A Novel Patient-like Swine Model of Perianal Crohn's Disease.

BACKGROUND: Perianal Crohn's disease is associated with poor outcomes and high medical costs. It is notoriously difficult to treat despite therapeutic advancements for luminal disease. A large animal model that mimics human perianal disease is needed to test innovative therapies. OBJECTIVE: This study aimed to create a swine model that replicates the inflammatory component and therapeutic challenges found in patients with perianal Crohn's disease. DESIGN: This was an animal preclinical study. SETTINGS: The experiments were performed at the animal laboratory at the Johns Hopkins University. PATIENTS: Four sus scrufus female pigs were included in the study. INTERVENTIONS: Four female pigs underwent creation of 3 surgical perianal fistulas each, 1 rectovaginal and 2 perianal. Size 24 French setons were placed to maintain patency of the fistula tracts for 4 weeks. After removal of the setons, trinitrobenzene sulfonic acid was administered into the fistula tract to create and maintain local inflammation mimicking perianal Crohn's disease. MAIN OUTCOMES MEASURES: An MRI was obtained to assess the fistulas and the pigs were euthanized to review histopathology. RESULTS: Three inflammatory chronic fistula tracts were successfully created in each pig as confirmed by MRI and examination under anesthesia. This is the first report of maintaining patent fistulas in swine 2 weeks after removal of setons. For the first time, we reported that 2 pigs developed branching fistulas and small abscesses reminiscent of human perianal Crohn's disease. The corresponding histopathologic examination found significant chronic active inflammation on standard hematoxylin and eosin staining. LIMITATIONS: The fistulas were surgically induced and did not occur naturally. CONCLUSIONS: A chronic perianal fistula model in pigs that strongly resembles human perianal Crohn's disease was successfully created. This model can be used to test novel therapeutics and techniques to pave the path for human trials. See Video Abstract at http://links.lww.com/DCR/B969 . UN NUEVO MODELO PORCINO SIMILAR A UN PACIENTE DE LA ENFERMEDAD DE CROHN PERIANAL ANTECEDENTES: La enfermedad de Crohn perianal se asocia con malos resultados y altos costos médicos. Es notoriamente difícil de tratar a pesar de los avances terapéuticos para la enfermedad luminal. Se precisa de un modelo animal grande que imite la enfermedad perianal humana para probar terapias innovadoras.OBJETIVO:Nuestro objetivo de este estudio fue crear un modelo porcino que replique el componente inflamatorio y los desafíos terapéuticos que se encuentran en los pacientes con enfermedad de Crohn perianal.DISEÑO:Este fue un estudio preclínico en animales.AJUSTES:Los experimentos se realizaron en el laboratorio de animales de la Universidad Johns Hopkins.PACIENTES:Se incluyeron en el estudio cuatro cerdas sus scrofa.INTERVENCIONES:Cuatro cerdas fueron sometidas a la creación de 3 fístulas perianales quirúrgicas cada una: 1 recto vaginal y 2 perianales. Se colocaron sedales de 24 French para mantener la permeabilidad de los trayectos fistulosos durante 4 semanas. Tras el retiro de los sedales, se administró ácido trinitrobenceno sulfónico en el trayecto de la fístula para crear y mantener la inflamación local simulando la enfermedad de Crohn perianal.PRINCIPALES MEDIDAS DE RESULTADOS:Se obtuvo una resonancia magnética para evaluar las fístulas y los cerdos fueron sacrificados para revisar la histopatología.RESULTADOS:Se crearon de manera exitosa tres trayectos fistulosos inflamatorios crónicos en cada cerdo, confirmados por imágenes de resonancia magnética y examen bajo anestesia. Este es el primer informe de preservación de fístulas permeables en cerdos 2 semanas tras el retiro de los setones. Por primera vez, informamos que dos cerdos desarrollaron fístulas ramificadas y pequeños abscesos que recuerdan a la enfermedad de Crohn perianal humana. El examen histopatológico correspondiente encontró una significativa inflamación crónica activa en la tinción estándar de hematoxilina y eosina.LIMITACIONES:Las fístulas se indujeron quirúrgicamente y no se produjeron de forma natural.CONCLUSIONES:Se logro recrear con éxito un modelo de fístula perianal crónica en cerdos que se asemeja mucho a la enfermedad de Crohn perianal humana. Este modelo se puede utilizar para probar nuevas terapias y técnicas para allanar el camino para los ensayos en humanos. Consulte Video Resumen en http://links.lww.com/DCR/B969 . (Traducción-Dr Osvaldo Gauto).

