TAVAC: comprehensive review of currently available hemostatic products as adjunct to surgical hemostasis.

BACKGROUND: The use of hemostatic agents by general surgeons during abdominal operations is commonplace as an adjunctive measure to minimize risks of postoperative bleeding and its downstream complications. Proper selection of products can be hampered by marginal understanding of their pharmacokinetics and pharmacodynamics. While a variety of hemostatic agents are currently available on the market, the choice of those products is often confusing for surgeons. This paper aims to summarize and compare the available hemostatic products for each clinical indication and to ultimately better guide surgeons in the selection and proper use of hemostatic agents in daily clinical practice. METHODS: We utilized PubMed electronic database and published product information from the respective pharmaceutical companies to collect information on the characteristics of the hemostatic products. RESULTS: All commercially available hemostatic agents in the US are described with a description of their mechanism of action, indications, contraindications, circumstances in which they are best utilized, and expected results. CONCLUSION: Hemostatic products come with many different types and specifications. They are valuable tools to serve as an adjunct to surgical hemostasis. Proper education and knowledge of their characteristics are important for the selection of the right agent and optimal utilization.

TAVAC: choledochoscopy disposable scopes, and the single-stage vs. two-stage approach to choledocholithiasis.

BACKGROUND: Previous studies have been published evaluating the benefits and drawbacks of clearing the common bile duct of stones using a single-stage approach (LCBDE + LC) versus a two-stage approach (ERCP followed by LC). These studies have demonstrated that a single-stage approach offers similar outcomes and morbidities as a two-stage approach, with the added benefit of a lower cost and shorter length of stays. However, it is significant we understand why LCBDE is not commonly performed currently and also the lapse in surgical trainee exposure and competence in LCBDE. This paper aims to address the lapse in surgical trainee exposure to LCBDE, evaluate the scopes currently available to perform LCBDE, and review current data evaluating the risks and benefits of single-stage versus two-stage approaches to. METHODS: We utilized PubMed to analyze all publications related to the various disposable scopes utilized to perform choledochoscopy. We also discuss the need for disposable scopes and how this new market niche is transforming the choledochoscopy space. RESULTS: We analyzed the data related to single-stage and two-stage approach to choledocholithiasis. We noted an overall shorter length of stay and also decreased costs in favor of a single-stage approach. CONCLUSION: A single-stage LCBDE is the most cost-effective treatment option for choledocholithiasis in patients with choledocholithiasis undergoing a cholecystectomy. In addition, single-stage approach is associated with shorter length of stay. Knowledge of the available choledochoscopes and tools available to surgeons to perform choledochoscopy is significant. The evidence does support the use of disposable choledochoscope from a cost and cross-contamination perspective. Additionally, efforts should be made to incorporate LCBDE into the teaching paradigm of surgical training programs.

Effect of Smoking History on 30-Day Morbidity Following Bariatric Surgery.

INTRODUCTION: Smoking and postoperative complications are well documented across surgical specialties. Preoperative smoking cessation is frequently recommended by surgeons. In this study, we assessed to what degree documented smoking history increased a patient's risk of postoperative complications. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database for the years 2015-2018 was used. Patients were included if they underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (LRYGB). Patients with a documented smoking history were assigned to the "SH" cohort and patients without smoking history were assigned to the "NSH" cohort. Patients without documentation regarding smoking history, missing variables, younger than 18, with prior surgery, or lost to follow-up were excluded. 30-day morbidity and mortality data were assessed. Multiple logistic regression analysis was made based on all available patient characteristics and perioperative factors, continuous variables were analyzed using Student's t-test and categorical variables were compared using the chi-square test. RESULTS: After evaluation of 760,076 patients on the MBSAQIP database, 650,930 patients underwent non-revisional bariatric surgery, including 466,270 SG and 184,660 LRYGB. Of the total patients included in the study, 44,606 patients were assigned to the SH cohort and 479,601 were assigned to the NSH cohort. 4628 of patients did not have documented smoking status. Within 30 days SH patients had higher rates of readmission (4.2% vs 3.7%, P < .0001), reoperation (1.3% vs 1.1%, P < .0001), unplanned intubation (.2% vs .1%, P = .0212), and unplanned ICU admission (.7% vs .0.6%, P = .0022). CONCLUSION: SH patients undergoing bariatric surgery were at significantly increased risk of readmission and reoperation within 30 days of procedure. In addition, SH patients were more likely to have unplanned intubation and unplanned ICU admission. Given the higher rates of complications in smoking patients, this study would suggest that preoperative smoking cessation in patients prior to primary bariatric surgery might be beneficial. Further study is warranted to compare short-term cessation vs long-term cessation preoperatively, which was not assessed in our study.

