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BACKGROUND AND AIMS: Direct endoscopic necrosectomy (DEN) is a recommended strategy for treatment of walled-off necrosis (WON). DEN uses a variety of devices including the EndoRotor (Interscope, Inc, Northbridge, Mass, USA) debridement catheter. Recently, a 5.1-mm EndoRotor with an increased chamber size and rate of tissue removal was introduced. The aim of this study was to assess the efficacy and safety of this device. METHODS: A multicenter cohort study was conducted at 8 institutions including patients who underwent DEN with the 5.1-mm EndoRotor. The primary outcome was the number of DEN sessions needed for WON resolution. Secondary outcomes were the average percentage of reduction in solid WON debris and decrease in WON area per session, total time spent performing EndoRotor therapy for WON resolution, and adverse events (AEs). RESULTS: Sixty-four procedures in 41 patients were included. For patients in which the 5.1-mm EndoRotor catheter was the sole therapeutic modality, an average of 1.6 DEN sessions resulted in WON resolution with an average cumulative time of 85.5 minutes. Of the 21 procedures with data regarding percentage of solid debris, the average reduction was 85% ± 23% per session. Of the 19 procedures with data regarding WON area, the mean area significantly decreased from 97.6 ± 72.0 cm2 to 27.1 ± 35.5 cm2 (P < .001) per session. AEs included 2 intraprocedural dislodgements of lumen-apposing metal stents managed endoscopically and 3 perforations, none of which was related to the EndoRotor. Bleeding was reported in 7 cases, in which none required embolic or surgical therapy and 2 required blood transfusions. CONCLUSIONS: This is the first multicenter retrospective study to investigate the efficacy and safety of the 5.1-mm EndoRotor catheter for WON. Results from this study showed an average of 1.6 DEN sessions were needed to achieve WON resolution with an 85% single-session reduction in solid debris and a 70% single-session decrease in WON area with minimal AEs.
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Catéteres , Desbridamiento , Pancreatitis Aguda Necrotizante , Humanos , Masculino , Femenino , Persona de Mediana Edad , Desbridamiento/métodos , Pancreatitis Aguda Necrotizante/cirugía , Pancreatitis Aguda Necrotizante/terapia , Anciano , Adulto , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de CohortesRESUMEN
Skin substitutes including allografts remain a standard therapeutic approach to promote healing of both acute and chronic large wounds. However, none have resulted in the regrowth of lost and damaged tissues and scarless wound healing. Here, we demonstrate skin allograft chimerism and repair through the mobilization of endogenous bone marrow-derived stem and immune cells in rats and swine. We show that pharmacological mobilization of bone marrow stem cells and immune cells into the circulation promotes host repopulation of skin allografts and restoration of the skin's normal architecture without scarring and minimal contracture. When skin allografts from DA rats are transplanted into GFP transgenic Lewis recipients with a combination of AMD3100 and low-dose FK506 (AF) therapy, host-derived GFP-positive cells repopulate and/or regenerate cellular components of skin grafts including epidermis and hair follicles and the grafts become donor-host chimeric skin. Using AF combination therapy, burn wounds with skin allografts were healed by newly regenerated chimeric skin with epidermal appendages and pigmentation and without contracture in swine.
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Quemaduras , Contractura , Ratas , Animales , Porcinos , Trasplante de Médula Ósea , Médula Ósea , Quimerismo , Ratas Endogámicas Lew , Quemaduras/cirugía , Trasplante de Piel , Aloinjertos , Células Madre , Supervivencia de InjertoRESUMEN
The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.
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Hepatitis Alcohólica , Humanos , Escherichia coli , Inmunoglobulina A , Autoanticuerpos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
Preclinical studies demonstrate that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a fixed-dose drug combination (MRG-001) improves wound healing, promotes tissue regeneration, and prevents allograft rejection. In this phase I, first-in-human study, three cohorts receive subcutaneous MRG-001 or placebo, every other day for 5 days. The primary outcome is safety and tolerability of MRG-001. Fourteen subjects received MRG-001 and seven received a placebo. MRG-001 is safe over the selected dose range. There are no clinically significant laboratory changes. The intermediate dose group demonstrates the most significant white blood cell, stem cell, and immunoregulatory cell mobilization. PBMC RNA sequencing and gene set enrichment analysis reveal 31 down-regulated pathways in the intermediate MRG-001 dose group compared with no changes in the placebo group. MRG-001 is safe across all dose ranges. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration (ClinicalTrials.gov: NCT04646603).
