Tissue-specific inflammation and insulin sensitivity in subjects with obesity.

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship. The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements. Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health.

Clinical implementation of a fully automated quantitative perfusion cardiovascular magnetic resonance imaging workflow with a simplified dual-bolus contrast administration scheme.

This study clinically implemented a ready-to-use quantitative perfusion (QP) cardiovascular magnetic resonance (QP CMR) workflow, encompassing a simplified dual-bolus gadolinium-based contrast agent (GBCA) administration scheme and fully automated QP image post-processing. Twenty-five patients with suspected obstructive coronary artery disease (CAD) underwent both adenosine stress perfusion CMR and an invasive coronary angiography or coronary computed tomography angiography. The dual-bolus protocol consisted of a pre-bolus (0.0075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) and a main bolus (0.075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) at an infusion rate of 3 ml/s. The arterial input function curves showed excellent quality. Stress MBF ≤ 1.84 ml/g/min accurately detected obstructive CAD (area under the curve 0.79; 95% Confidence Interval: 0.66 to 0.89). Combined visual assessment of color pixel QP maps and conventional perfusion images yielded a diagnostic accuracy of 84%, sensitivity of 70% and specificity of 93%. The proposed easy-to-use dual-bolus QP CMR workflow provides good image quality and holds promise for high accuracy in diagnosis of obstructive CAD. Implementation of this approach has the potential to serve as an alternative to current methods thus increasing the accessibility to offer high-quality QP CMR imaging by a wide range of CMR laboratories.

The usefulness of tumor necrosis factor-like weak inducer of apoptosis in patients with acute ST-elevation myocardial infarction.

OBJECTIVE: We aimed to determine the utility of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) for the early diagnosis and prognosis of acute ST-elevation myocardial infarction (STEMI). PATIENTS AND METHODS: Patients presented with STEMI arrived at the hospital within 45 minutes after the onset of chest pain were included in this study. Blood samples for TWEAK, high-sensitivity C-reactive protein (hs-CRP), creatine kinase MB isoenzyme (CK-MB), and high-sensitivity cardiac troponin T (hs-TnT) levels were obtained at the time of arrival at the hospital. Subsequent samples were drawn at 4 h after primary percutaneous coronary intervention. RESULTS: The study cohort comprised patients with confirmed STEMI between January 2022 and September 2022, for a total of 45 enrolled STEMI patients. Plasma TWEAK levels were markedly elevated at hospital arrival, followed by a decrease at 4 hours after successful primary percutaneous coronary revascularization (PPCI). High-sensitive troponin T (Hs-TropT), CK-MB, and CRP were found within normal limits at the hospital arrival. Conversely, increased levels of CRP, CKMB, and hs-TropT were observed at 4 hours after PPCI. CONCLUSIONS: Plasma TWEAK levels were elevated earlier in the acute phase and decreased earlier after PPCI than other classic myocardial biomarkers.

Efficiency based updating of evidence based surgical guidelines - Experiences from a multidisciplinary guideline upon Minimally Invasive Surgery.

Background: Updating evidence-based clinical practice guidelines is an onerous process and there is a call for more efficient determination of key questions that need updating. Especially for surgical techniques it is unclear if new evidence will result in substantial changes after wide implementation and if continuous updating is always necessary. Objectives: This study analyses the impact of updating a surgical guideline and proposes suggestions for optimising this process. Materials and methods: The Dutch Minimally Invasive Surgery guideline was developed in 2011 and updated in 2021. For both versions a multidisciplinary guideline working group (GDG) was created, that determined key questions. Changes in conclusions and recommendations were analysed by the GDG and statements for expected change of recommendations in the future were made. Results: 15 key questions were formed, of which 12 were updates of the previous guideline. For only 27% of the updated key questions, the conclusions changed. In ten years, the body grew only marginally for most key questions and quality of the evidence did not improve substantially for almost all key questions. However, in this first update of the MIC guideline, many recommendations did change due to a more robust interpretation of the conclusions by the GDG. Based on analysis of this updating process, the GDG expects that only four out of 15 recommendations may change in the future. Conclusion: We propose an additional step at the end of guideline development and updating, where the necessity for updating in the future is determined for each key question by the GDG, using their valuable knowledge gained from developing or updating the guideline. For surgical guidelines, the authors suggest updating key issues if it includes a relatively newly introduced surgical- or adapted technique or a new patient group. Low quality or small body of evidence should not be a reason in itself for updating, as this mostly does not lead to new evidence-based conclusions. This new step is expected to result in a more efficient prioritising of key questions that need updating. What's new?: By adding one additional step at the end of the updating process, the future updating process could become more efficient.

