Early Leakage Research Articles

Application of an Array of Metal-Oxide Semiconductor Gas Sensors in an Assistant Personal Robot for Early Gas Leak Detection

This paper proposes the application of a low-cost gas sensor array in an assistant personal robot (APR) in order to extend the capabilities of the mobile robot as an early gas leak detector for safety purposes. The gas sensor array is composed of 16 low-cost metal-oxide (MOX) gas sensors, which are continuously in operation. The mobile robot was modified to keep the gas sensor array always switched on, even in the case of battery recharge. The gas sensor array provides 16 individual gas measurements and one output that is a cumulative summary of all measurements, used as an overall indicator of a gas concentration change. The results of preliminary experiments were used to train a partial least squares discriminant analysis (PLS-DA) classifier with air, ethanol, and acetone as output classes. Then, the mobile robot gas leak detection capabilities were experimentally evaluated in a public facility, by forcing the evaporation of (1) ethanol, (2) acetone, and (3) ethanol and acetone at different locations. The positive results obtained in different operation conditions over the course of one month confirmed the early detection capabilities of the proposed mobile system. For example, the APR was able to detect a gas leak produced inside a closed room from the external corridor due to small leakages under the door induced by the forced ventilation system of the building.

Application of Piezosurgery in En Bloc Laminectomy for the Treatment of Multilevel Thoracic Ossification of Ligamentum Flavum

To evaluate safety and effectiveness of the application of piezosurgery in en bloc laminectomy for the treatment of multilevel thoracic ossification of ligamentum flavum (MTOLF). Forty-one cases who had MTOLF and underwent en bloc laminectomy from January 2012 to January 2017 were reviewed and divided into Group A (high-speed drill, n= 23) and Group B (piezosurgery, n=18). Comparisons in clinical outcome and perioperative complications were carried out between the 2 groups. Mean follow-up period was comparable between Group A (12.6 months) and Group B (11.4 months). Both operation time and intraoperative blood loss in Group A were significantly more than those in Group B (P < 0). Although final Japanese Orthopaedic Association (JOA) score in both groups significantly increased, differences in preoperative JOA, final JOA, and neurologic recovery rate between the 2 groups weren't significant. Perioperative complications included early neurologic deterioration (1 in Group A), wound infection (2 in Group A and 1 in Group B), and leakage of cerebrospinal fluid (5 in Group A and 1 in Group B); incidences of these complications between the 2 groups weren't significant (P > 0.05). A relationship analysis showed that cases with preoperative tram track sign, tuberous OLF, or larger compression ratio were at greater risk of developing an intraoperative dura defect. The application of piezosurgery in en bloc laminectomy is a safe and effective method in the treatment of MTOLF, and it was advantageous for reducing both operation time and intraoperative blood loss compared with the high-speed drill.

Early drain removal after hepatectomy: an underutilized management strategy

Background: Randomized controlled trials and a Cochrane Review suggest that routine drainage is not necessary in patients undergoing hepatectomy. Contemporary ACS-NSQIP data suggest that 50% of patients undergoing hepatectomy in North America receive abdominal drains, and early drain removal is not widely practiced. Recent single center analyses from Japan demonstrates that drain removal by POD 2 or 3 is safe and may result in fewer organ space infections as well as shorter length of stay. Thus, the aim of this analysis is to compare the outcomes of North American patients who have early (POD 0-3) versus routine (POD 4-7) drain removal. Methods: Patients undergoing major hepatectomy (≥ 3 segments) or partial hepatectomy (≤ 2 segments) were identified in the 2014–16 ACS-NSQIP Procedure Targeted Participant Use File. Patients undergoing concomitant biliary reconstruction or colon resection were excluded. Only patients who had one or more drains placed at surgery were analyzed. Patients who had drains in place for more than 7 days also were excluded so that early drain removal (POD 0-3) could be compared to routine drain removal (POD 4-7) in patients without early bile leaks or other complications. Patients were stratified by extent of hepatectomy and propensity score matched for multiple demographic, comorbidity, laboratory, procedure and pathologic variables. Outcomes of early and routine drain removal patients were compared by Mann-Whiting U and chi-square test. Results: Of 2,599 patients, 1,654 (64%) underwent a partial (PH) and 945 (36%) had a major hepatectomy (MH). Early drain removal was performed in 661 (40%) of PH and 211 (22%) of MH patients. Multiple outcomes were significantly (p < 0.01) better in the early drain removal patients, but these patients were less likely (p < 0.01) to have hepatitis, a prior biliary stent, neoadjuvant therapy, a major hepatectomy, a Pringle maneuver, a concurrent ablation, perioperative transfusions, or malignant pathology. Therefore, 779 early drain removal patients were matched to 779 routine drain removal patients (Table). Early drain removal patients had significantly less (p < 0.02) overall and serious morbidity, fewer pneumonias and required fewer postoperative biliary drainage procedures. Length of stay was 2 days shorter, (p<0.001) and readmissions were 3% lower (p < .01) in early drain removal patients. Conclusion: Early drain removal (POD 0-3) is performed in only one-third of hepatectomy patients who receive drains. Routine drain removal (POD 4-7) is practiced in a variety of patients some of whom are perceived to be at higher risk for complications. After controlling for these factors, early drain removal is associated with lower overall and serious morbidity as well as shorter length of stay and fewer readmissions. Early drain removal after hepatecomy is an underutilized management strategy.