A SAGES technology and value assessment and pediatric committee evaluation of mini-laparoscopic instrumentation.

BACKGROUND: The TAVAC and Pediatric Committees of SAGES evaluated the current use of mini-laparoscopic instrumentation to better understand the role this category of devices plays in the delivery of minimally invasive surgery today. METHODS: The role of mini-laparoscopic instrumentation, defined as minimally invasive instruments of between 1 and 4 mm in diameter, was assessed by an exhaustive review of the peer reviewed literature on the subject between 1990 and 2021. The instruments, their use, and their perceived value were tabulated and described. RESULTS: Several reported studies propose a value to using mini-laparoscopic instrumentation over the use of larger instruments or as minimally invasive additions to commonly performed procedures. Additionally, specifically developed smaller-diameter instruments appear to be beneficial additions to our minimally invasive toolbox. CONCLUSIONS: The development of small instrumentation for the effective performance of minimally invasive surgery, while perhaps best suited to pediatric populations, proves useful as adjuncts to a wide variety of adult surgical procedures. Mini-laparoscopic instrumentation thus proves valuable in selected cases.

Weight loss one year after laparoscopic roux-en-Y gastric bypass is not dependent on the type of gastrojejunal anastomosis.

BACKGROUND: Laparoscopic roux-en-Y gastric bypass (LRYGB) is the gold standard weight-loss procedure. There are different techniques to perform the gastrojejunal (GJ) anastomosis, but there is no consensus as to which one is superior for weight loss. Our goal in this study was to assess one-year weight loss after LRYGB comparing the three different techniques at our tertiary care center. METHODS: The American college of surgeons (ACS) Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP®) data for Montefiore Medical Center for years 2014-2017 were analyzed. Three surgeons were included in this study; each type of anastomosis was performed by a single surgeon. Patients were included if they underwent primary LRYGB. Patients were designated to one of three different groups depending of the type of gastrojejunal anastomosis performed: hand sewn, circular stapled, or linear stapled. One-year weight loss was assessed as primary endpoint of the study. A descriptive analysis of perioperative variables for each group was included as well. RESULTS: A total of 1011 patients underwent primary LRYGB. 429 (42.1%) were performed with circular-stapled GJ anastomosis, 433 (42.5%) with a hand-sewn GJ anastomosis, and 149 (14.6%) linear-stapled GJ anastomosis. The median BMI was 46.08  ±  6.43, with no difference between groups (p = .405). Procedure time was 106.70  ±  28.23 min for the circular group, 108.27  ±  28.59 min for the hand-sewn group, and 115.78  ±  36.11 min for the linear group (p > 0.005). There were no significant differences in complications except for the need of postoperative transfusions (p < 0.002). There was no statistically significant difference in %EWL one year after surgery: %EWL was 58.81  ±  16.54 kg for hand sewn, 58.86  ±  14.84 kg for circular, and 59.20  ±  17.58Kg for linear. (p = .595). CONCLUSION: There is no difference in weight loss one year after LRYGB based on the type of gastrojejunal anastomosis performed.

SubCutaneous OnLay endoscopic Approach (SCOLA) mesh repair for small midline ventral hernias with diastasis recti: An initial US experience.

