Pregnancy characteristics and outcomes after bariatric surgery: national-level analysis in the United States.

BACKGROUND: Bariatric surgery is an effective surgical treatment for weight reduction in individuals with obesity. Pregnancy outcomes related to prior bariatric surgery are currently under active investigation. OBJECTIVE: To assess national-level trends, characteristics, and outcomes of pregnancy after bariatric surgery in the United States. SETTING: Retrospective cohort study queried the National Inpatient Sample. METHODS: The study population was 14,648,135 patients who had vaginal or cesarean delivery from January 2016 to December 2019. Exposure allocation was based on the history of bariatric surgery. The main outcomes were (1) trends and characteristics related to bariatric surgery, assessed with multivariable binary logistic regression model; and (2) Centers for Disease Control and Prevention-defined severe maternal morbidity, assessed by propensity score matching and generalized estimating equation. RESULTS: A total of 53,950 (.4%) patients had prior bariatric surgery. The number of patients with prior bariatric surgery increased from .3% to .5%, and this trend remained independent in multivariable analysis (P < .001). Patients who had bariatric surgery were also more likely to be older and have obesity, medical co-morbidities, fetal growth restriction, preterm birth, and cesarean delivery compared with those without bariatric surgery (all, P < .05). In a propensity score matched model, patients who had bariatric surgery were more likely to receive blood product transfusion (2.3% versus 1.6%; odds ratio = 1.45; 95% confidence interval, 1.19-1.77), but severe maternal morbidity other than blood product transfusion was comparable to those without (1.1% versus 1.4%; odds ratio = .80; 95% confidence interval, .63-1.02). CONCLUSION: There is a gradual increase of pregnancy after bariatric surgery in recent years in the United States.

Leg Volume in Patients with Lipoedema following Bariatric Surgery.

INTRODUCTION: Lipoedema is characterized as subcutaneous lipohypertrophy in association with soft-tissue pain affecting female patients. Recently, the disease has undergone a paradigm shift departing from historic reiterations of defining lipoedema in terms of classic edema paired with the notion of weight loss-resistant leg volume towards an evidence-based, patient-centered approach. Although lipoedema is strongly associated with obesity, the effect of bariatric surgery on thigh volume and weight loss has not been explored. MATERIAL AND METHODS: In a retrospective cohort study, thigh volume and weight loss of 31 patients with lipoedema were analyzed before and 10-18 and ≥19 months after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Fourteen patients, with distal leg lymphoedema (i.e., with healthy thighs), who had undergone bariatric surgery served as controls. Statistical analysis was performed using a linear mixed-effects model adjusted for patient age and initial BMI. RESULTS: Adjusted initial thigh volume in patients with lipoedema was 23,785.4 mL (95% confidence interval [CI] 22,316.6-25,254.1). Thigh volumes decreased significantly in lipoedema and control patients (baseline vs. 1st follow-up, p < 0.0001 and p = 0.0001; baseline vs. 2nd follow-up, p < 0.0001 and p = 0.0013). Adjusted thigh volume reduction amounted to 33.4 and 37.0% in the lipoedema and control groups at the 1st follow-up, and 30.4 and 34.7% at the 2nd follow-up, respectively (lipoedema vs. control p > 0.999 for both). SG and RYGB led to an equal reduction in leg volume (operation type × time, p = 0.83). Volume reduction was equally effective in obese and superobese patients (weight category × time, p = 0.43). CONCLUSION: SG and RYGB lead to a significant thigh volume reduction in patients with lipoedema.

Putting the Hindgut Hypothesis to the Test in a Diabetic Zucker Rat Model.

