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1.
BMJ Open ; 14(6): e079217, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862221

RESUMEN

OBJECTIVES: To investigate the association of parental obesity (PO) with onset of obesity, pre-surgical disease duration and body mass index (BMI) at the time of surgery in patients undergoing metabolic-bariatric surgery (MBS). DESIGN: This is a cohort study of the German StuDoQ registry for metabolic-bariatric diseases. All surgical cases from initiation of the registry in September 2015 until August 2020 were screened for pertinent information. SETTING: The registry is based on participating German hospitals of various sizes. PARTICIPANTS: A total of 11 891 patients were included in this analysis, 74.2% of which were females and 25.8% males. Roux-en-Y gastric bypass was performed in 5652 (47.5%) cases, sleeve gastrectomy in 4618 (38.8%) cases and one-anastomosis gastric bypass in 1621 (13.6%) cases. RESULTS: One-sided and two-sided PO are independently associated with early-onset obesity (OR 1.61, [95% CI, 1.47 to 1.76], p<0.001 and OR 2.45, [95% CI, 2.22 to 2.71], p<0.001) and prolonged pre-surgical disease duration (regression coefficient 2.39, [95% CI, 1.93 to 2.83], p<0.001 and regression coefficient 4.27, [95% CI, 3.80 to 4.75], p<0.001). Unlike one-sided PO, two-sided PO had a significant association with BMI at the time of surgery (regression coefficient 0.49, [95% CI, 0.14 to 0.85], p=0.006). Age at the onset of obesity and disease duration had a negative association with BMI at the time of surgery (regression coefficient -0.13, [95% CI, -0.14 to -0.11], p<0.001 and regression coefficient -0.05, [95% CI, -0.07 to -0.04], p<0.001). CONCLUSIONS: This study established a clear association between PO status of patients undergoing MBS and their pre-surgical patient profile as well as known risk factors for poor postoperative response.


Asunto(s)
Cirugía Bariátrica , Índice de Masa Corporal , Sistema de Registros , Humanos , Masculino , Femenino , Alemania/epidemiología , Adulto , Obesidad/cirugía , Padres , Persona de Mediana Edad , Estudios de Cohortes , Adolescente , Adulto Joven
2.
Obes Surg ; 34(7): 2446-2453, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38769237

RESUMEN

INTRODUCTION: With a rising number of bariatric procedures, the absolute number of postoperative complications is increasing, too. Postoperative bleeding, particularly along the staple line, is a recognized challenge. Numerous strategies including reinforcement of the staple line (SLR) have been proposed to improve bleeding rates, but no single technique has shown superiority over the others. In our bariatric center, we have implemented intraoperative blood pressure regulation alone, without SLR, to reduce hemorrhagic complications postoperatively. METHODS: This retrospective observational analysis compares the incidence of postoperative bleeding in two groups of consecutive patients (total n = 438 patients), one with and one without intraoperative blood pressure elevation to 150 mmHg systolic without the additional use of staple line reinforcement. This intervention was integrated into our standard bariatric surgical procedure, no randomization or matching was conducted. Significant postoperative bleeding was defined as drop of hemoglobin of more than 2.5 mg/dl in 48 h and one of the following symptoms: lactate ≥ 2 mmol/L, bloody drainage, quantity of drainage more than 200 ml and/or radiological signs. RESULTS: Defined postoperative bleeding occurred in 33 (7.5%) patients. We observed a decrease in bleeding rates from 10% to 5% (n = 22 vs. n = 11) after introducing intraoperative blood pressure increase (p = 0.034). The rate of revisional surgery for bleeding also decreased from 2.7% to 0.5% (n = 6 vs. n = 1). In multivariate analysis, the intervention with blood pressure elevation showed a significant decrease on bleeding rates (p = 0.038). CONCLUSION: The use of increased intraoperative blood pressure alone, without staple line reinforcement, appears to be an effective and suitable method for reducing post-bariatric hemorrhagic complications.