BACKGROUND: Patients presenting for evaluation of umbilical and epigastric hernias are often found to have diastasis recti (DR). As isolated hernia repair in these patients may be associated with higher rates of recurrence, prior international publications have described a prefascial mesh repair in combination with anterior plication of DR. We present our initial United States (US) experience with a SubCutaneous OnLay endoscopic Approach (SCOLA) to address these concurrent pathologies in a single hybrid procedure. METHODS: Between July 2018 and December 2019, a prospective cohort of 16 patients underwent the SCOLA procedure. Subcutaneous dissection was carried out from the suprapubic region superiorly to the xiphoid process and laterally to the linea semilunaris. Hernia contents were reduced and defects were incorporated into anterior DR plication, which was performed with running barbed suture. Onlay mesh was placed to cover the entire dissected space, and subcutaneous drains were placed. Three separate attendings performed cases with one supervising attending for standard technique. RESULTS: Of 16 patients, 14 (87.5%) were female. The mean age was 45.7 (11.9) years; mean BMI was 29.0 (3.6) kg/m2. The mean hernia defect size was 1.9 (0.7) cm. Mean operative time was 146 (46.3) minutes; two (15%) cases were performed robotically. The mean follow-up time was approximately two months (63 days). Three (18.8%) patients developed seroma, one (6.3%) patient developed an infected seroma, and two (12.5%) patients developed hernia recurrence. CONCLUSIONS: SCOLA technique is shown to be a safe and effective approach for patients presenting with small midline ventral hernias and concomitant DR. Our preliminary US data demonstrates higher rates of post-operative complication in patients with higher BMI, which suggests that patient selection and pre-operative counseling is essential to achieve better technical outcomes in our patient population.

Transversus abdominis plane block with liposomal bupivacaine and its effect on opiate use after weight loss surgery: a randomized controlled trial.

BACKGROUND: Liposomal bupivacaine (LB), as an extended-release local anesthetic, may provide lasting pain control and therefore decrease the need for narcotics in the immediate postoperative period. OBJECTIVES: The aim of this study was to evaluate whether transversus abdominis plane (TAP) block with LB decreased the use of postoperative narcotics compared with regular bupivacaine (RB) and no TAP block in patients undergoing weight loss procedures. SETTING: A large, metropolitan, university-affiliated, tertiary hospital. METHODS: Patients undergoing laparoscopic Roux-en-Y gastric bypass, sleeve gastrectomy, or sleeve-to-bypass conversion over 1 year were randomized to receive TAP block using LB, TAP block with RB, or no block in a double-blind, randomized controlled trial. The outcomes measured were postoperative use of opiates, pain score, length of stay, time to ambulation, and nausea. Data were analyzed using χ2 test and analysis of variance F test. RESULTS: Two hundred nineteen patients were included in the study. Fentanyl patient-controlled analgesia usage was not significantly different between the groups (LB 351.4 versus RB 360.7 versus no TAP block 353.9, P = .97) at 48 hours post operation. The pain scores (scale 1-10) were similar among the groups with the mean for the LB group at 4.3, and RB and no TAP block groups both at 4.7 (P = .35). The type of block or lack of block did not significantly impact the length of stay, time to ambulation, or presence of nausea. CONCLUSION: The LB TAP block did not significantly reduce the total opiate pain medication consumption nor did it reduce pain scores among bariatric surgery patients.

Bariatric surgery in the super-super morbidly obese: outcome analysis of patients with BMI >70 using the ACS-NSQIP database.