A new marker of coronary collateral flow in patients presenting with acute myocardial infarction.

OBJECTIVE: Multimerin-2 is an adhesion substrate between pericytes and basal membranes during angiogenesis. The present study aimed to assess the relationship between serum Multimerin-2 and coronary collateral flow grade. PATIENTS AND METHODS: Between April 2022 and August 2022, 88 patients with subacute ST-elevation myocardial infarction were included in this study. The main inclusion criteria were patients who present 12-48 hours after symptom onset and aged between 18 and 90 years. The patients were divided into two groups according to the Rentrop classification: poor collateral group (Rentrop grade 0-1) and good collateral group (Rentrop grade 2-3). Biochemical and hematological parameters were measured before coronary angiography. RESULTS: Serum Multimerin-2 levels were found to be significantly different between the two groups, and levels were higher in the Rentrop 2-3 group than in the Rentrop 0-1 group (3,527.9 ± 1,194.2 pg/ml and 946.7 ± 249.1 pg/ml; p < 0.00). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.918 (p = 0.001), and the best cut-off value of 849 pg/ml had a sensitivity of 90.1% and a specificity of 84.1% for predicting Rentrop grade 2-3 coronary flow. The number of patients with low left ventricular ejection fraction (LVEF) by echocardiography at 30 days was significantly higher in patients with poor collateralization. CONCLUSIONS: Multimerin-2 levels were found to be higher in patients with Rentrop grade 2-3 coronary flow than Rentrop grade 0-1 coronary flow after myocardial infarction. We detected a potential relationship between MMR-2 and good coronary collateral formation.

Methods for increasing distal radial artery diameter.

OBJECTIVE: Our study aimed to find the maximum rate of increase in distal radial artery size. PATIENTS AND METHODS: Diameter measurements were obtained on transverse and sagittal sections of the artery with a high-frequency linear transducer (Philips ClearVue L12-4 Mhz). In the baseline evaluation, radial artery and distal radial artery diameters were measured. The patients were divided into two groups: patients with flow-mediated dilatation in Group I and patients with 30 mg Topical Nitroglycerin in Group II. Group II patients were divided into two groups 30 minutes after topical nitroglycerin; patients with flow-mediated dilatation (FDM) in Group IIa, patients with wrist warming plus FMD in Group IIb. RESULTS: A significant increase was found between baseline and second measurements in the radial artery (2.64±0.46 and 2.36±0.39 mm; p=0.02 in Group I, 2.78±0.38 and 2.39±0.25 mm; p=0.01 in Group II) and distal radial artery (2.29±0.49 and 1.93±0.37 mm; p=0.02 in Group I, 2.32±0.28 and 1.96±0.44 mm; p=0.04 in Group II) diameters. Radial (3.02±0.55 and 2.78±0.38 mm; p<0.01) and distal radial artery (2.55±0.32 and 2.32±0.28 mm; p=0.01) diameters increased compared to the second measurements in Group IIa. Radial (3.25±0.35 and 2.78±0.38 mm; p<0.01) and distal radial artery (2.88±0.12 and 2.32±0.28 mm; p<0.01) diameters increased compared to the second measurements in Group IIb. The results of the final evaluations of the two groups were compared, radial (3.02±0.55 and 3.25±0.35 mm; p=0.04) and distal radial artery (2.55±0.32 and 2.88±0.12 mm; p=0.03) diameters were found to be significantly higher in Group IIb than Group IIa. When comparing baseline and final evaluations, the radial artery diameter was increased by 37%, and the distal radial artery diameter was increased by 49% in Group IIb. CONCLUSIONS: We increased the radial artery diameter higher proportion than defined in the literature.

