Hard Block Degradable Polycarbonate Urethanes: Promising Biomaterials for Electrospun Vascular Prostheses.

We report biodegradable thermoplastic polyurethanes for soft tissue engineering applications, where frequently used carboxylic acid ester degradation motifs were substituted with carbonate moieties to achieve superior degradation properties. While the use of carbonates in soft blocks has been reported, their use in hard blocks of thermoplastic polyurethanes is unprecedented. Soft blocks consist of poly(hexamethylene carbonate), and hard blocks combine hexamethylene diisocyanate with the newly synthesized cleavable carbonate chain extender bis(3-hydroxypropylene)carbonate (BHPC), mimicking the motif of poly(trimethylene carbonate) with highly regarded degradation properties. Simultaneously, the mechanical benefits of segmented polyurethanes are exploited. A lower hard block concentration in BHPC-based polymers was more suitable for vascular grafts. Nonacidic degradation products and hard block dependent degradation rates were found. Implantation of BHPC-based electrospun degradable vascular prostheses in a small animal model revealed high patency rates and no signs of aneurysm formations. Specific vascular graft remodeling and only minimal signs of inflammatory reactions were observed.

Long Term Evaluation of Nanofibrous, Bioabsorbable Polycarbonate Urethane Grafts for Small Diameter Vessel Replacement in Rodents.

OBJECTIVE: Biodegradable materials for in situ vascular tissue engineering could meet the increasing clinical demand for sufficient synthetic small diameter vascular substitutes in aortocoronary bypass and peripheral vascular surgery. The aim of this study was to design a new degradable thermoplastic polycarbonate urethane (dPCU) with improved biocompatibility and optimal biomechanical properties. Electrospun conduits made from dPCU were evaluated in short and long term follow up and compared with expanded polytetrafluoroethylene (ePTFE) controls. METHODS: Both conduits were investigated prior to implantation to assess their biocompatibility and inflammatory potential via real time polymerase chain reaction using a macrophage culture. dPCU grafts (n = 28) and ePTFE controls (n = 28) were then implanted into the infrarenal abdominal aorta of Sprague-Dawley rats. After seven days, one, six, and 12 months, grafts were analysed by histology and immunohistochemistry (IHC) and assessed biomechanically. RESULTS: Anti-inflammatory signalling was upregulated in dPCU conduits and increased significantly over time in vitro. dPCU and ePTFE grafts offered excellent long and short term patency rates (92.9% in both groups at 12 months) in the rat model without dilatation or aneurysm formation. In comparison to ePTFE, dPCU grafts showed transmural ingrowth of vascular specific cells resulting in a structured neovessel formation around the graft. The graft material was slowly reduced, while the compliance of the neovessel increased over time. CONCLUSION: The newly designed dPCU grafts have the potential to be safely applied for in situ vascular tissue engineering applications. The degradable substitutes showed good in vivo performance and revealed desirable characteristics such as biomechanical stability, non-thrombogenicity, and minimal inflammatory response after long term implantation.

Preserved right ventricular integrity in a new telemetric rat model of severe pulmonary hypertension.

Telemetric monitoring of hemodynamic parameters has become an established standard in experimental models of pulmonary arterial hypertension (PAH). To that purpose, a dedicated catheter is usually implanted through the right ventricular wall of study animals. Drawbacks of this standard technique are as follows: obtained pressures are from the right ventricle and therefore only surrogates for pulmonary arterial pressures, and furthermore, right ventricular myocardium is always damaged to a certain degree. To overcome shortcomings of standard hemodynamic assessment, we modified an established rat model, where severe PAH is induced by left-sided pneumonectomy plus monocrotaline injection. We describe here a novel telemetry catheter implantation technique, where the device is advanced into the pulmonary artery via the remaining stump and the transmitter is placed in a subcutaneous pocket. A total of 105 rats were operated with a median (range) implantation time of 50 (30-88) min and an excellent perioperative survival of 93%. After monocrotaline induction on day 7, animals developed severe PAH with mean ± SD pressures of 75.9 ± 18.6 (systolic), 55.0 ± 18.0 (mean), and 42.1 ± 21.3 mmHg (diastolic) after 4 wk. Postmortem, the animals showed severe right ventricular hypertrophy, and histological analysis confirmed excessive medial hypertrophy and intimal hyperplasia, both characteristic features of human PAH. Comparison of the new telemetric model with standard microtip catheterization did not show relevant measurement differences. We established the first experimental animal model for PAH with preserved right ventricular integrity that allows direct telemetric monitoring of real-time systolic, mean, and diastolic pressures in the main pulmonary artery of freely moving rats.