Probabilistic evaluation of above-zone pressure and geochemical monitoring for leakage detection at geological carbon sequestration site

Above-zone monitoring has been proposed as a promising technique for monitoring geological carbon sequestration (GCS) projects for storage integrity. This study presents a probabilistic framework to assess and compare effectiveness of above-zone monitoring of pressure and geochemical parameters for the pilot GCS project at the Cranfield site. Pressure responses in the above-zone monitoring interval (AZMI) to leaks were modeled with a single-phase flow equation and solved analytically and geochemical responses were modeled with a solute transport equation coupled with geochemical reactions, such as mineral dissolution, aqueous complexation, cation exchange, caused by intrusion of the leaked fluids having lower pH and solved semi-analytically. A total of one million realizations were generated using the Monte-Carlo method in terms of 11 parameters required to calculate pressure and geochemical responses to leaks in the AZMI. For each individual realization, time to detect leaks in the AZMI was estimated with pressure with threshold values 200 MPa, 2000 MPa, and 10000 MPa or geochemical parameter (dissolved CO2 in groundwater) with threshold values of 2.33 mmol/kg H2O, 2.82 mmol/kg H2O, 6.94 mmol/kg H2O as indicator and further analyzed statistically over the one million realizations. Our results show that pressure monitoring can detect more than 90% of the leaks whereas geochemical monitoring can detect only up to 50% of the leaks. Detection time ranges from several hours to 200 days for pressure monitoring and from 1 year to 30 years for geochemical monitoring, suggesting that pressure monitoring can provide much early leakage detection. The local relative and global sensitivity analyses were conducted to rank relative importance of the model parameters. Our results show that detection time is sensitive to distance of monitoring well, leakage rate, thickness of the AZMI, and permeability. The global sensitivity analysis shows that the total indices are much higher than the first-order indices, indicating that interactions among the model parameters are crucial to detection time. The probabilistic framework presented in this study can be easily applied to the site configurations of other commercial-scale GCS projects.

Early Experience with Intraoperative Leak Test Using a Blend of Methylene Blue and Indocyanine Green During Robotic Gastric Bypass Surgery.

Leak tests using air or methylene blue (MB) for gastrojejunal anastomoses are often performed during gastric bypass surgeries to avoid leaks due to technical errors. Still, early leaks have been reported in the literature. Indocyanine green (ICG) fluorescence with laser excitement makes this dye easily visible even in small amounts, and, thus, may be an excellent agent for leak testing. During robotic gastric bypass surgery, a leak test of a gastrojejunal anastomosis was performed with air through a nasogastric tube under manual occlusion of the jejunum. Afterward, 50ml of a mix of 100ml sterile water, 2mg of MB, and 5mg ICG was injected through the same tube. The entire anastomosis was inspected for integrity under both fluorescent and normal light modes. Leak tests with air and the blend of MB and ICG have been performed in 95 patients from January 2017 to April 2018. No intraoperative leak test-related adverse events occurred. Zero (0%) patients had a positive leak test with air, 0 patients showed MB excretion, and an ICG leak was observed in four (4.2%) patients. No anastomotic complications, including leaks and/or strictures, were found 30days postoperatively. Leak tests using a blend of MB and ICG appear to be more sensitive for small defect detection of gastrojejunal anastomoses during robotic gastric bypass surgery. Larger datasets and research that is more stringent are needed to determine the exact clinical value of this new method.