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Leucocitos Mononucleares , Células Madre , Humanos , Voluntarios Sanos , Trasplante HomólogoRESUMEN
The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We sought to determine if there was antibody deposition in SAH livers and whether antibodies extracted from SAH livers were cross-reactive against both bacterial antigens and human proteins. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissue from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. Employing human proteome arrays, we profiled the antibodies extracted from explanted SAH, alcoholic cirrhosis (AC), nonalcoholic steatohepatitis (NASH), primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), hepatitis B virus (HBV), hepatitis C virus (HCV) and HD livers and found that antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins as autoantigens. The use of an E. coli K12 proteome array revealed the presence of unique anti- E. coli antibodies in SAH, AC or PBC livers. Further, both Ig and E. coli captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion and focal adhesion (IgG). Except IgM from PBC livers, no common autoantigen was recognized by Ig and E. coli captured Ig from AC, HBV, HCV, NASH or AIH suggesting no cross-reacting anti- E. coli autoantibodies. The presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in the liver may participate in the pathogenesis of SAH.
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The lymph node (LN) is an intriguing site not only for inducing protective effector immunity but also for inducing tolerance against peripherally encountered antigens such as tissue-specific self-antigens that are regionally drained and through draining lymph nodes (DLNs). The dual functions of DLNs in immunity are attributable at least in part to fibroblastic reticular cells (FRCs), which are a major population of the nonhematopoietic compartment in the LN. In this issue of the JCI, Li, Zhao, and colleagues investigated DLNs in the transplantation setting. The authors demonstrated that, following skin transplantation, the donor mast cell-mediated senescence in FRCs was associated with collagen 1 deposition in DLNs. Systemic administration to mice of FRCs that were expanded ex vivo decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data implicate the DLN as a target for immunomodulatory therapy of transplant rejection.
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Ganglios Linfáticos , Trasplante de Órganos , Animales , Colágeno , Fibrosis , Ratones , Ratones Endogámicos C57BLRESUMEN
Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow-derived CD133+ and CD34+ endothelial progenitor cells and Ym1/2+ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.
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Diabetes Mellitus Experimental/fisiopatología , Pie Diabético/fisiopatología , Células Progenitoras Endoteliales/efectos de los fármacos , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/farmacología , Tacrolimus/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Bencilaminas , Ciclamas , Femenino , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Adhesions are a very common complication in the abdominal surgery. Animal studies and human trials have evaluated strategies designed to reduce and prevent postsurgical adhesions but few have an evidence base that justifies routine use. A strategy to prevent adhesions effectively remains an urgent need. We studied a reproducible model of intra-peritoneal adhesion formation in rats using laparotomy with several peritoneal sutures to produce the adhesions. Here we show that entraining endogenous stem cells into injury sites using the combined effect of AMD3100 and low-dose FK-506 (AF) can reduce the adhesion score significantly and abolish peritoneal adhesions in 45% of animals in a rat model of severe postsurgical intra-abdominal adhesions, compared with saline controls. Searching for mechanisms, we found AF treatment dramatically increased SDF-1 expressing cells, HGF expressing Ym1+ M2 macrophages and CD133+ stem cells in the injury sites of peritoneal surface at day 5 post-operation. Our results demonstrate that medically induced recruitment of autologous stem cells using AF significantly reduced postsurgical intra-abdominal adhesions. These findings suggest a novel effective therapeutic approach to preventing adhesions in patients.
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Compuestos Heterocíclicos/uso terapéutico , Peritoneo/cirugía , Células Madre/metabolismo , Tacrolimus/uso terapéutico , Adherencias Tisulares/tratamiento farmacológico , Antígeno AC133/metabolismo , Abdomen/patología , Animales , Bencilaminas , Estudios de Casos y Controles , Quimiocina CXCL12/metabolismo , Ciclamas , Modelos Animales de Enfermedad , Factor de Crecimiento de Hepatocito/metabolismo , Compuestos Heterocíclicos/farmacología , Laparotomía , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/metabolismo , Peritoneo/metabolismo , Ratas , Ratas Endogámicas Lew , Células Madre/citología , Tacrolimus/farmacología , Adherencias Tisulares/patologíaRESUMEN
BACKGROUND: Endoscopically or fluoroscopically guided dilation is a safe and effective alternative to surgery for patients with benign strictures of the gastric outlet. CASE SUMMARY: We describe two cases where a novel approach with a Spyglass® choledochoscope in assessing the extent of benign duodenal strictures and aiding in placement of duodenal stents for treatment of the strictures. Choledochoscope-guided wire and stent placement was successful in all cases, leading to symptom resolution related to benign duodenal obstruction. No major adverse events were observed. CONCLUSION: Choledochoscope-guided assessment and endoscopic therapy is a viable approach in relieving duodenal obstruction, if the conventional combined fluoroscopic and endoscopic methods fail.