Mass spectrometric imaging of in vivo protein and lipid adsorption on biodegradable vascular replacement systems.

Cardiovascular diseases present amongst the highest mortality risks in Western civilization and are frequently caused by arteriosclerotic vessel failure. Coronary artery and peripheral vessel reconstruction necessitates the use of small diameter systems that are mechanically stress-resistant and biocompatible. Expanded polytetrafluorethylene (ePTFE) is amongst the materials used most frequently for non-degradable and bio-degradable vessel reconstruction procedures, with thermoplastic polyurethanes (TPU) representing a promising substitute. The present study describes and compares the biological adsorption and diffusion occurring with both materials following implantation in rat models. Gel electrophoresis and thin-layer chromatography, combined with mass spectrometry and mass spectrometry imaging, were utilized to identify the adsorbed lipids and proteins. The results were compared with the analytes present in native aorta tissue. It was revealed that both polymers were severely affected by biological adsorption after 10 min in vivo. Proteins associated with cell growth and migration were identified, especially on the luminal graft surface, while lipids were found to be located on both the luminal and abluminal surfaces. Lipid adsorption and cholesterol diffusion were found to be correlated with the polymer modifications identified on degradable thermoplastic urethane graft samples, with the latter revealing extensive cholesterol adsorption. The present study demonstrates an interaction between biological matter and both graft materials, and provides insights into polymer changes, in particular, those observed with thermoplastic urethanes already after 10 min in vivo exposure. ePTFE demonstrated minor polymer modifications, whereas several different polymer signals were observed for TPU, all were co-localized with biological signals.

Accuracy of non-invasive liver stiffness measurement and steatosis quantification in patients with severe and morbid obesity.

BACKGROUND: Vibration controlled transient elastography (VCTE) and controlled attenuation parameter (CAP™) have shown reliable performance predicting fibrosis and steatosis in normal- to overweight patients but have not been validated in severe to morbid obesity. This study aimed at determining the accuracy of VCTE, CAP™ and the composite score FibroScan-AST (FAST) in patients with a body mass index (BMI) of ≥35 kg/m2. METHODS: Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™ measurement, and intraoperative liver biopsy. The feasibility and accuracy of VCTE, CAP™ and the composite score FAST were retrospectively analysed to evaluate fibrosis, steatosis and active fibrotic non-alcoholic steatohepatitis [NASH + non-alcoholic fatty liver disease (NAFLD) activity score ≥4 + fibrosis grade ≥2] using per protocol (PP) and intent to diagnose (ITD) calculation. RESULTS: In total, 170 patients (median BMI 44.4 kg/m2) were included in the study. Liver biopsy showed NASH, simple steatosis, and normal livers in 60.6% (n=103), 28.8% (n=49), and 10.6% (n=18), respectively. VCTE and CAP™ delivered reliable results in 90.6% (n=154/170) and 90.5% (n=134/148). The AUC (PP) of VCTE, CAP™, and FAST were 0.687 (≥F2), 0.786 (≥F3), 0.703 (≥S2), 0.738 (S3), and 0.780 (active fibrotic NASH). The AUC increased to 0.742 (≥F2), 0.842 (≥F3), 0.712 (≥S2), 0.780 (S3), and 0.836 (active fibrotic NASH) in patients below the median BMI of 44.4 kg/m2. CONCLUSIONS: VCTE, CAP™ and FAST show acceptable accuracy for the detection of fibrosis, steatosis and NASH in a real-life cohort of patients with obesity. Accuracy improves in patients with a BMI <44.4 kg/m2.

Impact of limb length on nutritional status in one-anastomosis gastric bypass: 3-year results.