Practical approach to urine leak after kidney transplant

Urological complications can cause significant morbidity after kidney transplant but can be prevented by following well-known good surgical principles and techniques. The key is early identification and appropriate intervention. This article discusses clinical presentation, investigations, and principles of management of a urine leak after kidney transplant on the background of a clinical case. The presence of a ureteric catheter, double J ureteric anastomotic stent, vascularity of transplanted ureter, and bladder capacity is critical for differential diagnosis, choice of investigation, and management of ureteral leak. The given case demonstrates an early extraperitoneal high-volume urinary leak. Additional information about the surgery, graft quality, and postoperative clinical course may help in differential diagnosis. Drain fluid creatinine and potassium analysis compared with serum can confirm the leak, whereas radiological imaging can localize it. Depending on the cause and site of leak identified, a conservative management approach using maximal decompression or surgical repair or reconstruction may be appropriate.

Efficacy of the cardiac septal occluder in the treatment of post-bariatric surgery leaks and fistulas

Endoscopy has evolved to become first-line therapy for the treatment of post-bariatric leaks; however, many sessions are often required with variable success rates. Due to these limitations, the use of the cardiac septal defect occluder (CSDO) has recently been reported in this population. The study population was a multicenter retrospective series of patients with post-bariatric surgical leaks who underwent treatment with CSDO placement. Data on the type of surgery, previous treatment details, fistula dimensions, success rate, and adverse events were collected. Leaks were grouped according to the International Sleeve Gastrectomy Expert Panel Consensus. Outcomes included technical and clinical success and safety of the CSDO. Regression analysis was performed to determine the predictors of response. Forty-three patients with leaks were included (31 sleeve gastrectomy and 12 Roux-en-Y gastric bypass). They were divided into acute (n= 3), early (n= 5), late (n= 23), and chronic (n= 12). Forty patients had failed previous endoscopic treatment and 3 patients had CSDO as the primary treatment. Median follow-up was 34 weeks. Technical success was achieved in all patients and clinical success in 39 patients (90.7%). All chronic, late, and early leaks were successfully closed, except one undrained late leak. The 5 patients with early leaks had an initial satisfactory response, but within 30 days, drainage recurred. The CSDOs were removed and replaced with larger-diameter devices leading to permanent defect closure. Acute leaks were not successfully closed in all 3 patients. Regression analysis showed that chronicity and previous treatment were associated with fistula closure; success rates for late/chronic leaks versus acute/early leaks were 97.1% and 62.5%, respectively (P= .0023). This observational study found that the CSDO had a high efficacy rate in patients with non-acute leaks, with no adverse events. All early, late, and chronic leaks were successfully closed, except for one undrained late leak. However, early leaks required a second placement of a larger CSDO in all cases. These results suggest that the CSDO should be considered for non-acute fistula and that traditional closure methods are likely preferred in the acute and early settings.

Study of Tribological analysis of PTFE and its filler using Taguchi Approach

Polytetrafluroethylene (PTFE) is self-lubricating tough, waxy, non-flammable synthetic resin produced by the polymerization of tetrafluroethylene. Pure PTFE is widely used as bearing material and many such applications which is subjected to high wear rate, can be reduced by adding suitable fillers. PTFE exhibits poor wear and abrasion resistance, leading to early failure and leakage problem in the machine parts. This paper present the experiment l analysis of three composites (PTFE + 35% Carbon, PTFE + 35% Glass, PTFE + 35% Bronze) showing how properties of PTFE can be improved by the addition of filler content. The effects of varying load, sliding distance, sliding velocity and filler content on wear in PTFE are studied. The results of experiments are proved that the wear is strongly influenced by the composition of filler content.

