10 mmol/L histidine. After 24 hours incubation, 100% of the cells in RL had undergone cell shrinkage whereas in 10 mmol/L histidine only a mean of 20% of the cells had undergone cell shrinkage. The inhibitory effect of 1 mmol/L histidine at pH 7.4 was compared with that at pH 6.8. After 4 hours incubation, there was no difference. After 24 hours incubation, the inhibitory effect at pH 7.4 was significantly greater that that at pH 6.8. Histidine at 1 mmol/L to 10 mmol/L significantly reduced the percentage of cells that underwent phosphatidylserine translocation and propidium iodide uptake. The effect of the dipeptide buffer, glycylglycine, and the two other positively charged amino acids, arginine and lysine, after 4 hours incubation was compared with histidine at 1 mmol/L. At 1 mmol/L, histidine was superior to arginine and lysine and indistinguishable from glycylglycine. Intracellular free radical production was measured at 0.5 mmol/L, 1.0 mmol/L, and 10 mmol/L histidine concentrations. There was significant inhibition only at 10 mmol/L. CONCLUSIONS: Characteristics of apoptotic cell death that occur in cells suspended in RL are inhibited by the addition of histidine, arginine, and lysine as well as the dipeptide glycylglycine, which, with a pKa of 8.25, also buffers in the physiologic range. Histidine is superior to lysine and arginine at 1 mmol/L. The salutary effect of histidine at 0.5 mmol/L and 1 mmol/L is caused by a mechanism other than the inhibition of oxygen free radicals. Moreover, the buffering of protons may play a role at 24 hours but made no difference at 4 hours.

Genital tract interleukin-8 but not interleukin-1beta or interleukin-6 concentration is associated with bacterial vaginosis and its clearance in HIV-infected and HIV-uninfected women.

Genital tract infections and cytokine perturbations are associated with increased HIV acquisition and transmission. We measured the relationship between bacterial vaginosis (BV) and concentrations of Interleukin-8 (IL-8), Interleukin-1beta (IL-1beta), and Interleukin-6 (IL-6) in cervicovaginal lavage (CVL) specimens collected longitudinally from 16 HIV-infected and 8 HIV-uninfected high-risk women. CVL samples were analyzed when women presented with BV, and at their next visit, after successful treatment, when BV was cleared. A subset of participants had cytokine levels evaluated at three consecutive clinic visits: before developing BV, at the time of BV diagnosis, and after clearing BV. Significantly higher IL-8, but not IL-1beta or IL-6 levels were present when women had active BV compared to when BV was absent. Trends in cytokine levels were similar for HIV-infected and HIV-uninfected women. BV in these women was associated with significantly higher concentrations of genital tract IL-8 which decreased 2.4 fold when BV was cleared.

Non-glycanated Decorin Is a Drug Target on Human Adipose Stromal Cells.

Adipose stromal cells (ASCs) have been identified as a mesenchymal cell population recruited from white adipose tissue (WAT) by tumors and supporting cancer progression. We have previously reported the existence of a non-glycanated decorin isoform (ngDCN) marking mouse ASCs. We identified a peptide CSWKYWFGEC that binds to ngDCN and hence can serve as a vehicle for ASC-directed therapy delivery. We used hunter-killer peptides composed of CSWKYWFGEC and a pro-apoptotic moiety to deplete ASCs and suppress growth of mouse tumors. Here, we report the discovery of the human non-glycanated decorin isoform. We show that CSWKYWFGEC can be used as a probe to identify ASCs in human WAT and tumors. We demonstrate that human ngDCN is expressed on ASC surface. Finally, we validate ngDCN as a molecular target for pharmacological depletion of human ASCs with hunter-killer peptides. We propose that ngDCN-targeting agents could be developed for obesity and cancer treatment.