BACKGROUND: Bariatric metabolic surgery is a well-established treatment option associated with significant weight loss and an improvement of metabolic co-morbidities. However, the changes in gastrointestinal anatomy frequently result in nutritional deficiencies. OBJECTIVE: To evaluate the impact of biliopancreatic limb length in one-anastomosis gastric bypass (OAGB) on micronutrient and protein deficiencies. SETTING: University hospital, Austria. METHODS: All patients that were (1) undergoing OAGB between 2012 and 2014, and (2) had at least 3 postoperative follow-up visits were retrospectively analyzed. Systemic levels of parathyroid hormone, vitamins (A, D, E, and B12), folic acid, magnesium, calcium, iron, albumin, and ferritin were correlated to biliopancreatic limb length as follows: short limb (150 cm), intermediate limb (200 cm), and long limb (250 cm). RESULTS: A total of 155 patients fulfilled inclusion criteria (female/male: n = 111/44). OAGB led to a mean percent excess weight loss of 79.9 (±24.2) and a reduction of mean body mass index from 45.4 kg/m2 (±6.1 kg/m2) at baseline to 30.2 kg/m2 (±9.9 kg/m2). Preoperative deficiencies were seen in 25-hydroxy-vitamin D (93.8%), folic acid (27.6%), ferritin (4.1%), vitamin A (5.5%), and vitamin B12 (2.3%). In patients with long limb, systemic folic acid levels were significantly lower after 24 months postoperatively compared with short and intermediate limb (P < .05). No difference was observed for vitamin D, A, E, B12, and iron and no patient suffered from severe protein malnutrition. CONCLUSION: Nutritional deficiencies were common after OAGB without severe deficiencies in biliopancreatic limb lengths ranging from 150 to 250 cm. A trend can be observed with more pronounced deficiencies with intermediate and long limb lengths without significant differences for most micronutrients.

Stapling Through a Bougie During Sleeve Gastrectomy in a Superobese Patient-a Video Vignette.

PURPOSE: Bariatric-metabolic surgery in superobese patients (BMI > 50 kg/m2) is very challenging indeed with little room for error. In many cases, a two-step procedure is required, since more complex primary bariatric procedures can be technically demanding and bearing a relevant risk for the patient. At our institution, laparoscopic sleeve gastrectomy (SG) is the preferred primary procedure, followed by a conversion to either SADI-S or Roux-en-Y gastric bypass (RYGB) after initial weight loss is achieved [1, 2]. This video aims at demonstrating the conversion from primary SG to RYGB due to an adverse event in a 45-year-old superobese female patient (weight, 170 kg; BMI, 73 kg/m2). METHODS: An intraoperative laparoscopic video has been anonymized and edited to demonstrate the course of the operation on the patient mentioned above. RESULTS: The start of the procedure was uneventful. After a successful mobilization of the greater curvature, the stomach was resected with an electronic stapling device guided by a firm 36-french bougie (Rüsch, Germany) towards the angle of His. Due to a limited view, a stapler was placed over the bougie, which resulted in the stomach being subtotally transected, the staples attaching the bougie to the sleeve about 5 cm from the gastroesophageal junction. Salvage surgery after removing the remnants of the bougie was a conversion to RYGB. CONCLUSION: When performing a bariatric-metabolic surgery in superobese patients, an extended skill level is required to provide a solution, should anything go wrong. Therefore, we suggest bariatric-metabolic surgery in superobese patients to be performed solely and specifically at high-volume centres.

Roux-en-Y Gastric Bypass as a Treatment for Barrett's Esophagus after Sleeve Gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is the most frequently performed bariatric procedure today. While an increasing number of long-term studies report the occurrence of Barrett's esophagus (BE) after SG, its treatment has not been studied, yet. OBJECTIVES: The aim of this study was to evaluate Roux-en-Y gastric bypass (RYGB) as treatment for BE and reflux after SG. SETTING: University hospital setting, Austria METHODS: This multi-center study includes all patients (n = 10) that were converted to RYGB due to BE after SG in Austria. The mean interval between SG and RYGB was 42.7 months. The follow-up after RYGB in this study was 33.4 months. Gastroscopy, 24 h pH-metry, and manometry were performed and patients were asked to complete the BAROS and GIQLI questionnaires. RESULTS: Weight and BMI at the time of SG was 120.8 kg and 45.1 kg/m2. Eight patients (80.0%) went into remission of BE after the conversion to RYGB. Two patients had RYGB combined with hiatoplasty. The mean acid exposure time in 24 h decreased from 36.8 to 3.8% and the mean DeMeester score from 110.0 to 16.3. Patients scored 5.1 on average in the BAROS after conversion from SG to RYGB which denotes a very good outcome. CONCLUSIONS: RYGB is an effective therapy for patients with BE and reflux after SG. Its outcomes in the current study were BE remission in the majority of cases as well as a decrease in reflux activity. Further studies with larger cohorts are necessary to confirm these findings.