Orbital Myositis in a Patient With Ileal Crohn's Disease in Remission on Vedolizumab.

Orbital myositis (OM) is an extremely rare ocular extraintestinal manifestation of inflammatory bowel disease. Acute or chronic inflammation of one or more extraocular muscles leads to symptoms related to the mass effect including orbital pain, swelling, ophthalmoplegia, proptosis, and diplopia. Although the use of steroids typically leads to rapid resolution of symptoms, recurrence is common, necessitating long-term steroid-sparing therapies. Given the rare presentation of OM, its pathogenesis and optimal therapy are not well established. We present a young woman with Crohn's disease in remission on vedolizumab who developed OM, and we discuss our management approach.

Association Between Immunosuppressive Therapy and Outcome of Clostridioides difficile Infection: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM: To determine the association between immunosuppressive therapy and CDI outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.

A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics.

Gastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.

Management of Asymptomatic Terminal Ileitis.

Ileal intubation is often performed during screening colonoscopies. This had led to the recognition of mild ileitis in many asymptomatic patients. The natural history and clinical significance of this finding are not well established, and there are no guidelines on whether these patients merit further work-up or an interval surveillance colonoscopy. This conundrum was presented and discussed on @MondayNightIBD. In this article, we review the specific literature on the topic and make reference to the informed opinions of the convo participants. We propose an #IBDAlgorithm for management of asymptomatic ileitis.

#MondayNightIBD: Management of Chronic #Pouchitis.

We present a #MondayNightIBD case of chronic pouchitis and discuss key diagnostic and therapeutic challenges commonly encountered in clinical practice. We make reference not only to the limited published literature but also to the informed opinions of the #MondayNightIBD discussion participants, identifying gaps where management guidelines and research are needed. A #MondayNightIBD Algorithm for Pouchitis Management is proposed.

Pancreatic Pseudocysts and Parenchymal Necrosis in Patients With Autoimmune Pancreatitis: A Systematic Review.

OBJECTIVE: To investigate the prevalence and natural history of pancreatic pseudocysts (PCs) and parenchymal necrosis in autoimmune pancreatitis (AIP). METHOD: A search using PubMed, Embase, Scopus, and Cochrane was performed. Search terms were AIP, PC, acute fluid collection, and pancreatic necrosis. RESULTS: Fifteen studies with 17 patients were included. In 8 of 17 patients, PC was noted concurrently with the AIP diagnosis, whereas in the other half, PC appeared months or years after. In 10 of 17 cases, PC appeared as solitary. The location was variable. Pseudocysts were small (<3 cm) in 4 cases and large (>3 cm) in 13 cases. A normal pancreatic duct was observed in 6 of 17 cases, whereas 9 of 17 had pancreatic duct stenosis. Steroids were given to 4 of 4 small and 10 of 13 large PC. All small PC resolved with steroids, whereas only 4 of 10 large PC treated had some response. Most (9/13) of large PC underwent endoscopic or surgical procedures. None of the 17 cases developed necrosis. CONCLUSIONS: Pseudocysts in AIP are rare. Pancreatic pseudocyst can present in variable number, size, and location. Small PC resolved with steroids. Large PC had poor response to steroids requiring invasive interventions. Necrosis in AIP has not been reported.

Muscle-derived extracellular superoxide dismutase inhibits endothelial activation and protects against multiple organ dysfunction syndrome in mice.