Asunto(s)
Cirugía Bariátrica , Presión Sanguínea , Obesidad Mórbida , Hemorragia Posoperatoria , Humanos , Estudios Retrospectivos , Femenino , Masculino , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/prevención & control , Persona de Mediana Edad , Adulto , Obesidad Mórbida/cirugía , Cirugía Bariátrica/métodos , Grapado Quirúrgico , Incidencia , Resultado del Tratamiento , Cuidados Intraoperatorios/métodos , Reoperación/estadística & datos numéricos
3.
Transpl Int ; 37: 12263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550626

RESUMEN

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.


Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Factores de Riesgo , Rechazo de Injerto , Supervivencia de Injerto , Donadores Vivos
4.
Obes Surg ; 34(2): 310-317, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38109013

RESUMEN

PURPOSE: Banded sleeve gastrectomy (BSG) has been shown to enable better weight loss than non-banded sleeve gastrectomy (SG) in retrospective analyses. These findings were supported by two randomized controlled trials (RCT). However, to date, mid-term prospective data is not available. MATERIALS AND METHODS: We invited all 94 patients of an RCT comparing banded to non-banded sleeve gastrectomy at 3 years (DRKS00007729) for a 5-year follow-up visit. Eighty-two patients (BSG n = 42; SG n = 40) came for evaluation. Outcome measures were identical with the RCT to allow longitudinal comparison. Data analysis was descriptive and focused on biometric data, development of comorbidities, mid-term complications, quality of life, and type of body contouring surgery (BCS). RESULTS: The per-protocol analysis revealed a treatment difference of 9% (CI - 1.5 to 19.6) excess weight loss (EWL). Total weight loss (TWL) was 27.4% (CI 23.5-31.3) after SG and 31.6% (CI 27.3-35.5) after BSG. Twenty percent of patients after SG and 11.9% following BSG had been converted to a gastric bypass. Type 2 diabetes went into remission in most patients (SG 66.7% vs. BSG 63.6%). Antihypertensive medication was stopped or reduced in 81.3% after SG and 80% after BSG. Reflux symptoms were similar in both groups (symptoms [Formula: see text] 1/ week: SG 28.2% vs. BSG 26.8%). Frequency of postprandial regurgitation was higher after BSG (SG 23% vs. BSG 59%). Forty percent of patients had undergone BCS at time of follow-up. CONCLUSION: Five-year weight loss after BSG was 9% EWL and 4.2% TWL higher compared to SG. The main added morbidity following BSG was postprandial regurgitation.


Asunto(s)
Derivación Gástrica , Gastroplastia , Obesidad Mórbida , Humanos , Obesidad Mórbida/cirugía , Derivación Gástrica/métodos , Gastroplastia/métodos , Estudios Retrospectivos , Gastrectomía/métodos , Pérdida de Peso , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Sci Rep ; 13(1): 13401, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37591977

RESUMEN

Obesity is a chronic, multifactorial disease which is linked to a number of adverse endocrinological and metabolic conditions. Currently, bariatric surgery is one of the most effective treatments for individuals diagnosed with severe obesity. However, the current indications for bariatric surgery are based on inadequate metrics (i.e., BMI) which do not account for the complexity of the disease, nor the heterogeneity among the patient population. Moreover, there is a lack of understanding with respect to the biological underpinnings that influence successful and sustained weight loss post-bariatric surgery. Studies have implicated age and pre-surgery body weight as two factors that are associated with favorable patient outcomes. Still, there is an urgent medical need to identify other potential factors that could improve the specificity of candidate selection and better inform the treatment plan of patients with obesity. In this report, we present and describe the cohort of the DECON pilot project, a multicenter study which aims to identify predictive biomarkers of successful weight loss after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Obesidad Mórbida , Humanos , Proyectos Piloto , Obesidad/cirugía , Obesidad Mórbida/cirugía , Pérdida de Peso
6.
Obes Surg ; 33(5): 1519-1527, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36856989