Surgical therapy of weight regain after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a well-established surgical method for morbid obesity; however, weight regain (WR) after initially good results may be considered an issue, the treatment of which has found no consensus yet. OBJECTIVES: The aim of this study was to compare the different surgical methods treating WR after RYGB that are used at the Vienna Medical University in a larger number of patients, concerning further weight loss, complications, and reoperations. SETTING: University hospital, Austria. METHODS: This study includes all patients with RYGB who were reoperated due to WR at the Vienna Medical University by December 2016 (n = 84). The follow-up rate was 93%. The following 4 approaches to treating WR after RYGB were taken: (1) pouch resizing, (2) pouch banding, (3) pouch resizing plus pouch banding, and (4) common limb shortening (i.e., distalization). RESULTS: The mean maximum excess weight loss referring to the WR procedure in the 4 groups was as follows: group 1: 69.0% ± 35.2%, group 2: 62.8% ± 39.5%, group 3: 83.1% ± 30.9%, and group 4: 81.5% ± 41.6%. Reoperations occurred in the following different groups: group 1 had 2 balloon dilations (20%), groups 2 (n = 13) and 3 (n = 29) had 5 (38% and 17%) band removals each, and group 4 had 9 reversal procedures due to malnutrition (30%). CONCLUSIONS: There are nonsignificant differences in terms of additional weight loss between the different methods. However, differences lay in the areas of adverse symptoms and further reoperations. While there was no risk of malnutrition with pouch resizing, there was with distalization. Pouch banding (with or without resizing) poses a higher risk of dysphagia.

Evaluation and comparison of six noninvasive tests for prediction of significant or advanced fibrosis in nonalcoholic fatty liver disease.

Background: In nonalcoholic fatty liver disease (NAFLD), advanced fibrosis has been identified as an important prognostic factor with increased liver-related mortality and treatment need. Due to the high prevalence of NAFLD, noninvasive risk stratification is needed to select patients for liver biopsy and treatment. Objective: To compare the diagnostic accuracy of several widely available noninvasive tests for assessment of fibrosis among patients with NAFLD with or without nonalcoholic steatohepatitis (NASH). Methods: We enrolled consecutive patients with NAFLD admitted to two Austrian referral centers who underwent liver biopsy. Liver stiffness measurement (LSM) was obtained by vibration-controlled transient elastography (VCTE, FibroScan) and blood samples were collected for determination of enhanced liver fibrosis (ELF) test, FibroMeterV2G, FibroMeterV3G, NAFLD fibrosis score (NFS), and fibrosis-4 index (FIB-4). Results: Our study cohort contained 186 patients with histologically confirmed NAFLD. On liver histology, NASH was present in 92 patients (50%), significant fibrosis (F ≥ 2) in 71 patients (38%), advanced fibrosis (F ≥ 3) in 49 patients (26%), and F ≥ 3 plus NASH in 35 patients (19%). For diagnosis of F ≥ 2, F ≥ 3, and F ≥ 3 plus NASH, respectively, receiver operating characteristic (ROC) analysis revealed superior diagnostic accuracy of ELF score (area under ROC curve (AUROC) 0.85, 0.90, 0.90), FibroMeterV2G (AUROC 0.86, 0.88, 0.89), FibroMeterV3G (AUROC 0.84, 0.88, 0.88), and LSM per protocol (AUROC 0.87, 0.95, 0.91) versus FIB-4 (AUROC 0.80, 0.82, 0.81) or NFS (AUROC 0.78, 0.80, 0.79). Conclusion: Proprietary fibrosis panels and VCTE show superior diagnostic accuracy for noninvasive diagnosis of fibrosis stage in NAFLD as compared to FIB-4 and NFS.

Quality of Life 10 Years after Sleeve Gastrectomy: A Multicenter Study.

OBJECTIVE: Sleeve gastrectomy (SG) has recently become the most commonly applied bariatric procedure worldwide. Substantial regaining of weight or severe reflux might compromise quality of life (QOL) after SG in the long-term follow-up. Long-term data on patients' QOL is limited, even though the persistent improvement in QOL is one of the aims of bariatric surgery. The objective of this study was to present patients' QOL 10 years after SG. METHODS: Of 65 SG patients with a follow-up of ≥10 years after SG who were asked to fill out the Bariatric Quality of Life Index (BQL) and Short Form 36 (SF36) questionnaires, 48 (74%) completed them. This multicenter study was performed in a university hospital setting in Austria. RESULTS: The BQL score revealed nonsignificant differences between the patients with > 50% or < 50% excess weight loss (EWL). It did show significant differences between patients with and without any symptoms of reflux. Patients with < 50% EWL scored significantly lower in 3/8 categories of SF36. Patients suffering from reflux had significantly lower scores in all categories. CONCLUSIONS: EWL and symptomatic reflux impair patients' long-term QOL after SG.