Evaluation of CPAP adherence in bariatric patients diagnosed with obstructive sleep apnea: outcomes of a multicenter cohort study.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent but mostly undiagnosed in obese patients scheduled for bariatric surgery. To prevent cardiopulmonary complications, many clinics perform preoperative OSA screening. Consequently, adequate adherence to continuous positive airway pressure (CPAP) therapy is essential but challenging. We aimed to evaluate CPAP adherence and its influence on postoperative outcomes. METHODS: In a prospective multicenter cohort study, we compared different perioperative strategies for handling undiagnosed OSA in bariatric patients. In this subgroup analysis, patients newly diagnosed with OSA were compared to those with pre-existing OSA. We assessed inadequate CPAP adherence, defined as < 4 h/night, between the preoperative period and 6 months postoperative. Cardiopulmonary complications and (un)scheduled ICU admissions were also evaluated. RESULTS: In total, 272 patients with newly diagnosed OSA (67.4%) and 132 patients with pre-existing OSA (32.6%) were included. Before surgery, 41 newly diagnosed patients used CPAP inadequately, compared to 5 patients with pre-existing OSA (15% vs. 4%, p = 0.049). Six months after surgery, inadequate CPAP use increased to 73% for newly diagnosed patients and 39% for patients with pre-existing OSA, respectively (p < 0.001). Incidences of cardiopulmonary complications, scheduled, and unscheduled ICU admissions were similar in the two study groups (p = 0.600, p = 0.972, and p = 0.980, respectively). CONCLUSION: Inadequate CPAP adherence is higher in bariatric patients newly diagnosed with OSA when compared to patients with pre-existing OSA. Strategies to increase CPAP adherence may be valuable when considering routine OSA screening and CPAP therapy in patients undergoing bariatric surgery. Further studies are needed to improve current guidelines on perioperative OSA management of obese patients. TRIAL REGISTRATION: POPCORN study, registered at Netherlands Trial Register, https://www.trialregister.nl/trial/6805 . ID no: 6805.

Resizing a large pouch after laparoscopic Roux-en-Y gastric bypass: comparing the effect of two techniques on weight loss.

BACKGROUND: Insufficient weight loss or weight regain has many causes including a large gastric pouch. A large gastric pouch may be due to the surgical technique or can be patient related (dilation). Resizing the gastric pouch may lead to additional weight loss. Currently, there is no gold standard for the revisional surgical technique. Therefore this study was performed to determine which surgical technique for revisional bariatric surgery (BS) has superior outcomes in terms of weight loss: sleeve resection of the gastrojejunostomy and gastric pouch (SGP), or resection of the gastrojejunostomy with resizing of the pouch and creation of a new anastomosis (RGJ). METHODS: All patients who underwent revisional BS for insufficient weight loss or weight regain as a result of an enlarged pouch after LRYGB from April 2014 to June 2018 in our hospitals were included in this observational cohort study. Outcomes were measured in percentage total weight loss (%TWL). RESULTS: A total of 37 patients who underwent SGP and 21 patients who underwent RGJ as revisional BS were included in this study. The median body mass index before revisional BS was 37.6 kg/m2 versus 35.7 kg/m2 (SGP vs RGJ, respectively, P = 0.115). There was no significant difference in %TWL between the two cohorts 1 and 2 years after revisional BS, respectively; SGP 14.5% vs RGJ 11.0%, P = 0.885 and SGP 12.3% vs RGJ 10.8%, P = 0.604. Comparing %TWL based on weight at LRYGB, there was also no significant difference two years after revisional BS (SGP 22.0% vs RGJ 22.2%, P = 0.885). The average use of surgical disposables for the SGP technique were lower compared to the RGJ technique. CONCLUSIONS: Resizing a large pouch leads to additional weight loss. Both techniques have comparable outcomes in terms of weight loss. However, based on average surgical costs, the SGP technique may be preferable.

Locoregional recurrences after transanal total mesorectal excision of rectal cancer during implementation.

