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International medical graduates (IMGs) have been a critical part of the USA healthcare in the past 30 years, especially in small rural and poor counties. However, little to no publications are present on the distribution of these IMGs across general surgery residency programs.All freely accessible information on current residents in accredited general surgery residency programs within the USA with at least a 5-year history was explored for IMGs in the current roster using the AMA residency and fellowship database in 2020. Demographic and geographic data were summarized.A total of 230 general surgery residency program were included. Programs were distributed among 46 (92%) states. Of a total 6304 categorical general surgery residents, 573 (9%) were IMGs. Florida (USA) had the highest total number of current IMG general surgery residents with 64. The highest percentage of current IMG residents was found in Maryland (USA) with 31%. IMGs obtained their medical degrees from 76 different countries worldwide. Grenada was the country with the highest origin of IMGs with 77 residents. Central/North America had the highest origin of IMGs with 217 (38%).IMGs make up a small portion of current general surgery residents in USA programs. Some states host more IMGs than others. Particular countries have contributed more IMGs than others. More research is needed to the challenges facing IMGs and come up with novel solutions for them.

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

The Model End-Stage Liver Disease (MELD) has been widely used to predict the mortality and morbidity of various surgical procedures. We aimed to assess the impact of preoperative MELD score on adverse 30-day postoperative outcomes following gastrectomy.Patients who underwent elective, non-emergent gastrectomy were identified from the ACS NSQIP 2014-2019 database. Patients were categorized according to a calculated MELD score. The primary outcomes of this study were the 30-day overall complications and major complication rates following gastrectomy.Compared to MELD11, patients with MELD ≥11 had significantly higher rates of mortality, any complication, and major complication. MELD score ≥11 was significantly associated with any complication (OR 1.73, p = 0.011) and major complications (1.85, p = 0.014) on multivariate analysis.MELD score ≥11 was associated with poorer outcomes in patients undergoing gastrectomy compared to lower MELD scores.

The use robotics in surgery is gaining momentum. This approach holds substantial promise in pancreas surgery. Robotic surgery for pancreatic lesions and malignancies has become well accepted and is expanding to more and more center annually. The number of centers using robotics in pancreatic surgery is rapidly increasing. The most studied robotic pancreas surgeries are pancreaticoduodenectomy and distal pancreatectomy. Most studies are in their early phases, but they report that robotic pancreas surgery is safe feasible. Robotic pancreas surgery offers several advantages over open and laparoscopic techniques. Data regarding costs of robotics versus conventional techniques is still lacking. Robotic pancreas surgery is still in its early stages. It holds promise to become the new surgical standard for pancreatic resections in the future, however, more research is still needed to establish its safety, cost effectiveness and efficacy in providing the best outcomes.

[Background & Aims] Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period., [Methods] Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected., [Results] A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974–0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994–0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy’s law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%)., [Conclusions] AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management., [Lay summary] Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes., The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, PI18/00901, PI18/01804, PI-0285-2016, PI-0274-2016, PI-0310-2018, PT17/0017/0020) and Agencia Española del Medicamento. CIBERehd and Plataforma ISCIII Ensayos Clinicos are funded by Instituto de Salud Carlos III. MRD holds a Joan Rodes (JR16/00015)/Acción B clinicos investigadores (B-0002-2019) and JSC a Rio Hortega (CM17/00243) research contract from ISCIII and Consejería de Salud de Andalucía.

