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1.
Clin Gastroenterol Hepatol ; 20(2): 293-302.e9, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33549868

RESUMO

BACKGROUND & AIMS: Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis who have undergone colectomy. Pouchitis has been considered a single entity despite a broad array of clinical and endoscopic patterns. We developed a novel classification system based on the pattern of inflammation observed in pouches and evaluated the contributing factors and prognosis of each phenotype. METHODS: We identified 426 patients (384 with ulcerative colitis) treated with proctocolectomy and IPAA who subsequently underwent pouchoscopies at the University of Chicago between June 1997 and December 2019. We retrospectively reviewed 1359 pouchoscopies and classified them into 7 main pouch phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted 6 months after ileostomy takedown. Logistic regression analysis was used to assess factors contributing to each phenotype. Pouch survival was estimated by the log-rank test and the Cox proportional hazards model. RESULTS: Significant contributing factors for afferent limb involvement were a body mass index of 25 or higher and hand-sewn anastomosis, for inlet involvement the significant contributing factor was male sex; for diffuse inflammation the significant contributing factors were extensive colitis and preoperative use of anti-tumor necrosis factor drugs, for cuffitis the significant contributing factors were stapled anastomosis and preoperative Clostridioides difficile infection. Inlet stenosis, diffuse inflammation, and cuffitis significantly increased the risk of pouch excision. Diffuse inflammation was associated independently with pouch excision (hazard ratio, 2.69; 95% CI, 1.34-5.41; P = .005). CONCLUSIONS: We describe 7 unique IPAA phenotypes with different contributing factors and outcomes, and propose a new classification system for pouch management and future interventional studies.


Assuntos
Colite Ulcerativa , Colite , Bolsas Cólicas , Doenças Inflamatórias Intestinais , Pouchite , Proctocolectomia Restauradora , Colite/complicações , Colite Ulcerativa/complicações , Bolsas Cólicas/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Fenótipo , Pouchite/etiologia , Proctocolectomia Restauradora/efeitos adversos , Estudos Retrospectivos
2.
Dig Dis Sci ; 67(8): 4020-4031, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35288827

RESUMO

BACKGROUND: The endoscopic appearance in patients with "pouchitis" after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can be quite heterogenous. Patients with an endoscopic phenotype resembling Crohn's disease (CD) are at high risk of pouch loss. AIMS: We aimed to assess how the histopathology of colectomy specimens predicts endoscopic pouch phenotypes in UC. METHODS: We retrospectively assessed pouchoscopies from patients with UC who underwent IPAA and classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted ≥ 6 months from ileostomy takedown. We assessed the clinical and pathological data including deep, focal inflammation, granulomas, and terminal ileal involvement in the colectomy specimens. Logistic regression analysis was performed to identify contributing factors to each phenotype. RESULTS: This study included 1,203 pouchoscopies from 382 patients with UC. On multivariable analysis, deep inflammation was significantly associated with pouch fistulas (Odds ratio 3.27; 95% confidence interval 1.65-6.47; P = 0.0007). Of the 75 patients with deep inflammation, only two patients (2.7%) were diagnosed with CD based on pathology review. Terminal ileal involvement significantly increased the risk of afferent limb involvement (Odds ratio 2.96; 95% confidence interval 1.04-8.47; P = 0.04). There were no significant associations between other microscopic features and phenotypes. CONCLUSIONS: We identify histologic features of colectomy specimens in UC that predict subsequent pouch phenotypes. Particularly, deep inflammation in the resected colon was significantly associated with pouch fistulas, a pouch phenotype with poor prognosis.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Doença de Crohn , Proctocolectomia Restauradora , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Bolsas Cólicas/patologia , Doença de Crohn/diagnóstico , Humanos , Inflamação/complicações , Fenótipo , Proctocolectomia Restauradora/efeitos adversos , Estudos Retrospectivos
3.
Molecules ; 27(9)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35566024

RESUMO

BACKGROUND: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing. METHODS: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol 'spiked' into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined. RESULTS: Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min-1, 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL-1 with a limit of detection in standard solutions at 4 µg mL-1 and in 'spiked' urine samples at 15 µg mL-1. The intra-assay and inter-assay CVs were between 2.0-5.1% and 2.0-5.1% for lactulose and 2.5-4.4% and 2.8-3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively. CONCLUSIONS: The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability.