BACKGROUND: Transanal total mesorectal excision (TaTME) has been proposed as an approach in patients with mid and low rectal cancer. The TaTME procedure has been introduced in the Netherlands in a structured training pathway, including proctoring. This study evaluated the local recurrence rate during the implementation phase of TaTME. METHODS: Oncological outcomes of the first ten TaTME procedures in each of 12 participating centres were collected as part of an external audit of procedure implementation. Data collected from a cohort of patients treated over a prolonged period in four centres were also collected to analyse learning curve effects. The primary outcome was the presence of locoregional recurrence. RESULTS: The implementation cohort of 120 patients had a median follow up of 21·9 months. Short-term outcomes included a positive circumferential resection margin rate of 5·0 per cent and anastomotic leakage rate of 17 per cent. The overall local recurrence rate in the implementation cohort was 10·0 per cent (12 of 120), with a mean(s.d.) interval to recurrence of 15·2(7·0) months. Multifocal local recurrence was present in eight of 12 patients. In the prolonged cohort (266 patients), the overall recurrence rate was 5·6 per cent (4·0 per cent after excluding the first 10 procedures at each centre). CONCLUSION: TaTME was associated with a multifocal local recurrence rate that may be related to suboptimal execution rather than the technique itself. Prolonged proctoring, optimization of the technique to avoid spillage, and quality control is recommended.

ANTECEDENTES: La escisión total del mesorrecto por vía transanal (Transanal Total Mesorectal Excision, TaTME) se ha propuesto como abordaje quirúrgico en pacientes con cáncer de recto medio e inferior. La técnica TaTME se ha introducido en los Países Bajos mediante un proceso de formación estructurado que incluye la supervisión. Este estudio evaluó el porcentaje de recidiva local durante la fase de implementación de TaTME. MÉTODOS: Se recogieron los resultados oncológicos de los primeros 10 procedimientos realizados mediante TaTME en cada uno de los 12 centros participantes como parte de una auditoría externa de implementación del procedimiento. Se reunió una cohorte más amplia de pacientes procedentes de 4 centros para analizar los efectos de la curva de aprendizaje. El criterio de valoración principal fue la presencia de recidiva locorregional. RESULTADOS: La cohorte de implementación de 120 pacientes tuvo una mediana de seguimiento de 21,9 meses. Los resultados a corto plazo incluyeron una tasa del margen de resección circunferencial positivo del 5% y una tasa de fuga anastomótica del 17,4%. La tasa global de recidiva local en la cohorte de implementación fue del 10% (12/120) con un intervalo medio de recidiva de 15,2 (DE 7) meses. El patrón de recidiva local fue multifocal en 8 de 12 casos (67%). En la cohorte ampliada (n = 266), la tasa global de recidiva fue del 5,6% (4,0%, excluyendo a los primeros 10 pacientes). CONCLUSIÓN: TaTME se asoció con un porcentaje de recidiva local multifocal que puede relacionarse con una ejecución subóptima, más que con la técnica en sí. Se recomienda una supervisión prolongada, la optimización de la técnica para evitar la diseminación tumoral, así como un control de calidad.

[Mesenteric venous thrombosis during pregnancy; a rare cause of acute ischaemia of the small intestine]. / Veneuze mesenteriale trombose tijdens de zwangerschap.

BACKGROUND: Acute ischaemia of the small intestine is caused by mesenteric venous thrombosis in 5-15% of patients. The non-specific symptoms frequently lead to a diagnostic delay. CASE DESCRIPTION: A 30-year-old pregnant woman presented at the accident and emergency department with progressive abdominal pain, nausea and vomiting. During admission the patient developed signs of peritonitis. Diagnostic laparoscopy revealed a picture of mesenteric venous thrombosis, and we resected 170 cm ischemic small intestine. No underlying cause was identified, apart from the pregnancy. The patient was treated with low-molecular-weight heparin and later gave birth to a healthy child. CONCLUSION: If a patient presents with (unexplained) progressive abdominal symptoms and disproportional abdominal pain without peritonitis, the possibility of intestinal ischaemia should be considered during differential diagnosis.

Ruptured hepatic artery aneurysm: an unusual presentation of polyarteritis nodosa.

A 52-year-old woman presented with severe acute right upper quadrant abdominal pain and signs of intra-abdominal haemorrhage. CT and selective angiography revealed a ruptured right hepatic artery aneurysm and diffuse aneurysmatic disease involving most intra-abdominal organs, suggestive of polyarteritis nodosa. Although treatment with high-dose steroids was initiated, the patient died of progressive bowel ischaemia.