Significant Liver-Related Morbidity After Bariatric Surgery and Its Reversal-a Case Series.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) occurs in up to 80% of patients with obesity. Current data suggest an improvement of NAFLD after established bariatric procedures. OBJECTIVES: This study investigated liver function impairment after Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB). SETTING: University Hospital, Bariatric Surgery Unit METHODS: In this single-center case series, consecutive in- and outpatients after bariatric surgery who presented with severe liver dysfunction from March 2014 to February 2017 were included and followed until March 2017. RESULTS: In total, 10 patients (m:f = 2:8; median age 48 years, range 22-66 years) were included. Liver dysfunction occurred after a median postoperative time of 15 months (range 2-88 months). Median %excess weight loss at that time was 110.6% (range 85.2-155.5%). Liver steatosis/fibrosis occurred in 70%, cirrhosis in 30% of patients, and led to fatigue (90%), ascites (70%), hepatic encephalopathy (30%), and upper gastrointestinal bleeding (20%). Elevation of transaminases, impairment of coagulation parameters, thrombocytopenia, and hypoalbuminemia were present in 70, 80, 70, and 100%, respectively. In eight patients, lengthening of the alimentary/common limb led to an improvement or complete remission of symptoms. In one patient, liver transplantation was required, one patient deceased due to septic shock and decompensated liver disease. CONCLUSIONS: Severe liver dysfunction may also occur after bariatric procedures such as OAGB and RYGB. A comprehensive, meticulous follow-up for early identification of postoperative liver impairment should be aspired. Bypass length reduction led to a fast improvement in all patients.

Update: 10 Years of Sleeve Gastrectomy-the First 103 Patients.

BACKGROUND: Sleeve gastrectomy (SG) has been the most frequently performed bariatric procedure worldwide since 2014. Therefore, it is vital to look at its outcomes in a long-term follow-up based on a large patient collective. Main points of discussion are weight regain, reflux, and patients' quality of life at 10+ years after the procedure. OBJECTIVES: The aim of this study is to present an update of data that have been published recently and, thus, achieve more conclusive results. The number of patients has been doubled, and the length of the follow-up is still 10+ years. SETTING: Multi-center study, medical university clinic, Austria METHODS: This study includes all patients who had SG before December 2006 at the participating bariatric centers. At 10+ years, non-converted patients (67%) were examined using gastroscopy, manometry, 24-hour pH-metry, and questionnaires. Patients' history of weight, comorbidities, and reflux were established through interviews. RESULTS: At 10+ years after SG, the authors found a conversion rate of 33%, an %EWL in non-converted patients of 50.0 ± 22.5, reflux in 57%, and Barrett's metaplasia in 14% of non-converted patients. Gastroscopies revealed that patients with reflux were significantly more likely to have de-novo hiatal hernia. A significantly lower quality of life was detected through GIQLI and BAROS in patients with reflux. CONCLUSION: The authors recommend gastroscopies at 5-year intervals after SG to detect the possible sequelae of reflux at an early stage. Conversion to Roux-en-Y-gastric bypass (RYGB) works well to cure patients from reflux but may not be as efficient at treating weight regain.

Biocompatibility Assessment of a New Biodegradable Vascular Graft via In Vitro Co-culture Approaches and In Vivo Model.

Following the implantation of biodegradable vascular grafts, macrophages and fibroblasts are the major two cell types recruited to the host-biomaterial interface. In-vitro biocompatibility assessment usually involves one cell type, predominantly macrophages. In this study, macrophage and fibroblast mono- and co-cultures, in paracrine and juxtacrine settings, were used to evaluate a new biodegradable thermoplastic polyurethane (TPU) vascular graft. Expanded-polytetrafluoroethylene (ePTFE) grafts served as controls. Pro/anti-inflammatory gene expression of macrophages and cytokines was assessed in vitro and compared to those of an in vivo rat model. Host cell infiltration and the type of proliferated cells was further studied in vivo. TPU grafts revealed superior support in cell attachment, infiltration and proliferation compared with ePTFE grafts. Expression of pro-inflammatory TNF-α/IL-1α cytokines was significantly higher in ePTFE, whereas the level of IL-10 was higher in TPU. Initial high expression of pro-inflammatory CCR7 macrophages was noted in TPU, however there was a clear transition from CCR7 to anti-inflammatory CD163 expression in vitro and in vivo only in TPU, confirming superior cell-biomaterial response. The co-culture models, especially the paracrine model, revealed higher fidelity to the immunomodulatory/biocompatibility behavior of degradable TPU grafts in vivo. This study established an exciting approach developing a co-culture model as a tool for biocompatibility evaluation of degradable biomaterials.