BACKGROUND: The hindgut theory hypothesizes a key role of differential hindgut stimulation following metabolic procedures in ameliorating diabetes mellitus. We used two strategies to remove the hindgut from intestinal continuity in order to analyze its impact on diabetes mellitus. METHODS: Loop duodeno-jejunostomy (DJOS) with exclusion of one-third of total intestinal length was performed in 3 groups of 9-week-old Zucker diabetic fatty rats. In group 1, no further alteration of the intestinal tract was made. Group 2 received additional ileal exclusion (IE). Group 3 underwent additional resection of 50% of the ileum with side-to-side ileocecal anastomosis (IR). One, 2, and 4 months after surgery, fasting blood glucose levels, oral glucose tolerance tests (OGTT), and glucose-stimulated hormone analyses were conducted, and bile acid blood levels were compared. Body weight was documented weekly. RESULTS: In relation to DJOS, glucose control was not impaired in IR or IE. On the contrary, only IR could maintain preOP glucose values until 4 months. There were no significant weight differences between the groups. Confirming effective ileal diversion, bile acid blood levels were significantly higher in the DJOS group compared with both IR and IE (p = 0.0025 and p = 0.0047). Operative interventions had no impact on GLP-1 levels at any time point (ANOVA p > 0.05 for all). Insulin secretion was preserved in all groups. CONCLUSION: This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.

The effect of pasireotide on intestinal anastomotic healing with and without whole-body irradiation in a rat model.

OBJECTIVE: To examine pasireotide's effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. MATERIAL AND METHODS: Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. RESULTS: Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. CONCLUSION: Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

Murine genotype impacts pancreatitis severity and systemic inflammation: An experimental study.

BACKGROUND: Little is known regarding the impact of host response in acute pancreatitis. Here, we induce murine necrotizing pancreatitis in 9 different mouse strains. MATERIALS AND METHODS: We examined 9 different mouse strains: Balb/CB4J, C3H/HEJ, NOD/SHILT, A/J, AKR/J, C57BI/6J, DBA/2J, FVB/NJ, 129S1/SvlmJ. 10 animals per strain were randomly allotted to two groups. Sterile necrotizing pancreatitis was induced by injection of taurocholate into the common bile duct. Control animals were injected with saline. Every 6 h, clinical parameters were examined and scored. After 24 h, animals were sacrificed to examine and compare serum enzymes, histology, bronchoalveolar lavage fluid, and serum IL-6. RESULTS: Histologically, taurocholate treated animals scored significantly higher than control animals. Concordantly, serum lipase and amylase were significantly elevated in pancreatitis animals in all strains. NOD/SHILT and AKR/J mice had the highest enzyme activity. 24 h after induction, there were no signs of increased pulmonary vascular leak in taurocholate animals. Remarkably, interleukin 6 was not increased at all in C57BL/6J, C3H/HeJ, and 129S1/SvlmJ mice compared to all other strains. CONCLUSION: The genetic strain has an impact on pancreatitis severity and systemic inflammatory response in a murine taurocholate induction model. Analogous differences in humans may partially account for the disparity in post-ERCP pancreatitis.

Organ-specific monocyte activation in necrotizing pancreatitis in mice.

BACKGROUND: Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory response syndrome. We investigated the underlying changes of monocytes using different activation markers. MATERIALS AND METHODS: A retrograde injection of 2 mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice induced NAP, whereas sham-operated animals (SOP) were treated with saline. After 6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin 6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid were examined. Isolation of mononuclear cells from the blood, spleen, and liver and the subsequent determination of macrophages (F4/80) and their activation marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell sorting (FACS analyses). RESULTS: After pancreatitis induction, pancreatic enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P < 0.001) and histologic pancreatic damage (SOP 0.80 ± 1.92, NAP 19.6 ± 0.64, P < 0.001) developed instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h after onset (6 h albumin SOP 132.0 ± 12.0 µg/mL, NAP 267.2 ± 49.6 µg/mL; P < 0.05; MPO SOP 0.23 ± 0.20 ng/mL, NAP 11.29 ± 3.12 ng/mL, P < 0.01). Blood levels of interleukin 6 increased after 12-24 h (12 h SOP 584 ± 300 pg/mL; NAP 2169 ± 942 pg/mL, P < 0.05), whereas monocytes increased fourfold within 48 h (P < 0.05). Furthermore, pancreatitis increased the percentage of activated monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b 51,654%/82,146%). Similar observations were made for monocytes from the liver and spleen. CONCLUSIONS: Although inflammatory mediators increased during 24 h after pancreatitis induction, monocyte activation lasted for at least 48 h. The latter is not limited to blood but also detected in isolated liver and spleen monocytes.

Retrospective analyses of trends in pancreatic surgery: indications, operative techniques, and postoperative outcome of 1,120 pancreatic resections.