The effects of nitric oxide supplementation and inhibition on bacterial translocation in bile duct ligated rats.

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. L-arginine or N(G)-nitro-L-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The L-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.

Decrease of CD4+CD25+ T cells in peripheral blood after liver transplantation: association with immunosuppression.

CD25 (IL-2 receptor alpha-chain) marks a population of CD4-positive T cells with a suppressor phenotype. These CD4+CD25+ regulatory T cells can suppress both effector T cells and antigen-presenting cells and have been identified as a principle regulator of tolerance in experimental transplantation models. In the setting of human liver transplantation, however, little is known about the dynamics of these cells in relation to rejection, tolerance, and immunosuppression. In the current study we determined CD4+CD25+ T cell in blood of liver transplant recipients using flow cytometry and investigated a possible link with immunosuppressive therapies. Peripheral blood mononuclear cells (PBMC) of 27 liver transplant patients (pretransplantation and 12 months posttransplantation) and 16 healthy controls were included. We found that the percentages of CD25+ cells within the CD4 T-cell population was significantly reduced in more than two-thirds of patients 1 year after transplantation. Also the total percentage of CD4-positive T cells declined significantly within this period, making the absolute reduction of regulatory T cells after transplantation even more profound. Comparing PBMC samples of patients and healthy controls revealed an increased percentage of CD4+ T cells in the patients before transplantation, probably related to the chronic liver illness. The reduction in CD4+CD25+ T cells after transplantation was similar for different immunosuppression regiments. All patients, however, received calcineurin inhibitors, suggesting a possible suppressive effect of this therapy on regulatory T-cell levels in peripheral blood. Currently, assays for regulatory T-cell activity are used to further support this hypothesis.

Is synchronous bowel anastomosis safe?

In this study, we investigated the effects of synchronous anastomosis on intestinal healing in experimental colonic resection. Sprague-Dawley rats were randomized into 3 groups; control (group I), single anastomosis (group II) and synchronous (double) anastomosis (group III). Single and proximal anastomoses were located 3 cm distal to caecum, and distal anastomoses were done 3 cm distal to them. On the 7th postoperative day, bursting pressure, hydroxyproline level and histology of the anastomotic site were assessed. Bursting pressures and hydroxyproline levels indicated that impaired healing of proximal anastomoses in group III was evident. Proximal anastomoses in group III had the lowest hydroxyproline value and bursting pressure level. Significant fibrosis was observed in the histological examination of distal anastomoses in group III. Double colonic anastomoses is not as safe as single anastomoses and involves additional risk. The healing of proximal anastomosis is significantly altered after experimental synchronous resection.

Effect of abdominal insufflation on bacterial growth in experimental peritonitis.

BACKGROUND: Perforated appendicitis can be treated laparoscopically, but this approach is associated with a higher rate of intra-abdominal abscess. Pneumoperitoneum impairs the clearance of bacteria from the peritoneal cavity in experimental models of peritonitis. The aim of this study was to investigate the effects of intra-abdominal gas insufflation on bacterial growth in a rat model. MATERIALS AND METHODS: The effects of intraperitoneal insufflation with different gases and a gasless model on bacterial proliferation in a setting of Escherichia coli-induced experimental peritonitis were studied in a rat model. Saline (0.25 mL) was given intraperitoneally to six Wistar male rats as the sham group. Escherichia coli (1.5 x 10(9) cfu/mL per kilogram) was injected intraperitoneally into to 24 rats. Microorganism counts were taken after 8 hours, and rats were divided into three groups: group 1, CO2 insufflation; group 2, N2O insufflation; and group 3, no insufflation. Microorganism counts were repeated 8 hours after the procedure (at 16 hours postinjection). RESULTS: The difference in microorganism counts between 8 and 16 hours were significant in the CO2 and N2O insufflation groups (P < 0.05) but not in the group without pneumoperitoneum. CONCLUSIONS: Abdominal insufflation may promote intra-abdominal bacterial growth or decrease intra-abdominal bacterial clearance.