BACKGROUND: Bariatric surgery offers patients short- and long-term benefits to their health and quality of life. Currently, we see more patients with superior body mass index (BMI) looking for these benefits. Evidence-based medicine is integral in the evaluation of risks versus benefit; however, data are lacking in this high-risk population. OBJECTIVES: To assess the morbidity and mortality of patients with BMI ≥70 undergoing bariatric surgery. SETTING: University Hospital, Bronx, New York, United States using national database. METHODS: Using the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) database for years 2005 to 2016, we identified patients who underwent primary laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Patients with BMI ≥70 were assigned to the BMI >70 (BMI70+) cohort and less obese patients were assigned to the BMI <70 (U70) cohort. Length of stay and 30-day morbidity and mortality were compared. RESULTS: A total of 163,413 patients underwent non-revisional bariatric surgery. Of those, 2322 had a BMI ≥70. BMI70+ was associated with increased mortality (.4% versus .1%, P = .0001), deep vein thrombosis (.6% versus .3%, P = .007), pulmonary (1.9% versus .5%, P = .0001), renal (.9% versus .2%, P = .0001), and infectious complications (1.1% versus .4%, P = .0001). BMI70+ patients had longer mean length of stay (2.6 versus 2.1 d, P = .0001) and operative time (126.1 versus 114.5 min, P = .0001). There was no statistically significant difference in the number of myocardial infarctions (.1% versus .1%, P = .319), pulmonary embolisms (.3% versus .2%, P = .596), and transfusion requirements (.1% versus .1%, P = .105) between groups. CONCLUSIONS: Evaluation of risk and benefit is performed on a case-by-case basis, but evidence-based medicine is critical in empowering surgeons and patients to make informed decisions. The overall rate of morbidity and mortality for BMI70+ patients undergoing bariatric surgery was increased over U70 patients but was still relatively low. Our study will allow surgeons to incorporate objective data into their assessment of risk for super-obese patients pursuing bariatric surgery.

Bariatric surgery in the elderly: outcomes analysis of patients over 70 using the ACS-NSQIP database.

BACKGROUND: Bariatric surgery offers patients with morbid obesity and related diseases short- and long-term benefits to their health and quality of life. Evidence-based medicine is integral in the evaluation of risk versus benefit; however, data are lacking for several high-risk patient populations, including the elderly. OBJECTIVES: This study assessed morbidity and mortality data for patients age ≥70 undergoing laparoscopic sleeve gastrectomy (SG) or laparoscopic Roux-en-Y gastric bypass (RYGB). SETTING: University Hospital, Bronx, New York, United States using national database. METHODS: We used the American College of Surgeons-National Surgical Quality Improvement Project database for years 2005-2016 and identified patients who underwent primary SG or RYGB. Patients age ≥70 were assigned to the over age 70 (AGE70+) cohort and younger patients were assigned to the under age 70 (U70) cohort. Postoperative length of stay and 30-day morbidity and mortality were assessed. RESULTS: A total of 1498 patients age ≥70 underwent nonrevisional bariatric surgery, including 751 (50.1%) SG and 747 (49.9%) RYGB. AGE70+ was associated with increased mortality and increased rates of cardiac, pulmonary, renal, and cerebrovascular morbidity. AGE70+ patients had longer mean length of stay, and were more likely to require transfusion and return to operative room. When stratified by procedure, rates of organ-space surgical site infection, acute renal failure, urinary tract infection, myocardial infarction, deep vein thrombosis/thrombophlebitis, and septic shock were significantly increased in AGE70+ patients undergoing RYGB but not SG. Impaired functional status was associated with increased rates of morbidity and mortality for AGE70+ patients and for U70 patients, although the small number of patients within each category limited statistical analysis. CONCLUSIONS: Evaluation of risk versus benefit is performed on a case-by-case basis, but evidence-based medicine is critical in empowering surgeons and patients to make informed decisions. The overall rate of morbidity and mortality for AGE70+ patients undergoing bariatric surgery was increased relative to U70 patients. Rates of several adverse events, including acute renal failure and myocardial infarction, were increased in AGE70+ patients undergoing RYGB but not SG, suggesting that SG may be the preferred procedure for elderly patients with organ-specific risk factors. The increased rates of morbidity and mortality observed for patients with impaired functional status supports consideration of functional status when evaluating preoperative risk.

Bariatric surgery in patients with left ventricular assist devices: a safe and effective method of weight loss as a gateway to heart transplantation.