Objectives Positive autoantibody (AAB) titres are commonly encountered in autoimmune hepatitis (AIH) and in a proportion of drug-induced liver injury (DILI) patients. The underlying mechanism for selective AAB occurrence in DILI is unknown, but could be associated with variations in immune-associated genes. Hence, we aimed to analyse human leucocyte antigen (HLA) allele compositions in DILI with positive (+) and negative (-) AAB titres and in AIH patients. Methods High-resolution genotyping of HLA class I (A, B, C) and II (DRB1, DQB1) loci was performed on 207 DILI and 50 idiopathic AIH patients and compared with 885 healthy Spanish controls. Results Compared with controls, HLA-B*08:01 [ 44 vs. 9.7%, P = 3.7E-13/corrected P-value (P-c) = 1.0E-11], C*07:01 (46 vs. 24%, P = 6.4E-04/P-c = 0.012), DRB1*03:01 (58 vs. 21.5%, P = 5.0E-09/P-c = 1.0E-07) and DQB1*02:01 (56 vs. 22%, P = 6.8E-08/P-c = 9.0E-07) were significantly more frequent in AIH patients. The HLA-A*01:01 frequency was increased in the same population, but did not reach significance after Bonferroni's correction (34 vs. 19%, P = 0.02/P-c = 0.37). Fifty-eight of 207 DILI patients presented positive titres for at least one AAB (predominantly antinuclear antibody 76% and antismooth muscle antibody 28%). There was a tendency towards higher representation of DRB1*14:01 and DQB1*05:03 in DILI AAB(+) compared with DILI AAB- (13.8 vs. 4.0%, P = 0.02/P-c = 0.5; 13.8 vs. 4.7%, P = 0.04/P-c = 0.5). Conclusion The presence of HLA alleles B*08:01, C*07: 01, DRB1*03: 01, DQB1*02: 01 and possibly A*01: 01 enhances the risk of AIH (type 1) in Spanish patients. These alleles form part of the ancestral haplotype 8.1. HLA-DRB1*14:01 and DQB1*05: 03 could potentially increase the risk of positive AAB (particularly antinuclear antibody) in Spanish DILI patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

A formal framework for the analysis of execution traces collected from distributed systems at run-time is presented. We introduce the notions of event and message traces to capture the consistency of causal dependencies between the elements of a trace. We formulate an approach to property testing where a partially ordered execution trace is modeled by a collection of communicating automata. We prove that the model exactly characterizes the causality relation between the events/messages in the observed trace and discuss the implementation of this approach in SDL, where ObjectGEODE is used to verify properties using model-checking techniques. Finally, we illustrate the approach with industrial case studies.

Formal verification is not always applicable to large industrial software systems due to scalability issues and difficulties in formal model and requirements specification. The scalability and model derivation problems could be alleviated by runtime trace analysis, which combines both testing and formal verification. We implement and compare an ad-hoc custom approach and a formal approach to detect common bug patterns in multithreaded Java software. We use the tracing platform of the Eclipse IDE and state-of-the-art model checker Spin.

Resumen Describimos el caso de una mujer de 64 anos diagnosticada previamente de esprue celiaca sin respuesta clinica e histologica a la retirada del gluten de la dieta. La paciente presento historia de diarrea cronica liquida recurrente y, tras continuacion del estudio de la enfermedad, se le diagnostico de colitis colagena. El estudio inmunologico no fue compatible con enfermedad celiaca y no se encontro la etiologia de la atrofia vellositaria intestinal. Nosotros planteamos la posibilidad de que la paciente presentara un proceso inflamatorio panintestinal independiente a la esprue celiaca, consistente en la existencia de infiltrado inflamatorio cronico tanto de intestino delgado como grueso acompanado de desarrollo de banda colagena subepitelial en el colon.

Several pharmaceutical compounds have been shown to exert inhibitory effects on the bile salt export pump (BSEP) encoded by the ABCB11 gene. We analysed the combined effect on drug-induced liver injury (DILI) development of the ABCB11 1331TC polymorphism and the presence of specific chemical moieties, with known BSEP inhibiting properties, in the causative drug.Genotyping using a TaqMan 5' allelic discrimination assay was performed in 188 Spanish DILI patients, 219 healthy controls and 91 sex-, age- and drug-matched controls. A chemical structure analysis was performed for each individual causative drug.The CC genotype was significantly associated with hepatocellular damage [odds ratio (OR) = 2.1, P = 0.001], particularly in NSAID DILI cases (OR = 3.4, P = 0.007). In addition, the CC genotype was found to be significantly linked to DILI development from drugs causing50% BSEP inhibition (OR = 1.8, Pc = 0.011). Of the BSEP inhibitory chemical moieties, 59% of the causative drugs contained a carbocyclic system with at least one aromatic ring, corresponding to 61% of the total cases. The C allele was significantly more frequent in DILI cases containing this chemical moiety, which appear to be conditioned on the ABCB11 1331TC polymorphism in the absence of other BSEP inhibitory structures.Patients carrying the C allele in the ABCB11 1331TC polymorphism are at increased risk of developing hepatocellular type of DILI, when taking drugs containing a carbocyclic system with aromatic rings.