Intraepithelial Lymphocytosis of the Resection Margin in the Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Background: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a disease involving the intestine and is often diagnosed in surgically resected specimens. The disease prognosis of MEITL is fatal because of rapid recurrence and leakage after excision. Recently, in microscopic finding of MEITL, intraepithelial lymphocytosis in mucosa that were grossly intact has been reported. In this study, we evaluated the intraepithelial lymphocytosis of the resection margin to determine the reason for the early recurrence or leakage in MEITL.Materials and Methods: We reviewed the medical records of all patients who were diagnosed with small intestine lymphoma from January 1995 to June 2018 at our medical center. We analyzed a tissue array from 8 patients diagnosed with MEITL. The expression of CD3, CD5, and CD8 were analyzed by immunohistochemistry.Results: A total of 8 cases of small intestine lymphoma were collected in this period. There were three men (37.5%) and five women (mean age 55 years). Two patients died without initiation of chemotherapy. Six patients received chemotherapy after resection of MEITL (4 patients received CHOP regimens, 2 patients received ProMACE-CyBOM regimens), but five patients died within 6 months (mean survival time 4.1 months, range 0.3-12.1 months). Only one patient survived for 5 years. On gross examination, the distance to the resection margin was 7.58 cm (3.8-14.0 cm) on average. Microscopic examination revealed intraepithelial lymphocytosis at least of one of the resected margins in all case. Immunohistochemical staining for CD3, CD5, and CD8 was performed on the resection margins. As a result, severe intraepithelial lymphocytosis accompanied by aberrant loss of CD5 was observed in 6 cases (75%).Conclusion: In the MEITL, an intraepithelial lymphocytosis accompanied by aberrant CD5 loss is frequently observed in the resection margin, even if the resection margin is grossly intact, and there is no clear microscopic involvement of the lymphoma especially on low power. This fact is thought to be related to the early recurrence or leakage of MEITL at the surgical site. DisclosuresNo relevant conflicts of interest to declare.

Different Risk Factors for Early and Late Colorectal Anastomotic Leakage in a Nationwide Audit.

Anastomotic leakage remains a major complication after surgery for colorectal carcinoma, but its origin is still unknown. Our hypothesis was that early anastomotic leakage is mostly related to technical failure of the anastomosis, and that late anastomotic leakage is mostly related to healing deficiencies. The aim of this study was to assess differences in risk factors for early and late anastomotic leakage. This was a retrospective cohort study. The Dutch ColoRectal Audit is a nationwide project that collects information on all Dutch patients undergoing surgery for colorectal cancer. All patients undergoing surgical resection for colorectal cancer in the Netherlands between 2011 and 2015 were included. Late anastomotic leakage was defined as anastomotic leakage leading to reintervention later than 6 days postoperatively. In total, 36,929 patients were included; early anastomotic leakage occurred in 863 (2.3%) patients, and late anastomotic leakage occurred in 674 (1.8%) patients. From a multivariable multinomial logistic regression model, independent predictors of early anastomotic leakage relative to no anastomotic leakage and late anastomotic leakage relative to no anastomotic leakage included male sex (OR, 1.8; p < 0.001 and OR, 1.2; p = 0.013) and rectal cancer (OR, 2.1; p < 0.001 and OR, 1.6; p = 0.046). Additional independent predictors of early anastomotic leakage relative to no anastomotic leakage included BMI (OR, 1.1; p = 0.001), laparoscopy (OR, 1.2; p = 0.019), emergency surgery (OR, 1.8; p < 0.001), and no diverting ileostomy (OR, 0.3; p < 0.001). Independent predictors of late anastomotic leakage relative to no anastomotic leakage were Charlson Comorbidity Index of ≥II (OR, 1.3; p = 0.003), ASA score III to V (OR, 1.2; p = 0.030), preoperative tumor complications (OR, 1.1; p = 0.048), extensive additional resection because of tumor growth (OR, 1.7; p = 0.003), and preoperative radiation (OR, 2.0; p = 0.010). This was an observational cohort study. Most risk factors for early anastomotic leakage were surgery-related factors, representing surgical difficulty, which might lead to technical failure of the anastomosis. Most risk factors for late anastomotic leakage were patient-related factors, representing the frailty of patients and tissues, which might imply healing deficiencies. See Video Abstract at http://links.lww.com/DCR/A730.