BACKGROUND: Severe cardiac disease often warrants intervention to improve cardiac function, such as mechanical support via a left ventricular assist device (LVAD). While this is an effective way of improving myocardial activity, it works synergistically with weight loss. SETTING: Academic hospital. OBJECTIVE: The aim of this study was to evaluate bariatric surgery as an alternative means of weight loss to improve cardiac status. METHODS: Six patients with LVADs underwent sleeve gastrectomies (SG) over a 5-year study period (2014-2018). Patient characteristics, cardiac history, operative outcomes, and follow-up was evaluated by univariate analyses. RESULTS: Median age at operation was 49.8 years (range, 24-58 yr) with average weight at surgery of 126.6 kg. Average body mass index at time of SG was 41.4 kg/m2. Median hospital length of stay was 8.5 days (range, 4-13 d), with postoperative length of stay of 5.5 days (3-7 d). Total follow-up was 29 months (range, 7-51 mo). Postoperative readmission occurred in 2 patients (33%) without significant adverse outcomes. Four patients (67%) were listed for transplant, 3 within 1 year of LSG. Three patients (50%) underwent orthotopic heart transplant. All patients experienced improved cardiac co-morbidities after SG. CONCLUSION: We demonstrate that weight loss surgery as a bridge to transplantation for patients with implanted LVADs can be performed in young and middle-aged adults. Although it is limited by sample size, the reported results add to the existing literature highlighting the potential success of bariatric surgery in high-risk patient populations to achieve weight loss goals, impact cardiac co-morbidities, and improve overall quality of life.

Unplanned postoperative reintubation following general and vascular surgical procedures: Outcomes and risk factors.

BACKGROUND: Unplanned postoperative reintubation (UPR) is a marker for severe adverse outcomes following general and vascular surgery. STUDY DESIGN: A retrospective analysis of 8809 adult patients, aged 18 years and older, who underwent major general and vascular surgery at a large single-center urban hospital was conducted from January 2013 to September 2016. Patients were grouped into those who experienced UPR and those who did not. Univariate and multivariate regression analyses were used to identify predictors of UPR, and association of UPR with adverse postoperative outcomes. All regression models had Hosmer-Lemeshow P > 0.05, and C-statistic >0.75, indicating excellent goodness-of-fit and discrimination. RESULTS: Of the 8809 patients included, 138 (1.6%) experienced UPR. There was no statistical difference in incidence of UPR between general and vascular surgery patients (p = 0.53). Independent predictors of UPR advanced age (OR 5.1, 95%CI 3.5-7.5, p < 0.01), higher ASA status (OR 7.9, 95%CI 5.6-11.1, p < 0.01), CHF (OR 7.0, 95%CI 3.6-13.9, p = 0.02), acute renal failure or dialysis (OR 3.1, 95%CI 1.8-5.7, p = 0.01), weight loss (OR 5.2, 95%CI 2.8-9.6, p = 0.01), systemic sepsis (OR 4.8, 95%CI 3.4-6.9, p < 0.01), elevated preoperative creatinine (OR 4.2, 95%CI 3.0-5.9, p = 0.01), hypoalbuminemia (OR 5.3, 95% CI 3.8-7.5, p = 0.01), and anemia (OR 4.0, 95%CI 2.8-5.9, p < 0.01). Following surgery, UPR was associated with increased mortality (OR 3.8, 95%CI 2.7-5.2, p < 0.01), pulmonary complications (OR 1.8, 95%CI 1.7-2.0, p < 0.01), renal complications (OR 2.6, 95%CI 1.7-3.5, p < 0.01), cardiac complications (OR 4.6, 95%CI 2.0-6.7, p < 0.01), postoperative RBC transfusion (OR 5.7, 95%CI 3.8-8.6,p < 0.01), and prolonged hospitalization (OR 1.8, 95%CI 1.5-2.4, p < 0.01). CONCLUSION: UPR is significantly associated with postoperative morbidity and mortality. Perioperative management aimed at decreasing incidences of UPR after noncardiac surgery should target preoperative anemia in addition to previously identified predictors.