Multiple organ dysfunction syndrome (MODS) is a detrimental clinical complication in critically ill patients with high mortality. Emerging evidence suggests that oxidative stress and endothelial activation (induced expression of adhesion molecules) of vital organ vasculatures are key, early steps in the pathogenesis. We aimed to ascertain the role and mechanism(s) of enhanced extracellular superoxide dismutase (EcSOD) expression in skeletal muscle in protection against MODS induced by endotoxemia. We showed that EcSOD overexpressed in skeletal muscle-specific transgenic mice (TG) redistributes to other peripheral organs through the circulation and enriches at the endothelium of the vasculatures. TG mice are resistant to endotoxemia (induced by lipopolysaccharide [LPS] injection) in developing MODS with significantly reduced mortality and organ damages compared with the wild type littermates (WT). Heterogenic parabiosis between TG and WT mice conferred a significant protection to WT mice, whereas mice with R213G knock-in mutation, a human single nucleotide polymorphism leading to reduced binding EcSOD in peripheral organs, exacerbated the organ damages. Mechanistically, EcSOD inhibits vascular cell adhesion molecule 1 expression and inflammatory leukocyte adhesion to the vascular wall of vital organs, blocking an early step of the pathology in organ damage under endotoxemia. Therefore, enhanced expression of EcSOD in skeletal muscle profoundly protects against MODS by inhibiting endothelial activation and inflammatory cell adhesion, which could be a promising therapy for MODS.

[Update on chronic pancreatitis: review article]. / Una actualización de pancreatitis crónica: artículo de revisión.

Chronic pancreatitis is a progressive fibro-inflammatory disease of the pancreas characterized by irreversible fibrosis of the gland with eventual failure of exocrine and endocrine functions and hallmark features of abdominal pain, malabsorption, malnutrition, diabetes mellitus and pancreatic calcifications. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals), genetic factors and a few patients with hereditary or autoimmune disease. The management includes medical, endoscopic and surgical approaches with the need for interaction between various specialties, calling for a concerted multidisciplinary approach. This review provides the reader with a comprehensive overview of the studies summarizing the epidemiology, etiology, physiopatology, clinical manifestation, diagnosis and treatments of the disease.

Una actualización de pancreatitis crónica: artículo de revisión / Update on chronic pancreatitis: review article

La pancreatitis crónica es una enfermedad fibro-inflamatoria progresiva del páncreas caracterizada por la fibrosis irreversible de la glándula con el eventual fallo de las funciones exocrinas y endocrinas. Las características distintivas de la enfermedad son el dolor abdominal, la malabsorción, la desnutrición, la diabetes mellitus y las calcificaciones pancreáticas. En muchos pacientes el origen de esta enfermedad se debe a una compleja mezcla de factores ambientales (por ejemplo, alcohol, cigarrillos y productos químicos en el trabajo), factores genéticos y en algunos casos origen hereditario o autoinmune. El manejo incluye enfoques médico, endoscópico y quirúrgico con la necesidad de la interacción entre diversas especialidades para dar un enfoque multidisciplinario coordinado. Esta revisión ofrece una visión general de los estudios recientes resumiendo la epidemiología, etiología, fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento de la enfermedad.

Chronic pancreatitis is a progressive fibro-inflammatory disease of the pancreas characterized by irreversible fibrosis of the gland with eventual failure of exocrine and endocrine functions and hallmark features of abdominal pain, malabsorption, malnutrition, diabetes mellitus and pancreatic calcifications. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals), genetic factors and a few patients with hereditary or autoimmune disease. The management includes medical, endoscopic and surgical approaches with the need for interaction between various specialties, calling for a concerted multidisciplinary approach. This review provides the reader with a comprehensive overview of the studies summarizing the epidemiology, etiology, physiopatology, clinical manifestation, diagnosis and treatments of the disease.

Clinicopathological Spectrum of Mitral Valve Myxoma.