BACKGROUND: Hospital volume, surgeons' experience, and adequate management of complications are factors that contribute to a better outcome after pancreatic resections. The aim of our study was to analyze trends in indications, surgical techniques, and postoperative outcome in more than 1,100 pancreatic resections. METHODS: One thousand one hundred twenty pancreatic resections were performed since 1994. The vast majority of operations were performed by three surgeons. Perioperative data were documented in a pancreatic database. For the purpose of our analysis, the study period was sub-classified into three periods (A 1994 to 2001/n = 363; B 2001 to 2006/n = 305; C since 2007 to 2012/n = 452). RESULTS: The median patient age increased from 51 (A) to 65 years (C; P < 0.001). Indications for surgery were pancreatic/periampullary cancer (49%), chronic pancreatitis (CP; 33%), and various other lesions (18%). About two thirds of the operations were pylorus-preserving pancreaticoduodenectomies. The frequency of mesenterico-portal vein resections increased from 8% (A) to 20% (C; P < 0.01). The overall mortality was 2.4% and comparable in all three periods (2.8%, 2.0%, 2.4%; P = 0.8). Overall complication rates increased from 42% (A) to 56% (C; P < 0.01). CONCLUSIONS: Mortality remained low despite a more aggressive surgical approach to pancreatic disease. An increased overall morbidity may be explained by more clinically relevant pancreatic fistulas and better documentation.

The chemokine ligand CXCL16 is an indicator of bacterial infection in necrotizing pancreatitis.

OBJECTIVES: Current guidelines tell us that intervention in severe necrotizing pancreatitis ought to be performed as late as possible. However, when pancreatic necrosis becomes infected, the necrotic tissue needs to be removed. Unfortunately, bacterial infection can only be proven by invasive methods. METHODS: Necrotizing pancreatitis with sterile or infected necrosis was induced in mice. Mice serum samples were examined by antibody-based protein array. After identifying candidate proteins that showed strong regulation, the serum concentration of these proteins was examined by sandwich ELISA. Then, human serum samples were collected from patients with mild pancreatitis, severe pancreatitis with and without pancreatic necrosis and patients with microbiologically proven infection of pancreatic necrosis. These serum samples were then analyzed by sandwich ELISA. RESULTS: In mice 6 proteins were strongly up-regulated and were further investigated by ELISAs. Of these proteins, CXCL16 and TRANCE (RANKL) concentrations were analyzed in human serum samples. CXCL16 and TRANCE were increased in patients with pancreatic necrosis and abdominal infection. Receiver operated characteristics showed that CXCL16 was superior in predicting infected pancreatic necrosis when compared to C-reactive protein and TRANCE. CONCLUSIONS: Serum CXCL16 is increased in severe pancreatitis with infected pancreatic necrosis and identifies patients who benefit from surgical necrosectomy.

Searching for the molecular benchmark of physiological intestinal anastomotic healing in rats: an experimental study.

PURPOSE: This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. METHODS: In eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The healthy intestinal tissue resected for this operation was used as a control. On days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and perianastomotic segments were examined with an Affymetrix microarray chip to assess changes in gene regulation. Microarray findings were validated using real-time PCR for selected genes. In addition to screening global gene expression, we identified genes intensely regulated during healing and also subjected our data sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto Encyclopedia for Genes and Genomes (KEGG). RESULTS: Compared to the control group, we observed that the number of differentially regulated genes peaked on day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to 1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13 showed not only identical transcription patterns but also analogous regulation intensity. When setting the cutoff of upregulation at 10-fold to identify genes likely to be relevant, the total gene count was significantly lower with 55, 45 and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories were significantly overrepresented during anastomotic healing. Furthermore, 23 overrepresented KEGG pathways were identified. CONCLUSION: This study is the first of its kind that focuses explicitly on gene transcription during intestinal anastomotic healing under standardized conditions. Our work sets a foundation for further studies toward a more profound understanding of the physiology of anastomotic healing.

Dissecting the effect of moxifloxacin in mice with infected necrosis in taurocholate induced necrotizing pancreatitis.

OBJECTIVES: To investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events. METHODS: Sterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10(8) CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS. RESULTS: Moxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10(7) ± 2.4·10(7) vs. AN 4.9·10(4) ± 2.6·10(4) CFU/g; p < 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p < 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p < 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p < 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis. CONCLUSION: In the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.