RF07 AORTIC VALVE REPLACEMENT WITH SUTURELESS PERCEVAL BIOPROSTHESIS IN RIGHT ANTERIOR MINITHORACOTOMY APPROACH: SINGLE CENTER EXPERIENCE WITH 461 IMPLANTS

Abstract Background and Aim: Minimally invasive approach (MIA) reduces mortality and morbidity in patients referred for aortic valve replacement (AVR). Sutureless technology facilitates MIA. We describe our experience with sutureless Perceval (LivaNova, Italy) aortic bioprosthesis in right anterior minithoracotomy (RAMT) approach. Methods: Between March 2011 and December 2017, 841 patients underwent AVR with Perceval bioprosthesis. 461 patients were operated through RAMT approach. Considering only isolated AVR (530), Perceval in RAMT approach was performed in 87% of patients. Prosthesis sizes implanted were: S (n = 67), M (n = 147), L (n = 218) and XL (n = 29). Concomitant procedures were mitral valve surgery (n = 5), tricuspid valve repair (n = 1), mitral valve repair and tricuspid valve repair (n = 1), and miectomy (n = 2). Mean age was 77.2 ± 6.5, 61.12 % patients were female, and mean logistic EuroSCORE was 12.7 ± 9.9. Results: The 30-day mortality was 0.65% (3/461). Cardiopulmonary bypass and aortic cross-clamp times were 82.3 ± 30.8 and 52 ± 21.6 minutes for stand-alone procedures. In 3 patients appeared early moderate paravalvular leakage required reoperations. Permanent pacemaker implantation within the first 30 days was necessary in 5% of patients. At mean follow-up of 28.6 ± 12.4 months, survival was 97%, freedom from reoperation was 98%, and mean transvalvular pressure gradient was 11.7 ± 5 mmHg. Conclusions: AVR with Perceval bioprosthesis in RAMT approach is a safe and feasible procedure associated with low mortality and excellent hemodynamic performance. Sutureless technology facilitates RAMT approach.

Performing Reliable Early Leak Detection on Storage Tank Terminals: Retrofitting of Existing Facilities and New Buildings

Performing Reliable Early Leak Detection on Storage Tank Terminals: Retrofitting of Existing Facilities and New Buildings

Endoscopic vacuum therapy for a large esophageal perforation after bariatric stent placement.

Endoscopic vacuum therapy for a large esophageal perforation after bariatric stent placement.

PS02.209: PROGNOSTIC VALUE OF CHEST-TUBE AMYLASE IN DETECTING EARLY ANASTOMOTIC LEAKAGE AFTER IVOR-LEWIS ESOPHAGECTOMY

Abstract Background Intrathoracic anastomotic leaks after esophagectomy are a significant cause of postoperative morbidity and death. Early detection and timely management is crucial but existing diagnostic methods are either invasive or have a low sensitivity. The aim of this study was to evaluate the effectiveness of daily drain amylase levels in detecting early anastomotic leaks after Ivor-Lewis esophagectomy compared with C-Reactive Protein (CRP) levels. Methods Between June 2015 and September 2017, 126 Ivor-Lewis esophagectomies for cancer were performed in our surgical department. In 80 of these patients, drain amylase levels were collected as long a right-sided chest-tube was in place. Chest-tubes were removed at a secretion volume &lt; 300 ml/24 h. CRP levels were measured daily. If bile was detected in the chest-tube and/or after re-exploration of the chest, no further data were collected. Early anastomotic leaks were defined as occurring as long as the chest tubes were in site, in the mean the 5th postoperative day (POD). According to the collected data, drain amylase levels &gt; 350 U/l, and CRP &gt; 30 mg/dl were considered positive. Sensitivity and specificity in detecting anastomotic insufficiency for both drain amylase and CRP were calculated. Results A clinically significant anastomotic leak occurred in 7,1% (9/126) of all esophagectomy patients with 0,8% (1/126) postoperative 30-days mortality. An early anastomotic disruption occurred in 4 of the 80 analysed patients. Three of them had a positive chest-drain amylase level and none a positive CRP level on POD1. The same three patients had on POD 2 a positive CRP level or presented bile in the chest-tube. The fourth patient presented at POD 2 bile in the chest tubes. On POD 1 he presented neither positive amylase nor CRP. The sensitivity and specificity for drain amylase and CRP within the first 3 POD was 0,75 and 0,98 vs 0,75 and 0,85 respectively. The accuracy for both amylase and CRP were calculated at 0,97 vs 0,85. Conclusion Chest-tube amylase levels after Ivor-Lewis esophagectomy are more accurate for the detection of early esophageal anastomotic leaks than CRP. This could facilitate early detection of anastomotic leaks up to 24 hours earlier than elevated blood CRP levels. Disclosure All authors have declared no conflicts of interest.