RESUMEN

INTRODUCTION: Parental predisposition and age of onset may be independently associated with 1-year total weight loss (TWL) failure (< 20%) after metabolic-bariatric surgery (MBS). METHODS: This cohort study includes all cases of the German StuDoQ|MBE register (2015-2019) with data on parental predisposition, obesity onset, and at least 1-year follow up after primary MBS procedures (n = 14,404). We provide descriptive statistics of the cohort in terms of the main outcome and 1-year TWL failure, and provide characteristics of surgery type subgroups. Finally, we provide a multivariate logistic regression model of 1-year TWL failure. RESULTS: 58.8% and 45.7% of patients reported maternal and paternal predisposition for obesity, respectively. Average onset of obesity was 15.5 years and duration of disease 28.3 years prior to MBS. SG is the most frequently performed procedure (47.2%) followed by RYGB (39.7%) and OAGB (13.1%). Mean 1-year TWL is 32.7 ± 9.3%, and 7.8% (n = 1,119) of patients show TWL failure (< 20%). Multivariate analysis shows independent association of early onset of obesity (< 18 years), male sex, age at operation, pre-operative BMI, pre-operative weight loss, sleeve gastrectomy (SG), and type 2 diabetes (T2D) with 1-year TWL failure (p < 0.001). CONCLUSION: The proportions of MBS patients that report on paternal and maternal predisposition for obesity are 45.7% and 58.8% respectively, and average age at onset is 15.5 years. 7.8% of patients do not meet current target criteria of successful response to surgery at 1 year. Early onset, male sex, age at operation, pre-operative BMI, pre-operative weight loss, SG, and T2D are independently associated with weight loss failure.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Derivación Gástrica , Obesidad Mórbida , Humanos , Masculino , Adolescente , Obesidad Mórbida/cirugía , Estudios de Cohortes , Diabetes Mellitus Tipo 2/cirugía , Edad de Inicio , Resultado del Tratamiento , Estudios Retrospectivos , Obesidad/cirugía , Cirugía Bariátrica/métodos , Pérdida de Peso/fisiología , Padres , Gastrectomía/métodos , Derivación Gástrica/métodos
7.
Surg Obes Relat Dis ; 19(4): 364-373, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36470811

RESUMEN

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.


Asunto(s)
Cirugía Bariátrica , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Estados Unidos/epidemiología , Estudios Retrospectivos , Resultado del Embarazo , Obesidad/cirugía
8.
J Vis Exp ; (184)2022 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-35786676

RESUMEN

Obesity is a complex disease influenced by genetics, epigenetics, the environment, and their interactions. Mature adipocytes represent the major cell type in white adipose tissue. Understanding how adipocytes function and respond to (epi)genetic and environmental signals is essential for identifying the cause(s) of obesity. RNA and chromatin have previously been isolated from adipocytes using enzymatic digestion. In addition, protocols have been developed for nuclear isolation, where purification is achieved by fluorescence-activated cell sorting (FACS) of adipocyte-specific transgenic reporters. One of the greatest challenges to achieving high yield and quality during such protocols is the substantial amount of lipid contained in adipose tissue. The present protocol describes an optimized procedure for isolating mature adipocytes that leverages heptane to separate lipids from the targets of interest (RNA/chromatin). The resulting RNA has high integrity and generates high-quality RNA-seq results. Likewise, the procedure improves nuclei yield rate and generates reproducible ChIP-seq results across samples. Therefore, the current study provides a reliable and universal murine adipocyte isolation protocol suitable for whole-genome transcriptome and epigenome studies.


Asunto(s)
Adipocitos Blancos , Transcriptoma , Animales , Cromatina/metabolismo , Epigenoma , Ratones , Obesidad/metabolismo , ARN/metabolismo
9.
Obes Surg ; 32(6): 1980-1989, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35384574

RESUMEN

BACKGROUND: Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas. MATERIALS AND METHODS: We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness. RESULTS: DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham. CONCLUSION: In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis.