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BACKGROUND: Endoluminal vacuum therapy (EVAC) is an emerging procedure used to treat anastomotic leaks and/or perforations that would otherwise require surgery. The aim of this study was to determine time to proficiency in EVAC and the cost effectiveness of the procedure. METHODS: We retrospectively reviewed a prospectively maintained IRB approved database for all patients undergoing EVAC after esophageal and gastric complications between October 2013 and December 2017. Proficiency was determined by obtaining predicted estimates and analyzing the point at which average procedure time plateaued based on case volume. Total cost was calculated based on supplies and location where the procedure was performed. RESULTS: There were 50 patients (17 males, 33 female), with a mean age of 52.1 years. EVAC was placed in 23 (46%) patients with esophageal injuries and 28 (56%) with gastric injuries. Two advanced endoscopists performed all EVAC procedures in this study (1 surgeon, 1 gastroenterologist). The average procedure time for all patients was 43.5 min and the average wheel in/wheel out time for all patients was 75.6 min. Analysis of the trend based on average procedure times for EVAC revealed that proficiency was obtained after 10 cases. Total cost of the procedure is significantly lower in the GI lab compared to the operating room ($4528 vs. $11889). The majority of EVAC were performed in the GI lab (62%) compared to the operating room (38%). CONCLUSION: Successful outcomes in managing anastomotic leaks or intestinal perforations non-operatively has led to an increased interest in EVAC. For advanced endoscopists, time to proficiency is approximately 10 cases. Performing the procedure in the GI lab has a 2.5 reduction in total cost compared to the operating room.
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Fuga Anastomótica , Endoscopía , Esófago , Terapia de Presión Negativa para Heridas , Estómago , Técnicas de Cierre de Heridas , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Análisis Costo-Beneficio , Endoscopios , Endoscopía/economía , Endoscopía/instrumentación , Endoscopía/métodos , Esófago/lesiones , Esófago/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia de Presión Negativa para Heridas/economía , Terapia de Presión Negativa para Heridas/métodos , Estudios Retrospectivos , Estómago/lesiones , Estómago/cirugía , Resultado del Tratamiento , Técnicas de Cierre de Heridas/economía , Técnicas de Cierre de Heridas/instrumentaciónRESUMEN
INTRODUCTION: Severe burns are often associated with high morbidity and unsatisfactory functional and esthetic outcomes. Over the last two decades, stem cells have generated great hopes for the treatment of numerous conditions including burns. The aim of this systematic review is to evaluate the role of stem cell therapy as a means to promote burn wound healing. METHODS: Comprehensive searches in major databases were carried out in March 2017 for articles on stem cell therapy in burn wound healing. In total 2103 articles were identified and screened on the basis of pre-determined inclusion and exclusion criteria. RESULTS: Fifteen experimental and two clinical studies were included in the review. The majority of studies reported significant improvement in macroscopic burn wound appearance as well as a trend toward improved microscopic appearance, after stem cell therapy. Other parameters evaluated, such as re-vascularization, collagen formation, level of pro- and anti-inflammatory mediators, apoptosis and cellular infiltrates, yielded heterogeneous results across studies. CONCLUSION: Stem cell therapy appears to exert a positive effect in burn wound healing. There is, therefore, justification for continued efforts to evaluate the use of stem cells as an adjunct to first-line therapies in burns.
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Quemaduras/terapia , Trasplante de Células Madre , Cicatrización de Heridas , Tejido Adiposo/citología , Animales , Trasplante de Médula Ósea , Humanos , Trasplante de Células Madre Mesenquimatosas , RegeneraciónRESUMEN
Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.08 1.381.78 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.