ReGAE 12: preventing glaucoma blindness in the Caribbean through implementation of the Moorfields Safer Surgery System and skills transfer from the UK to Trinidad and Tobago.

ObjectiveThe objective of the study was to present evidence of successful skills transfer of the Moorfields Safer Surgery System (MSSS) from the UK to Trinidad and Tobago and the safety and efficacy of this technique.MethodsHospital-based retrospective, consecutive, non-comparative case series study of 33 eyes (24 African-Caribbean patients; 16 male patients) with primary open-angle glaucoma undergoing trabeculectomy + mitomycin C (MSSS) by a single surgeon with UK Glaucoma Fellowship training. The clinical outcome measures included intraocular pressure (IOP), bleb morphology, postsurgical interventions, postoperative complications, and best-corrected visual acuity (BCVA) at the final follow-up.ResultsAll patients were self-identified as African-Caribbean. The median age was 56 years (range 34–79 years). The mean preoperative IOP on maximum tolerated medical treatment was 22.4 mmHg (SD=5.9 mmHg). With or without medication, IOP was ≤21 mmHg in 92.6% at 1 year and 87.5% at 5 years. At 1 year, IOP was ≤18 mmHg in 78%, ≤15 mmHg in 73% and ≤14 mmHg in 52%. Removal of scleral flap releasable suture(s) was performed in 84%, 5-fluorouracil injection(s) in 88% and bleb needling revision in 38%. The most common complication was early transient bleb leak (52%). No patient developed endophthalmitis, hypotony maculopathy, suprachoroidal hemorrhage, or malignant glaucoma. At the final follow-up, 91% had excellent or satisfactory bleb morphology, and 73% had equal or better BCVA.ConclusionSkills transfer between different geographical and economic regions contributes to the prevention of avoidable blindness through disease control – one of the core strategies of the World Health Organization’s Vision 2020 initiative. In the Caribbean (Trinidad and Tobago), the MSSS was utilized by a surgeon with Glaucoma Fellowship training and achieved outcomes similar to best-published data. This success can be reproduced in other geographic locations.

Early bile duct leakage following orthotopic liver transplantation - too early for endoscopy?

Early bile duct leakage following orthotopic liver transplantation - too early for endoscopy?

Features of laparoscopic cholecystectomy in patients with chronic calculous cholecystitis and signs of ”non-functioning” gallbladder

Aim. To improve outcomes of laparoscopic cholecystectomy in patients with chronic cholecystitis and signs of “nonfunctioning” gallbladder via development of preventive, curative and diagnostic measures. Material and methods. Laparoscopic cholecystectomу was performed in 14 764 patients with chronic cholecystitis. Incidence and causes of intraoperative injury of extrahepatic bile ducts were retrospectively analyzed. Three basic forms of “non-functioning” gallbladder (hydropsy, sclerosis and atrophy, total filling by stones) were. Results. Biliary injury followed by bile leakage occurred in 38 (0.25%) cases. Intraoperative and early postoperative diagnosis was in 11 (28.9%) and 27 (71.1%) patients, respectively. Tangential trauma of common bile duct was found in 3 (7.8%) cases, complete intersection – in 8 (21%) patients. Herewith, 6 of them had sclerosis, 2 – total filling of gallbladder by stones. New diagnostic and curative approach was followed by only 2 (0.04%) cases of early postoperative bile leakage in 2010–2015. Injury of common bile duct was absent within the same period. Sclerosis and atrophy of gallbladder were diagnosed prior to surgery. Conclusion. There are 3 types of “non-functioning” gallbladder with risk of biliary trauma during laparoscopic cholecystectomy. Sclerosis and atrophy of gallbladder are predominantly followed by certain difficulties during laparoscopic cholecystectomy. New diagnostic and curative approach is useful to prevent iatrogenic biliary trauma.