Risk factors contributing to cardiac events following general and vascular surgery.

BACKGROUND: Cardiac events (CE) following surgery have been associated with morbidity and mortality. Defining risk factors that contribute to CE is essential to improve surgical outcomes. STUDY DESIGN: This was a retrospective study at a large urban teaching hospital for surgery performed from 2013 to 2015. Adult patients (≥18 years) that underwent general and vascular surgery were analyzed. Patients were grouped into those who experienced postoperative CE and those who did not. Univariate and multivariate regression analyses were used to identify predictors of postoperative CE, and association of CE with adverse postoperative outcomes. Separate subgroup analyses were also conducted for general and vascular surgery patients to assess predictors of CE. RESULTS: Out of 8441 patients, 157 (1.9%) experienced CE after major general and vascular surgery. Underlying predictors for CE included age >65 years(OR 4.9, 95%CI 3.4-6.9,p < 0.01), ASA >3(OR 12.0, 95%CI 8.5-16.9,p < 0.01), emergency surgery(OR 3.7, 95%CI 2.7-5.1,p = 0.01), CHF(OR 11.2, 95%CI 6.4-16.7,p = 0.02), COPD(OR 3.9, 95%CI 2.4-6.4,p = 0.04), acute renal failure or dialysis(OR 8.0, 95%CI 5.2-12.1,p = 0.04), weight loss(OR 3.3, 95%CI 1.7-6.7,p < 0.01), preoperative creatinine >1.2 mg/dL(OR 5.1, 95%CI 3.7-7.1,p = 0.01), hematocrit <34%(OR 4.0, 95%CI 2.8-5.7,p < 0.01), and operative time >240 min(OR 2.0, 95%CI 1.3-3.3,p = 0.02). Following surgery, CE was associated with increased mortality(OR 3.5, 95%CI 1.2-6.5,p < 0.01), pulmonary complications(OR 5.0, 95%CI 3.1-8.9,p < 0.01), renal complications(OR 2.3, 95%CI 1.9-4.5,p < 0.01), neurologic complications(OR 2.5, 95%CI 1.4-5.2,p < 0.01), systemic sepsis(OR 2.2, 95%CI 1.7-4.0,p < 0.01), postoperative RBC transfusion(OR 4.4, 95%CI 2.7-6.5,p < 0.01), unplanned return to operating room(OR 4.0, 95%CI 2.3-6.9,p < 0.01), and prolonged hospitalization (OR 5.5, 95%CI 3.1-8.8,p = 0.03). There was no statistical difference in incidence of CE between general and vascular surgery patients (p = 0.44); however, predictors of CE differed between the two surgical groups. CONCLUSION: Postoperative CE are associated with significant morbidity and mortality. Identified predictors of CE should allow for adequate risk stratification and optimization of perioperative surgical management.

Bilateral pseudoangiomatous stromal hyperplasia tumors in axillary male gynecomastia: report of a case.

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferation of breast stromal cells with a complex pattern of interanastomosing spaces lined by myofibroblasts. The exact etiology is still unknown, but a proliferative response of myofibroblasts to hormonal stimuli has been postulated. PASH is a relatively common incidental finding in breast tissue removed for other reasons and rarely manifests as a localized mass. Fewer than 150 cases of tumoral PASH have been reported since it was first described in 1986. Although PASH tends to grow over time, most lesions are cured by surgical excision and the prognosis is excellent. We report an unusual case of bilateral axillary tumoral PASH in a 44-year-old man. Awareness of this disease is important when considering the differential diagnosis of axillary masses. To our knowledge, only one other case of unilateral axillary tumoral PASH in a male patient has been described in English and this is the first case of PASH occurring in male bilateral axillary gynecomastia.