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Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Potencial de la Membrana Mitocondrial , Complicaciones Posoperatorias , Adulto , Funcionamiento Retardado del Injerto/patología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/patología , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Perfusión , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Donantes de Tejidos , Obtención de Tejidos y Órganos , Receptores de Trasplantes , Adulto JovenRESUMEN
BACKGROUND: To investigate the efficacy of primary and rescue endoluminal vacuum (EVAC) therapy in the treatment of esophageal perforations and leaks. METHODS: We conducted a retrospective review of a prospectively gathered, Institutional Review Board (IRB) approved database of EVAC therapy patients at our center from July 2013 to September 2016. RESULTS: In all, 13 patients were treated for esophageal perforations or leaks. Etiologies included iatrogenic injury (n = 8), anastomotic leak (n = 2), Boerhaave syndrome (n = 1), and bronchoesophageal fistula (n = 2). In total, 10 patients underwent primary treatment and three were treated with rescue therapy. Mean Perforation Severity Scores (PSSs) in the primary and rescue treatment groups were 7 and 10, respectively. Average defect size was 2.4 (range: 0.5-6) cm. The rescue group had a shorter mean time to defect closure (25 vs. 33 days). In all, 12 of 13 defects healed. One death occurred following the implementation of comfort care. One therapy-specific complication occurred. Hospital length of stay (LOS) was longer in the rescue group (72 vs. 53 days); however, the intensive care unit (ICU) duration was similar between groups. Totally, 10 patients (83%) resumed an oral diet after successful defect closure. CONCLUSION: Utilized as either a primary or rescue therapy, EVAC therapy appears to be beneficial in the management of esophageal perforations or leaks.
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Fuga Anastomótica/terapia , Fístula Bronquial/terapia , Fístula Esofágica/terapia , Perforación del Esófago/terapia , Esofagoscopía , Enfermedad Iatrogénica , Enfermedades del Mediastino/terapia , Terapia de Presión Negativa para Heridas , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/etiología , Fuga Anastomótica/mortalidad , Fístula Bronquial/etiología , Fístula Bronquial/mortalidad , Bases de Datos Factuales , Fístula Esofágica/etiología , Fístula Esofágica/mortalidad , Perforación del Esófago/etiología , Perforación del Esófago/mortalidad , Esofagoscopía/efectos adversos , Esofagoscopía/instrumentación , Esofagoscopía/mortalidad , Femenino , Humanos , Tiempo de Internación , Masculino , Enfermedades del Mediastino/etiología , Enfermedades del Mediastino/mortalidad , Persona de Mediana Edad , Terapia de Presión Negativa para Heridas/efectos adversos , Terapia de Presión Negativa para Heridas/instrumentación , Terapia de Presión Negativa para Heridas/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tapones Quirúrgicos de Gaza , Factores de Tiempo , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
Laparoscopic sleeve gastrectomy (LSG) is the most common bariatric surgery performed for morbid obesity. Leaks of the vertical staple line can occur in up to 7% of cases and are difficult to manage. Endolumenal vacuum (EVAC) therapy and fistulojejunostomy (FJ) have separate documented uses to heal these complicated leaks. We aim to show the benefit of using EVAC with FJ in the treatment of LSG staple line leaks. The patient presented with an LSG chronic leak. EVAC therapy was initiated but failed to close the fistula after 101 days. EVAC therapy was abandoned, and FJ was performed to resolve the leak. Postoperatively, no leak was encountered requiring any additional procedures. Based on our findings, we conclude that EVAC therapy facilitates in resolving leaks that restore gastrointestinal continuity and maintain source control. It promotes healing and causes reperfusion of ischemic tissue and fistula cavity debridement.
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Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low-dose FK506 (F). Here we show that AF combination therapy significantly increased lineage negative (Lin-) CD34+ and Lin-CD133+ stem cells in peripheral blood and enhanced recruitment of CD133+ cells into the remnant liver in a rat model of 85% partial hepatectomy. Recruiting CD133+ stem cells in the remnant liver was associated with increased proliferation of hepatic oval cells and paralleled the increased SDF-1, CXCR4 and HGF expression. Importantly, AF combination therapy increased the number of Ki67 positive hepatocytes and BrdU incorporation in the remnant liver and improved serum levels of albumin. Our results demonstrate that pharmacological mobilization of endogenous bone marrow stem cells with AF combination therapy can enhance endogenous stem cell mobilization to promote liver regeneration and improve liver function after extensive hepatectomy.