Cardiac myxomas are the most common primary tumors of the heart. Although these tumors have been reported in all cardiac chambers, myxomas arising from heart valves are extremely rare. Here, the details are described of a patient with mitral valve myxoma, and a review is provided of 99 cases reported in the literature. Mitral valve myxomas most often occur in middle-aged patients, with a slight female predominance. Most of the tumors arise in an isolated fashion on the atrial side of the anterior mitral valve leaflet. Embolic events were the most frequent manifestation, followed by obstructive symptoms. Unlike atrial wall myxomas, these tumors have a lower incidence of constitutional manifestations. Tumor resection with valve preservation is the usual method of surgical treatment in isolated tumors, while most patients with multiple valve myxomas underwent valve replacement. Mitral valve myxomas should be considered in the differential diagnosis of mitral valve tumors, with an awareness of a relatively high risk of embolic events. This location should not raise suspicion for a heritable myxoma syndrome. Prompt surgical resection is warranted to reduce complications.

Type 1 autoimmune pancreatitis: case scenario and review of the disease.

Autoimmune pancreatitis (AIP) is an uncommon disease that represents a diagnostic challenge unless it is considered as a cause of acute pancreatitis, pancreatic exocrine insufficiency and a pancreatic mass. This entity is under diagnosed and successful medical therapy is available. In this paper, we will describe a case of a 59 year-old, Hispanic woman diagnosed with autoimmune pancreatitis, a disease previously believed to affect typically older men. We will review the definition, types, clinical manifestations, radiological features, serology, histopathological findings, treatment strategies and diagnostic criteria of autoimmune pancreatitis.

Henoch-Schönlein Purpura with Adalimumab Therapy for Ulcerative Colitis: A Case Report and Review of the Literature.

Tumor necrosis factor-α (TNFα) inhibitor therapy has signified an important milestone in the fight against many rheumatological disorders and inflammatory bowel disease (IBD). Cutaneous adverse events caused by this class of medications are well known but relatively uncommon. Most reactions are mild and rarely warrant treatment withdrawal. Henoch-Schönlein purpura (HSP) is a disease with cutaneous vasculitis, arthritis, and gastrointestinal and renal involvement that is usually seen in children, though the worst complications are typically seen in adults. We present a case of HSP complicating adalimumab treatment in a patient with ulcerative colitis who had achieved endoscopic remission. We review similar cases reported in the literature and discuss the consequences of these autoimmune diseases.

Type 1 autoimmune pancreatitis: case scenario and review of the disease

Autoimmune pancreatitis (AIP) is an uncommon disease that represents a diagnostic challenge unless it is considered as a cause of acute pancreatitis, pancreatic exocrine insufficiency and a pancreatic mass. This entity is under diagnosed and successful medical therapy is available. In this paper, we will describe a case of a 59 year-old, Hispanic woman diagnosed with autoimmune pancreatitis, a disease previously believed to affect typically older men. We will review the definition, types, clinical manifestations, radiological features, serology, histopathological findings, treatment strategies and diagnostic criteria of autoimmune pancreatitis

La pancreatitis autoinmune (PAI) es una enfermedad rara que se presenta como un reto diagnóstico a menos que sea considerada como causa de pancreatitis aguda, insuficiencia pancreática exocrina y masa pancreática. Es una enfermedad sub diagnosticada y existe una terapia médica satisfactoria. En este trabajo, describiremos un caso de una mujer hispana de 59 años diagnosticada de pancreatitis autoinmune, una enfermedad que se creía previamente que afectaba típicamente a hombres de avanzada edad. Revisaremos la definición, los tipos, las manifestaciones clínicas, hallazgos radiológicos, serología, hallazgos histopatológicos, estrategias de tratamiento y criterios diagnósticos de la pancreatitis autoinmune

Hepatotoxicity by herbs: a practical review of a neglected disease.