Background & Aims Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. Methods All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. Results Nine patients (mean age 67years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. Conclusions Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.

We report on a tool for generating executable concurrent tests from scenarios specified as message sequence charts. The proposed approach features three steps: 1) Deriving a MSC test implementation from a MSC scenario, 2) Mapping the test implementation into a Promela model, 3) Generating executable test scripts in Java. The generation of an intermediate Promela model allows for model-checking to inspect the test implementation for properties like soundness, fault detection power as well as for consistency checking between different test scenarios. Moreover decoupling the executable test scripts from the scenario specification makes it possible to use different backend code generators to support other scripting languages when needed.

We present an automated framework for the inference of behavioral models from the execution traces of a web-based business application (WBA). The model inference framework consists of a formal approach to infer automata models from traces of WBA`s and an advanced prototype tool set implemented around the data mining engine Weka, the model checker SPIN, the formal language manipulation framework ANTLR and the graph visualization software GraphViz. The traces of a WBA are collected by monitoring the communications in client-server architectures, where a client can be an Internet browser or a service accessing the server side of the application. The inferred models depict both the control and data flow (showing data variations) of the WBA and can be used for its visualization and verification. Finally, we discuss Web-FIM an online deployment of the model inference framework and illustrate the use of the tools with an example.

We present an approach to the inference of automata models of web-based business applications using only execution traces recording the externally observable behavior of such applications. The proposed approach yields behavioral models representing both the control flow of an application and the data variations corresponding to different types of users. We also describe how the obtained models allow the use of verification techniques like model checking in the validation phase using a case study featuring a travel reservation agency.

We describe the case of a 64-year-old woman with a previous diagnosis of celiac sprue and no clinical or histological response to gluten withdrawal. The patient presented a history of longstanding recurrent watery diarrhea and was found to have collagenous colitis after further investigation of her diarrhea. Immunological study was incompatible with celiac disease and no other cause of villous atrophy was found. We suggest that this patient may have a separate disease entity unrelated to celiac sprue and consisting of a pan-intestinal inflammatory disorder characterized by the combination of a chronic inflammatory infiltrate in the small and lower bowel together with a subepithelial collagenous band in the colon.

We present a framework for property testing where a partially ordered execution trace of a distributed system is modeled by a collection of communicating automata. We prove that the model exactly characterizes the causality relation between the events in the observed trace. We present the implementation of this approach in SDL, where ObjectGEODE is used to verify properties, and illustrate the approach with an industrial case study.

The paper reports on an analysis technology based on the tracing approach to test trustworthy requirements of a distributed system. The system under test is instrumented such that it generates events at runtime to enable reasoning about the implementation of these requirements in a later step. Specifically, an event log collected during a system run is converted into a specification of the system. The (trustworthy) requirements of the system must be formally specified by an expert who has sufficient knowledge about the behaviour of the system. The reengineered model of the system and the requirement descriptions are then processed by an off-the-shelf model checker. The model checker generates scenarios that visualize fulfilments or violations of the requirements. A complex example of a concurrent system serves as a case study.

In this paper, we use supervisory control techniques to design a protocol converter, which avoids divergence in a communication systems. A typical application is to design gateways that interface heterogeneous computer networks while minimizing the communication time with the involved parties. As an example, we design a divergence-free converter that interfaces an alternating bit sender and a non-sequenced receiver, and we implement the converter as an asynchronous circuit.

We present the case of a 33-year-old woman who complained of intermittent diarrhea over the previous 8 years and who was diagnosed with common variable immunodeficiency. The woman presented antral atrophic gastritis, partial atrophy of the duodenal villi, nodular lymphoid hyperplasia of the small intestine and lymphocytic colitis. We also review the literature.