Leakage Models for High-Level Power Estimation

Leakage currents are one major concern when designing recent CMOS devices, making design for leakage at all stages of the design process mandatory. Early leakage optimization requires early leakage prediction, and for electronic system level design, this means estimation capabilities at register transfer (RT) level or above. Existing models are very accurate, but slow [transistor level such as Berkeley Simulator (BSIM)], or the slightly faster gate level models (such as the Liberty library), disregard relevant parameters. We present RT level leakage macro models, which are faster than recent gate level models, while preserving the accuracy of the transistor level models to a great extent. An estimation framework is proposed, describing the subthreshold, gate, and junction leakage of recent technology devices. The models are characterized using BSIM compact models and a Monte Carlo process variation description. Each varying BSIM parameter can be described. As an example of use, channel length, oxide thickness, and channel doping are regarded together with the temperature, supply voltage and body voltage. The final macro model needs less than a hundred parameters to capture the leakage behavior of an entire RT component and is still analytically describing the dependence to the process parameters. Compared to SPICE + BSIM, a model prediction is computed up to a hundred times faster for large RT components, and is, depending on the analyzed technology, within 2.1% (for 16-nm LP)–6.8% (for 65-nm bulk) deviation over a wide range of operating conditions and process variation settings.

De novo gastroesophageal reflux disease after sleeve gastrectomy: role of preoperative silent reflux.

Laparoscopic sleeve gastrectomy (LSG) has become the most frequently performed bariatric procedure to date. However, LSG is known to worsen pre-operative and result in de novo gastroesophageal reflux disease (GERD). Pre-operative evaluation reveals a high percentage of silent GERD of so far unknown influence on post-operative GERD. Prospective data of patients undergoing primary LSG between 01/2012 and 12/2015 were evaluated. Pre-operative GERD-specific evaluation consisted of validated questionnaires, upper endoscopy, 24h-pH-manometry, and esophagograms. Patients were followed-up with questionnaires every 6months, upper endoscopies after 1year and 24h-pH-metry after 2years. Silent GERD was defined as esophagitis grade > B and/or abnormal esophageal acid exposure in absence of symptoms. LSG was performed over a 32F bougie, hiatal hernias > 1cm were addressed with posterior hiatoplasty. Excluded were patients with hiatal hernias > 4cm, patients with incorrect anatomy (stenosis, fundus too large) and conversion to RYGB for early leaks. 222 patients were included. Mean follow-up was 32 ± 16months, mean preoperative body mass index 49.6 ± 7.2kg/m2. 116 patients (52%) presented with post-operative GERD-symptoms, of which 85 (73%) had de novo symptoms. Of those, 48 (of 85, 56%) had no preoperative GERD and 37 (of 85, 44%) silent GERD. 57 patients (26%) had neither pre- nor post-operative GERD, 7 (3%) had silent pre-operative and no postop GERD, and in 19 patients (9%) GERD was cured with LSG. 31 patients (14%) stayed symptomatic. Of 56 patients (25%) with pre-operative silent GERD, 37 (of 54, 66%) became symptomatic. LSG leads to a considerable rate of post-operative GERD. De novo-GERD consist of around half of pre-operative silent GERD and completely de novo-GERD. Most patients with pre-operative silent GERD became symptomatic.

Ocular Distribution and Pharmacodynamics of SF0166, a Topically Administered αvβ3 Integrin Antagonist, for the Treatment of Retinal Diseases.

SF0166, a small-molecule αvβ3 antagonist, has physiochemical properties that allow distribution to the posterior segment of the eye after topical administration in an ophthalmic solution. The pharmacodynamics and ocular distribution of SF0166 were evaluated in several cell lines, chick chorioallantoic membrane assays, and models of ocular neovascularization in mice and pigmented rabbits. SF0166 inhibited cellular adhesion to vitronectin across human, rat, rabbit, and dog cell lines with IC50 values of 7.6 pM to 76 nM. SF0166 inhibited integrin-ligand interactions at IC50 values of 0.6-13 nM for human αvβ3, αvβ6, and αvβ8 SF0166 significantly decreased neovascularization in the oxygen-induced retinopathy mouse model. SF0166 distributed to the choroid and retina after topical ocular administration in amounts that substantially exceeded the cellular IC50 for adhesion to vitronectin; drug concentrations were maintained for >12 hours. In the laser-induced choroidal neovascularization model, topical ocular administration of SF0166 decreased lesion area compared with vehicle and was comparable to a bevacizumab injection. In the vascular endothelial growth factor-induced early neovascularization and vascular leakage model, topical ocular application of SF0166 resulted in a dose-dependent reduction in vascular leakage; the highest ocular doses tested showed comparable activity to a bevacizumab injection.