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Células de la Médula Ósea/metabolismo , Movilización de Célula Madre Hematopoyética/métodos , Hepatectomía/rehabilitación , Regeneración Hepática/efectos de los fármacos , Regeneración Hepática/fisiología , Células Madre/metabolismo , Antígeno AC133/metabolismo , Alanina Transaminasa/sangre , Animales , Antígenos CD34/metabolismo , Aspartato Aminotransferasas/sangre , Bencilaminas , Inhibidores de la Calcineurina/farmacología , Proliferación Celular/efectos de los fármacos , Quimiocina CXCL12/metabolismo , Ciclamas , Quimioterapia Combinada , Femenino , Factor de Crecimiento de Hepatocito/metabolismo , Compuestos Heterocíclicos/farmacología , Masculino , Ratas , Ratas Endogámicas Lew , Receptores CXCR4/antagonistas & inhibidores , Receptores CXCR4/metabolismo , Albúmina Sérica/análisis , Tacrolimus/farmacología , Resultado del TratamientoRESUMEN
BACKGROUND: Perforations and anastomotic leaks of the gastrointestinal tract are severe complications, which carry high morbidity and mortality and management of these is a multi-disciplinary challenge. The use of endoluminal vacuum (EVAC) therapy has recently proven to be a useful technique to manage these complications. We report our institution's experience with this novel technique in the chest, abdomen, and pelvis. METHODS: This is a retrospective review of an IRB approved registry of all EVAC therapy patients from July 2013 to December 2016. A total of 55 patients were examined and 49 patients were eligible for inclusion: 15 esophageal, 21 gastric, 3 small bowel, and 10 colorectal defects. The primary endpoint was closure rate of the GI tract defect with EVAC therapy. RESULTS: Fifteen (100%) esophageal defects closed with EVAC therapy. Mean duration of therapy was 27 days consisting of an average of 6 endosponge changes every 4.8 days. Eighteen (86%) gastric defects closed with EVAC therapy. Mean duration of therapy was 38 days with a mean of 9 endosponge changes every 5.3 days. Three (100%) small bowel defects closed with EVAC therapy. Mean duration of therapy was 13.7 days with a mean of 2.7 endosponge changes every 4.4 days. Six (60%) colorectal defects closed with EVAC therapy. Mean duration of therapy was 23.2 days, consisting of a mean of 6 endosponge changes every 4.0 days. There were two deaths, which were not directly related to EVAC therapy and occurred outside the measured 30-day mortality. CONCLUSION: Our experience demonstrates that EVAC therapy is feasible and effective for the management of gastrointestinal perforations/leaks throughout the GI tract and can be considered as a safe alternative to surgical intervention in select cases.
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Fuga Anastomótica/terapia , Enfermedades Gastrointestinales/terapia , Terapia de Presión Negativa para Heridas/métodos , Adulto , Anciano , Fuga Anastomótica/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , VacioRESUMEN
A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced-size (50%) Lewis rat livers are transplanted into green fluorescence protein transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol-fed Lewis hosts developed fibrosis, whereas no fibrosis was observed in control-fed recipients. Host-derived CD133 + 8-hydroxy-2'-deoxyguanosine (8-OHdG) cells were significantly increased in livers recovered from both alcohol-fed and control recipients, but only alcohol-fed recipients demonstrated co-staining (a marker of oxidative DNA damage). α smooth muscle actin (α-SMA) staining, a marker for myofibroblasts, also co-localized with CD133 + cells only in the livers of alcohol-fed recipients. Immunostaining and polymerase chain reaction analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells (BMSCs) expressing CD133, c-Kit, and chemokine (C-X-C motif) receptor 4 markers and caused oxidative mitochondria DNA (mtDNA) damage. Culture of CD133 + cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8-OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased α-SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in BMSCs of chronic alcohol-fed recipients, and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. Liver Transplantation 23 1564-1576 2017 AASLD.