Inflammatory bowel disease is associated with an increased incidence of cardiovascular events.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) present with several extraintestinal manifestations, including systemic inflammation and hypercoagulability. Limited studies have shown that patients with IBD may have a higher risk of developing atherosclerosis. The incidence of coronary artery disease (CAD) and the role of traditional CAD risk factors in IBD patients remain unclear. We sought to compare the rates of CAD events in patients with IBD with matched controls. METHODS: We performed a longitudinal cohort study of patients with IBD compared with matched controls. The primary outcome was the development of CAD events. Traditional and nontraditional CAD risk factors were assessed. Cox proportional hazards model was used to assess the impact of each CAD risk factor on the outcomes. RESULTS: A total of 356 IBD patients and 712 matched controls were followed for a median of 53 and 51 months, respectively. The unadjusted hazard ratio (HR) for developing CAD in the IBD group was 2.85 (95% confidence interval (CI) 1.82-4.46). IBD patients had significantly lower rates of selected traditional CAD risk factors (hypertension, diabetes, dyslipidemia, and obesity; P<0.01 for all). Adjusting for these factors, the HR for developing CAD between groups was 4.08 (95% CI 2.49-6.70). Among nontraditional risk factors, an elevated white blood cell (WBC) count was a risk factor for CAD development in the IBD group (HR 1.23; 95% CI 1.15-1.33). CONCLUSIONS: An increased incidence of CAD events was noted in IBD patients despite having a lower burden of traditional risk factors. Additionally, these risk factors had a lower impact on CAD development in the IBD group. Further investigation into how nontraditional risk factors, including WBC count, and the effect of attenuating systemic inflammation in IBD patients change CAD risk is warranted.

Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model.

Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine-dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions. The present studies tested how TD alters brain pathology in Tg19959 transgenic mice over expressing a double mutant form of the amyloid precursor protein (APP). TD exacerbated amyloid plaque pathology in transgenic mice and enlarged the area occupied by plaques in cortex, hippocampus and thalamus by 50%, 200% and 200%, respectively. TD increased Abeta(1-42) levels by about three fold, beta-CTF (C99) levels by 33% and beta-secretase (BACE1) protein levels by 43%. TD-induced inflammation in areas of plaque formation. Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or Abeta and promotes accumulation of plaques independent of neuron loss or neuritic clusters.

Translocation of amyloid precursor protein C-terminal fragment(s) to the nucleus precedes neuronal death due to thiamine deficiency-induced mild impairment of oxidative metabolism.

Thiamine deficiency (TD) is a model of neurodegeneration induced by mild impairment of oxidative metabolism. TD produces time-dependent glial activation, inflammation, oxidative stress, altered metabolism of amyloid precursor protein (APP), exacerbation of plaque formation from APP, and finally, selective neuron death in specific brain regions. The sub-medial thalamic nucleus (SmTN) is the most sensitive region to TD. Alteration in APP metabolism and nuclear translocation of carboxy-terminal fragments (CTF) of APP has been implicated in neuron death in other models of neurodegeneration. These experiments tested whether TD causes translocation of CTF into the nucleus of neurons in the SmTN that are destined to die after 9 days of TD by examining overlapping immunoreactivity (IR) of antibody APP 369 with either Alz90, 6E10 or 4G8 epitopes in the nuclei of the neurons in the SmTN. TD caused the accumulation of the CTF of APP in nuclei of SmTN neurons within 3 days of TD. These changes did not occur in the cortex which is spared in TD. Western blot analysis of nuclear fractions revealed a significant (61%; P < 0.026) increase in CTF 12 levels in TD SmTN (2.08 +/- 0.56) compared to control SmTN (1.29 +/- 0.41). Although TD increased CTF 15 levels in TD SmTN (1.95 +/- 0.73) compared to control SmTN (0.62 +/- 0.52) by 214%; P < 0.665 and decreased the full-length holo-APP levels in TD SmTN (0.32 +/- 0.30) compared to control SmTN (0.47 +/- 0.18) by 34%; P < 0.753, the differences were statistically insignificant. TD did not alter CTF 15 or CTF 12 levels in cortex. These findings demonstrate that changes in APP metabolism occur in early stages of TD, and they may play an important role in TD-induced selective neuronal loss.