Asunto(s)
Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Animales , Inteligencia Artificial , Glucemia/metabolismo , Proliferación Celular , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Insulina , Yeyuno/cirugía , Masculino , Obesidad Mórbida/cirugía , Páncreas/metabolismo , Páncreas/cirugía , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Zucker
10.
Dtsch Arztebl Int ; 119(5): 70-80, 2022 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-34819222

RESUMEN

BACKGROUND: In 2017, the prevalence of obesity (BMI ≥= 30 kg/m2) in Germany was approximately 16%. Obesity increases an individual's risk of developing type 2 diabetes (T2DM) and arterial hypertension; it also increases overall mortality. Consequently, effective treatment is a necessity. Approximately 20 000 bariatric operations are performed in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane databases and on current German clinical practice guidelines. RESULTS: The types of obesity surgery most commonly performed in Germany, Roux-en-Y gastric bypass and sleeve gastrectomy, lead to an excess weight loss of 27-69% ≥= 10 years after the procedure. In obese patients with T2DM, the diabetes remission rate ≥= 10 years after these procedures ranges from 25% to 62%. Adjusted regression analyses of data from large registries have shown that the incidence of malignancies is 33% lower in persons who have undergone obesity surgery compared to control subjects with obesity (unadjusted incidence 5.6 versus 9.0 cases per 1000 person-years). The operation can cause vitamin deficiency, surgical complications, gastroesophageal reflux, and dumping syndrome. Therefore, lifelong follow-up is necessary. CONCLUSION: In view of an increasing number of patients undergoing bariatric surgery, it will probably not be feasible in the future for lifelong follow-up to be provided exclusively in specialized centers.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Cirugía Bariátrica/métodos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Derivación Gástrica/métodos , Humanos , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Obesidad Mórbida/cirugía , Resultado del Tratamiento
11.
Arterioscler Thromb Vasc Biol ; 41(10): 2563-2574, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34348490

RESUMEN

Objective: The accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We previously reported that a genetic deficiency of the intracellular signaling adaptor TRAF5 (TNF [tumor necrosis factor] receptor-associated factor 5) accelerates atherosclerosis in mice by increasing inflammatory cell recruitment. Here, we tested the hypothesis that an impairment of TRAF5 signaling modulates adipose tissue inflammation and its metabolic complications in a model of diet-induced obesity in mice. Approach and Results: To induce diet-induced obesity and adipose tissue inflammation, wild-type or Traf5-/- mice consumed a high-fat diet for 18 weeks. Traf5-/- mice showed an increased weight gain, impaired insulin tolerance, and increased fasting blood glucose. Weight of livers and peripheral fat pads was increased in Traf5-/- mice, whereas lean tissue weight and growth were not affected. Flow cytometry of the stromal vascular fraction of visceral adipose tissue from Traf5-/- mice revealed an increase in cytotoxic T cells, CD11c+ macrophages, and increased gene expression of proinflammatory cytokines and chemokines. At the level of cell types, expression of TNF[alpha], MIP (macrophage inflammatory protein)-1[alpha], MCP (monocyte chemoattractant protein)-1, and RANTES (regulated on activation, normal T-cell expressed and secreted) was significantly upregulated in Traf5-deficient adipocytes but not in Traf5-deficient leukocytes from visceral adipose tissue. Finally, Traf5 expression was lower in adipocytes from obese patients and mice and recovered in adipose tissue of obese patients one year after bariatric surgery. Conclusions: We show that a genetic deficiency of TRAF5 in mice aggravates diet-induced obesity and its metabolic derangements by a proinflammatory response in adipocytes. Our data indicate that TRAF5 may promote anti-inflammatory and obesity-preventing signaling events in adipose tissue.