P1200 EFFECTIVENESS OF TRIPLE THERAPY WITH BOCEPREVIR OR TELAPREVIR IN A MULTICENTRE CLINICAL PRACTICE COHORT OF HCV TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED HEPATIC FIBROSIS. SVR-12W AFTER TREATMENT C. Fernandez, P. Munoz de Rueda, S. Alonso, M. Prieto, A. Martin-Alvarez, J. Pons, J. Pascasio, M. Serra, M. Romero, P. Conde, I. Carmona, M. Diago, M. Testillano, J. NavarroJarabo, J. Sanchez Ruano, J. Sousa, F. Nogueras, R. Granados, G. Sanchez Antolin, R. Andrade, H. Hallal, M. Marti Arribas, M. del Moral, J. Salmeron. Servicio de Aparato Digestivo, HU Fundacion de Alcorcon, Madrid, Unidad de Apoyo a la Investigacion, HU San Cecilio, Ciber de Enfermedades Hepaticas y Digestivas (CIBERehd), Granada, Unidad de Gestion Cĺinica de Enfermedades Digestivas, H La Fe, Valencia, Unidad de Hepatoloǵia, H Virgen de Arrixaca, Murcia, Unidad de Hepatoloǵia, H Virgen del Rocio, Sevilla, H Cĺinico de Valencia, Valencia, H Nuestra Senora de Valme, CIBERehd, Sevilla, H Virgen de la Concha, Zamora, Servicio de Aparato Digestivo, HU Virgen de la Macarena, Sevilla, H General de Valencia, Valencia, HU de CRUCES, Bilbao, Vizcaya, Unidad de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Malaga, Servicio de Aparato Digestivo, Complejo Hospitalario de Toledo, Toledo, Servicio de Digestivo, HU Virgen de las Nieves, Granada, HU Gran Canaria Dr. Negŕin, Las Palmas de Gran Canaria, Unidad de Hepatologia, HU Ŕio Hortega, Valladolid, HU Virgen de la Victoria, Malaga, H Morales Meseguer, Murcia, HU Salamanca, Salamanca, Unidad de Gestion Cĺinica de Aparato Digestivo, HU San Cecilio, Ciber de Enfermedades Hepaticas y Digestivas (Ciberehd), Granada, Spain E-mail: fsalmero@ugr.es

Hypercoagulability is a extraintestinal manifestation of inflammatory bowel disease, which could provoke thromboembolic phenomena. Central nervous system venous thrombosis is a rare complication and could be unnoticed. We report on a patient with ulcerative colitis who presented cerebral venous sinus thrombosis as the first manifestation of a hypercoagulable state. We review the literature and discuss about the pathogenic mechanisms of such complication.

During blunt abdominal trauma the small bowel and/or its mesentery may be injured; if abdominal trauma occurs after compression by an incorrectly-applied seat belt, underlying viscera may be crushed between the vertebral and the seat belt; ischemia or infarction of the intestinal wall, and delayed fibrosis and stenosis may occur. We present a patient, operated on two months after blunt abdominal trauma, with small bowel obstruction secondary to post-traumatic intestinal fibrosis. Assuming that this condition is rarely suspected, a delayed diagnosis and treatment of these patients may occur.

A case of idiopathic granulomatous vasculitis (disseminated visceral giant cell arteritis) is described in an old woman, the seventh case of this rare disorder reported to date. The main organ affected was the liver and, to our knowledge, this is the first patient to be diagnosed while still alive and the only case to have received medical treatment. It is also the first time that muscular involvement has been documented in this condition. Cyclophosphamide treatment resulted in disappearance of symptoms and increase in weight. The patient died of an unrelated condition.

Galactorrhea as the result of hyperprolactinemia has been described in very rare cases associated to acute outbreaks of intermittent acute porphyria (IAP). In our country, any of such cases have been published or analytically documented. We present the case of a patient admitted in our hospital for the study of abdominal pain and galactorrhea, with latter diagnosis of IAP, supported by the assessment of the activity of the enzyme showing a deficit in the red blood cells.