Herbs are commonly used worldwide for the treatment of various diseases, constituting a multi-billion dollar market. Unfortunately, hepatotoxicity induced by herbs is also common. The true incidence and prevalence are not known. There is need for more strict regulations andexperimental and pre-clinical studies regarding its efficacy and safety. There is no gold standard for the diagnosis of herbs-induced liver injury (HILI) and it constitutes a diagnostic challenge for the clinician, whereestablishing causality could be cumbersome. Clinical presentation varies from asymptomatic cases with mildly abnormal liver tests to fulminant liver failure requiring liver transplantation. In this review, we will discuss the epidemiology, clinical manifestations, challenges and diagnostic approach of HILI and will also present some exemplary cases from the University of Miami, Division of Hepatology.

[Acute respiratory distress syndrome due to Clostridium difficile colitis: a case report and review of the literature]. / Síndrome de distress respiratorio agudo debido a colitis por Clostridium difficile: reporte de caso y revisión de la literatura.

Clostridium difficile is a major cause of antibiotic-associated diarrhea. We report a patient with complicated Clostridium difficile infection (CDI) who developed rapidly progressive acute respiratory distress syndrome (ARDS), for which CDI was the only identifiable source. CDI should be considered in the differential diagnosis for anyone with diarrhea who presents especially in high-risk groups such as the elderly, hospitalized patients, or those who have had a history of CDI.

Acute respiratory distress syndrome due to Clostridium difficile colitis: a case report and review of the literature / Síndrome de distress respiratorio agudo debido a colitis por Clostridium difficile: reporte de caso y revisión de la literatura

Clostridium difficile is a major cause of antibiotic-associated diarrhea. We report a patient with complicated Clostridium difficile infection (CDI) who developed rapidly progressive acute respiratory distress syndrome (ARDS), for which CDI was the only identifiable source. CDI should be considered in the differential diagnosis for anyone with diarrhea who presents ARDS, especially in high-risk groups such as the elderly, hospitalized patients, or those who have had a history of CDI.

El Clostridium difficile es una de las causas más frecuentes de diarreas asociadas a antibióticos. Reportamos un paciente con infección por Clostridium difficile complicada (CDI) que desarrolló rápida y progresivamente un síndrome de distress respiratorio agudo (ARDS), del cual el CDI fue la fuente única identificable. El CDI debe considerarse en el diagnóstico diferencial de cualquier persona con diarrea que presenta ARDS, especialmente en los grupos de alto riesgo como los ancianos, pacientes hospitalizados o aquellos que han tenido historia precia de DCI.

Extracellular superoxide dismutase ameliorates skeletal muscle abnormalities, cachexia, and exercise intolerance in mice with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is a leading cause of morbidity and mortality, and oxidative stress has been implicated in the pathogenesis of cachexia (muscle wasting) and the hallmark symptom, exercise intolerance. We have previously shown that a nitric oxide-dependent antioxidant defense renders oxidative skeletal muscle resistant to catabolic wasting. Here, we aimed to identify and determine the functional role of nitric oxide-inducible antioxidant enzyme(s) in protection against cardiac cachexia and exercise intolerance in CHF. METHODS AND RESULTS: We demonstrated that systemic administration of endogenous nitric oxide donor S-nitrosoglutathione in mice blocked the reduction of extracellular superoxide dismutase (EcSOD) protein expression, as well as the induction of MAFbx/Atrogin-1 mRNA expression and muscle atrophy induced by glucocorticoid. We further showed that endogenous EcSOD, expressed primarily by type IId/x and IIa myofibers and enriched at endothelial cells, is induced by exercise training. Muscle-specific overexpression of EcSOD by somatic gene transfer or transgenesis (muscle creatine kinase [MCK]-EcSOD) in mice significantly attenuated muscle atrophy. Importantly, when crossbred into a mouse genetic model of CHF (α-myosin heavy chain-calsequestrin), MCK-EcSOD transgenic mice had significant attenuation of cachexia with preserved whole body muscle strength and endurance capacity in the absence of reduced HF. Enhanced EcSOD expression significantly ameliorated CHF-induced oxidative stress, MAFbx/Atrogin-1 mRNA expression, loss of mitochondria, and vascular rarefaction in skeletal muscle. CONCLUSIONS: EcSOD plays an important antioxidant defense function in skeletal muscle against cardiac cachexia and exercise intolerance in CHF.