Asunto(s)
Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Linfocitos/metabolismo , Obesidad/metabolismo , Paniculitis/metabolismo , Factor 5 Asociado a Receptor de TNF/deficiencia , Adipocitos/inmunología , Adipocitos/patología , Tejido Adiposo/inmunología , Tejido Adiposo/patología , Adiposidad , Adulto , Anciano , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Femenino , Humanos , Linfocitos/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Obesidad/genética , Obesidad/inmunología , Obesidad/patología , Paniculitis/genética , Paniculitis/inmunología , Paniculitis/patología , Transducción de Señal , Factor 5 Asociado a Receptor de TNF/genética
12.
Visc Med ; 37(3): 206-211, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34250078

RESUMEN

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.

14.
Nature ; 592(7854): 444-449, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33762736

RESUMEN

Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer1,2. The accumulation of metabolites leads to cell stress and inflammation in the liver3, but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displays key features of human NASH (hereafter, NASH mice), we found an indispensable role for T cells in liver immunopathology. We detected the hepatic accumulation of CD8 T cells with phenotypes that combined tissue residency (CXCR6) with effector (granzyme) and exhaustion (PD1) characteristics. Liver CXCR6+ CD8 T cells were characterized by low activity of the FOXO1 transcription factor, and were abundant in NASH mice and in patients with NASH. Mechanistically, IL-15 induced FOXO1 downregulation and CXCR6 upregulation, which together rendered liver-resident CXCR6+ CD8 T cells susceptible to metabolic stimuli (including acetate and extracellular ATP) and collectively triggered auto-aggression. CXCR6+ CD8 T cells from the livers of NASH mice or of patients with NASH had similar transcriptional signatures, and showed auto-aggressive killing of cells in an MHC-class-I-independent fashion after signalling through P2X7 purinergic receptors. This killing by auto-aggressive CD8 T cells fundamentally differed from that by antigen-specific cells, which mechanistically distinguishes auto-aggressive and protective T cell immunity.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Hígado/inmunología , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/patología , Receptores CXCR6/inmunología , Acetatos/farmacología , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/patología , Muerte Celular/efectos de los fármacos , Muerte Celular/inmunología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Humanos , Interleucina-15/inmunología , Interleucina-15/farmacología , Hígado/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL
15.
Ann Surg ; 272(5): 690-695, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32657920

RESUMEN

OBJECTIVE: The aim of this study was to compare silicone-banded sleeve gastrectomy (BSG) to nonbanded sleeve gastrectomy (SG) regarding weight loss, obesity-related comorbidities, and complications. SUMMARY BACKGROUND DATA: As a primary bariatric procedure, SG leads to excellent weight loss, yet weight regain is a relevant issue in mid- to long-term follow-up. Retrospective analyses suggest that banding a sleeve using a silicone ring may decrease weight regain and improve weight loss. METHODS: The banded versus nonbanded sleeve gastrectomy single-center, randomized controlled trial was conducted from January 2015 to August 2019. The primary endpoint was defined as excess weight loss 3 years after surgery. Secondary endpoints included the surgery's impact on obesity-related comorbidities, quality of life, and complications. The study was registered under DRKS00007729. RESULTS: Among 94 patients randomized, 97% completed 3-year follow-up. Mean initial body mass index was 50.9 kg/m [95% confidence interval (CI), 49.6-52.2]. Mean adjusted excess weight loss 3 years after SG amounted to 62.3% (95% CI, 56.2-68.5) and 73.9% ( 95% CI, 67.8-80.0) after BSG (difference 11.6%, P = 0.0073). Remission of type 2 diabetes occurred in 66.7% (4/6) after SG and in 91.0% (10/11) following BSG (P = 0.21). Three years after surgery, ring implantation correlated with decreased frequency of symptomatic reflux episodes (P = 0.01) but increased frequency of regurgitation (P = 0.03). The rate of major complications was not different between the study groups (BSG, n = 3; SG, n = 2; P = 0.63). Quality of life was better following BSG (P = 0.001). CONCLUSIONS: BSG provided better weight loss than nonbanded SG 3 years after surgery. Regurgitation was the main clinically relevant negative effect after BSG.