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Insuficiencia Hepática Crónica Agudizada/cirugía , Aloinjertos/patología , Células de la Médula Ósea/efectos de los fármacos , Hepatitis Alcohólica/cirugía , Trasplante de Hígado/efectos adversos , Hígado/patología , Células Madre/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Insuficiencia Hepática Crónica Agudizada/etiología , Alcoholismo/complicaciones , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/patología , Daño del ADN/efectos de los fármacos , ADN Mitocondrial/genética , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animales de Enfermedad , Etanol/toxicidad , Fibrosis , Hepatitis Alcohólica/complicaciones , Humanos , Hígado/citología , Hígado/efectos de los fármacos , Trasplante de Hígado/métodos , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Miofibroblastos/efectos de los fármacos , Miofibroblastos/patología , Ratas , Ratas Endogámicas Lew , Células Madre/patología , Trasplante Isogénico/efectos adversos , Trasplante Isogénico/métodosRESUMEN
BACKGROUND AND AIMS: Direct pancreas juice testing of bicarbonate, lipase, or trypsin after stimulation by secretin or cholecystokinin is used to determine exocrine function, a surrogate for diagnosing chronic pancreatitis (CP). Endoscopic pancreas function tests (ePFTs), where a peak bicarbonate concentration (PBC) ≥80 mEq/L in pancreas juice is considered normal, are now used more frequently. In this ePFT, aspirates start 35 minutes after secretin administration because pancreas output peaks 30 minutes after secretagogue administration. The performance of ePFT in a cohort of patients with a presumptive diagnosis of CP referred to a pancreas clinic for consideration of an intervention including total pancreatectomy and islet autotransplantation was studied, compared with EUS, ERCP, histology, and consensus diagnosis. The effect of sedation, narcotic use, aspirate volume, body mass index, age, and proton pump inhibitors (PPIs) on test performance is reported. METHODS: After a test dose, synthetic human secretin was administered intravenously, and 30 minutes later sedation was achieved with midazolam and fentanyl or propofol. A gastroscope was advanced to the major papilla where 4 continuous aspiration samples were performed at 5-minute intervals in sealed bottles. PBC ≥80 mEq/L was normal. RESULTS: Eighty-one patients had ePFTs from August 2010 through October 2015. Twenty-seven patients (33%) were diagnosed with CP. Eighteen of the 27 patients with CP and 1 of the 54 patients without CP had an abnormal ePFT, producing a sensitivity of 66% (95% CI, 46.0-83.5), specificity 98% (95% CI, 90.1-99.9), positive predictive value 94.7% (95% CI, 74-99.9), and negative predictive value 85.5% (95% CI, 74.2-93.1). ERCP and PBC concordance was generally poor, but none of the patients without CP had major EUS changes, and only 3 patients with a PBC <80 mEq/L had a normal EUS. The PBC was affected by narcotics and PPI use. CONCLUSION: A 20-minute ePFT after secretin administration had a marginal sensitivity for diagnosis of CP. The diagnosis of CP should not rely on a single study and certainly not a PFT. The duodenal aspirate volume did not correlate with the PBC, which contrasts with current secretin-enhanced MRCP knowledge; therefore, further studies on this subject are warranted. Neither type of sedation, BMI, nor age affected test performance. Narcotics and PPIs may affect the PBC, so borderline results should be interpreted with caution in these groups.
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Endoscopía del Sistema Digestivo , Fármacos Gastrointestinales/administración & dosificación , Pruebas de Función Pancreática/métodos , Jugo Pancreático/química , Pancreatitis Crónica/diagnóstico , Secretina/administración & dosificación , Adulto , Factores de Edad , Bicarbonatos/metabolismo , Índice de Masa Corporal , Colangiopancreatografia Retrógrada Endoscópica , Endosonografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Narcóticos/farmacología , Jugo Pancreático/efectos de los fármacos , Jugo Pancreático/metabolismo , Pancreatitis Crónica/diagnóstico por imagen , Pancreatitis Crónica/patología , Valor Predictivo de las Pruebas , Inhibidores de la Bomba de Protones/farmacología , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Gastric variceal bleeding is associated with significant morbidity and mortality in patients with portal hypertension and cirrhosis. Options are limited for patients who are not candidates for transjugular intrahepatic portosystemic shunts (TIPS). Cyanoacrylate injections have been reported to be efficacious in previous case series. The aim of this retrospective study was to report our single-center experience with the safety and efficacy of 2-octyl-cyanoacrylate in patients who were not TIPS candidates. Electronic medical records were reviewed for 16 patients who underwent a total of 18 esophagogastroduodenoscopies for acute gastric or duodenal variceal bleeding and secondary prophylaxis of gastric varices; 14 patients had cirrhosis with an average Model for End-Stage Liver Disease score of 16, and 2 patients had noncirrhotic portal hypertension. Primary endpoints of the study included early and delayed rebleeding rate, complications, and death or liver transplantation. The rebleeding rate (early or delayed) was 7%, and no complications were found. One death was reported (unrelated to the procedure). In conclusion, 2-octyl-cyanoacrylate is a safe and effective alternative for non-TIPS candidates who present with acute gastric variceal bleeding given its low rebleeding and complication rate.