Asunto(s)
Gastrectomía/métodos , Obesidad Mórbida/cirugía , Adulto , Comorbilidad , Femenino , Estudios de Seguimiento , Alemania , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Calidad de Vida , Siliconas
17.
Obes Surg ; 29(12): 4000-4007, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31367988

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/cirugía , Intolerancia a la Glucosa/etiología , Intestino Delgado/cirugía , Animales , Ácidos y Sales Biliares/sangre , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Experimental/etiología , Duodeno/metabolismo , Duodeno/cirugía , Péptido 1 Similar al Glucagón/sangre , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/diagnóstico , Prueba de Tolerancia a la Glucosa , Íleon/metabolismo , Íleon/cirugía , Insulina/sangre , Intestino Delgado/metabolismo , Yeyuno/metabolismo , Yeyuno/cirugía , Masculino , Distribución Aleatoria , Ratas , Ratas Zucker
18.
Surg Obes Relat Dis ; 15(8): 1233-1238, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31285129

RESUMEN

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) achieves excellent weight loss, yet recent reports indicate weight regain in a substantial number of patients. OBJECTIVES: Inserting a nonadjustable gastric band may improve weight loss after SG. SETTING: University Hospital, Germany. METHODS: In a retrospective matched-pair analysis 51 patients who underwent banded SG (BSG) using a silicone ring between November 2010 and May 2017 were compared with patients who underwent conventional SG regarding weight loss, complications, and co-morbidity. Median follow-up was 5 years. RESULTS: Total weight loss was equal in the early follow-up (P = .118 and P = .111) but significantly better in BSG 3 and 5 years after surgery (BSG versus SG at 3 yr 38.7% ± 7.8, n = 33 versus 31.9 ± 10.7, n = 33, P = .002; BSG versus SG at 5 yr 37.6% ± 8.5, n = 27 versus 29.5 ± 12.9, n = 23, P = .008). Ring placement had no significant impact on clinical reflux signs (Fisher's exact test P > .999), yet 37 % of BSG patients reported ≥1 regurgitation per week (Fisher's exact test P = .013, odds ratio 12.4). CONCLUSION: BSG leads to better weight loss than nonbanded SG 5 years after surgery. This comes at the expense of a higher rate of regurgitation. At a time in which weight loss limitations of a stand-alone SG are becoming a clinical problem, banding the sleeve may be a strategy to improve weight loss with this procedure.


Asunto(s)
Gastrectomía , Pérdida de Peso/fisiología , Adulto , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Gastrectomía/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
19.
J Surg Res ; 239: 201-207, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30851519

RESUMEN

BACKGROUND: Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. MATERIALS AND METHODS: Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. RESULTS: Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. CONCLUSIONS: RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.


Asunto(s)
Fuga Anastomótica/patología , Transfusión de Componentes Sanguíneos/efectos adversos , Intestinos/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/cirugía , Femenino , Estudios de Seguimiento , Humanos , Intestinos/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Reoperación , Factores de Riesgo , Inhibidor Tisular de Metaloproteinasa-2/análisis , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Adulto Joven
20.
Int J Colorectal Dis ; 34(2): 337-345, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30483864

RESUMEN

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.


Asunto(s)
Intestinos/patología , Intestinos/cirugía , Somatostatina/análogos & derivados , Irradiación Corporal Total , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Causas de Muerte , Modelos Animales de Enfermedad , Granulocitos/metabolismo , Inyecciones , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Complicaciones Posoperatorias/etiología , Presión , Ratas Wistar , Somatostatina/administración & dosificación , Somatostatina/farmacología , Adherencias Tisulares/patología
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