Assuntos
Lactulose , Manitol , Cromatografia Líquida de Alta Pressão/métodos , Absorção Intestinal , Lactulose/urina , Manitol/urina , Permeabilidade , Reprodutibilidade dos Testes
4.
Immunol Cell Biol ; 99(4): 419-427, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33169881

RESUMO

Increased global industrialization has increased air pollution resulting in 3 million annual deaths globally. Air pollutants could have different health effects, so specific models to identify the different immune effects are needed. The aim of this study was to determine the immune effects and lung function of acute exposure to two different pollution sources using a mouse model. Three intranasal challenges with either urban dust or diesel particulate matter resulted in significant (P < 0.001) immune cell infiltration into the lung, which was mostly because of an increased (P < 0.001) percentage of neutrophils. We found that exposure to either urban dust or diesel particulate matter significantly increased the lung tissue concentration of the neutrophil chemoattractant cytokine CXCL5 when compared with naïve controls. The urban dust challenge also significantly increased the concentration of the proinflammatory cytokine CCL20, but diesel particulate matter did not. The urban dust challenge significantly (P < 0.001) decreased tissue compliance and ability to stretch, and increased total airways constriction and lung tissue stiffness. In comparison, diesel particulate matter exposure slightly, but significantly (P = 0.022), increased tissue compliance and did not affect other lung function parameters. Although both urban dust and diesel particulate matter induced immune cell infiltration into the lung resulting in lung inflammation, their detrimental effects on cytokine production and lung function were quite different. This may be attributed to the variation in particulates that comprise these pollutants that directly interact with the lung tissue and consequently elicit a different functional response.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poeira/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Emissões de Veículos/análise
5.
Digestion ; 102(5): 767-775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556932

RESUMO

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with disease activity in Crohn's disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. METHODS: CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6-12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. RESULTS: Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of <15, 15-30, and >30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; p = 0.028). On multivariate analysis, vitamin D >30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.66, p = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08-0.83, p = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (p = 0.17, 0.55, 0.062, respectively). CONCLUSION: In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.


Assuntos
Doença de Crohn , Deficiência de Vitamina D , Doença de Crohn/cirurgia , Humanos , Período Pós-Operatório , Recidiva , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia
6.
Ann Surg ; 272(1): 130-137, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-30720502

RESUMO

OBJECTIVE: Review the long-term outcomes of the side-to-side isoperistaltic strictureplasty (SSIS) and its effects on bowel preservation in Crohn disease (CD). SUMMARY BACKGROUND DATA: The first SSIS was performed 25 years ago as an alternative to resection in the treatment of extensive fibrostenosing jejuno-ileal CD. METHODS: Prospective study (January 1992-December 2016) of all patients with a SSIS performed by the authors. Long-term outcomes were evaluated radiographically, endoscopically, and histopathologically. RESULTS: Sixty patients [14.4% of patients with jejuno-ileal bowel CD; 31 females; median age 36 (12-69) years] underwent 61 SSIS's for partial intestinal obstruction. Median length of preserved small bowel was 50 (20-148) cm. Associated strictureplasties and bowel resection were performed in 44% and 80%, respectively. Postoperative mortality occurred in 1 (PE on POD#8) and postoperative morbidity in 7 (12%). There were no sutureline dehiscences. SSIS resulted in resolution of preoperative symptoms in all. After a median follow-up of 11 years (range 1 mo-25 yrs), symptomatic recurrence was observed in 61%: 15 patients at the SSIS and 19 away from it (2 cases unclear location; 7 patients with >1 recurrence). Of 15 recurrences at SSIS's, 11 required surgical treatment (revision or strictureplasty in 6, SSIS removal in 5). Fifty-one patients (86%) maintain the original SSIS to date. CONCLUSIONS: SSIS is a safe, effective, and durable strictureplasty in patients with extensive fibrostenosing CD of the small bowel. Half the surgical recurrences on SSIS can be managed by subsequent revision or strictureplasty. The majority of patients maintain the original SSIS after a median follow-up of 11 years.


Assuntos
Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Clin Gastroenterol Hepatol ; 17(1): 205-206, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29751167

RESUMO

The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1-3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.4-6 We hypothesized that if a lesion was completely removed surgically and followed up endoscopically, metachronous colorectal carcinoma would be a rare occurrence. Thus, segmental resection may be offered as a definitive surgery in patients with chronic colitis and localized colorectal neoplasia in whom endoscopic resection is not feasible. Retention of the distal colon/rectum is expected to result in an overall improved quality of life compared with permanent ileostomy or an ileoanal J-pouch. Here, we report our experience and follow-up evaluation of segmental resections for preoperative neoplasia in patients with Crohn's disease (CD) or ulcerative colitis (UC).


Assuntos
Colectomia/métodos , Colite/complicações , Neoplasias do Colo/cirurgia , Adulto , Idoso , Neoplasias do Colo/diagnóstico , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Dis Colon Rectum ; 62(11): 1344-1351, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31596761

RESUMO

BACKGROUND: Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity. OBJECTIVE: The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis. DESIGN: This is a retrospective case-control study. SETTINGS: This study was conducted at a tertiary-care IBD center. PATIENTS: Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included. MAIN OUTCOME MEASURES: The primary outcome measured was the incidence of pouchitis. RESULTS: Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes. LIMITATIONS: The retrospective design was a limitation of this study. CONCLUSION: In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.


Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Complicações Pós-Operatórias , Pouchite , Proctocolectomia Restauradora , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Estudos de Casos e Controles , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Illinois/epidemiologia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Pouchite/diagnóstico , Pouchite/epidemiologia , Pouchite/etiologia , Período Pré-Operatório , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Medição de Risco , Fatores de Risco
9.
Dis Colon Rectum ; 62(4): 463-469, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30540661

RESUMO

BACKGROUND: Anastomotic complications after restorative total proctocolectomy with IPAA for ulcerative colitis alter functional outcomes and quality of life and may lead to pouch failure. Routine contrast enema of the pouch assesses anastomotic integrity before ileostomy reversal, but its clinical use is challenged. OBJECTIVE: The purpose of this research was to assess the relationship among preoperative clinical characteristics, abnormal pouchography, and long-term pouch complications. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at a tertiary care center between 2000 and 2010. PATIENTS: Ulcerative colitis patients with IPAA undergoing pouchography before ileostomy closure were included. MAIN OUTCOME MEASURES: Patient demographics, incidence of pouch-related complications, and findings on pouchogram were recorded. Primary outcome was pouch failure, defined as excision or permanent diversion of the ileoanal pouch. Independent predictors of pouch failure were determined by multivariate regression. RESULTS: A total of 262 patients with ulcerative colitis were included. Contrast extravasation was seen in 27 patients (10.3%): 14 (51.9%) were clinically asymptomatic at the time of pouchogram. Six (22.2%) of 27 patients with extravasation developed pouch failure despite normalization of the pouchogram before ileostomy closure. Forty patients (15.3%) were found to have pouch-anal anastomotic stenosis; only 1 developed pouch failure. Pre-IPAA serum albumin and hemoglobin levels were inversely associated with contrast extravasation (serum albumin: OR = 0.42; hemoglobin: OR = 0.77; p < 0.05). Contrast extravasation was associated with delayed takedown operation (average = 67 d), increased risk (OR = 5.25; p < 0.01), and shorter time (median = 32.0 vs 72.5 mo; HR = 5.88; p < 0.05) to pouch failure, as well as increased risk of pouch-related complications (p < 0.05). LIMITATIONS: The study was limited by its retrospective nature and small number of patients who developed pouch failure. CONCLUSIONS: Pouchography before ileostomy takedown is useful in identifying patients with ulcerative colitis at risk for postoperative complications. Radiologic resolution of IPAA-related leak does not reliably predict healing; caution is warranted in this subgroup. See Video Abstract at http://links.lww.com/DCR/A818.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Complicações Pós-Operatórias , Proctocolectomia Restauradora , Qualidade de Vida , Radiografia Abdominal , Adulto , Colite Ulcerativa/epidemiologia , Meios de Contraste/farmacologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico , Feminino , Humanos , Ileostomia/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/psicologia , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Radiografia Abdominal/efeitos adversos , Radiografia Abdominal/métodos , Reoperação/métodos , Estudos Retrospectivos , Estados Unidos/epidemiologia
10.
J Gastroenterol Hepatol ; 34(12): 2090-2095, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31169926

RESUMO

BACKGROUND AND AIM: Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy. METHODS: Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed. RESULTS: A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy. CONCLUSIONS: Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Substituição de Medicamentos/métodos , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Doença de Crohn/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
11.
Am J Gastroenterol ; 112(9): 1423-1429, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28719595

RESUMO

OBJECTIVES: Vedolizumab is increasingly used to treat patients with ulcerative colitis (UC) and Crohn's disease (CD), however, its safety during the perioperative period remains unclear. We compared the 30-day postoperative complications among patients treated preoperatively with vedolizumab, anti-tumor necrosis factor (TNF)-α agents or non-biological therapy. METHODS: The retrospective study cohort was comprised of patients receiving vedolizumab, anti-TNF-α agents or non-biological therapy within 4 weeks of surgery. The rates of 30-day postoperative complications were compared between groups using univariate and multivariate analysis. Propensity score-matched analysis was performed to compare the outcome between groups. RESULTS: Among 443 patients (64 vedolizumab, 129 anti-TNF-α agents, and 250 non-biological therapy), a total of 144 patients experienced postoperative complications (32%). In multivariate analysis, age >65 (odds ratio (OR) 3.56, 95% confidence interval (CI) 1.30-9.76) and low-albumin (OR 2.26, 95% CI 1.28-4.00) were associated with increased risk of 30-day postoperative complications. For infectious complications, steroid use (OR 3.67, 95% CI 1.57-8.57, P=0.003) and low hemoglobin (OR 3.03, 95% CI 1.32-6.96, P=0.009) were associated with increased risk in multivariate analysis. Propensity score matched analysis demonstrated that the risks of postoperative complications were not different among patients preoperatively receiving vedolizumab, anti-TNF-α agents or non-biological therapy (UC, P=0.40; CD, P=0.35). CONCLUSIONS: In the present study, preoperative vedolizumab exposure did not affect the risk of 30-day postoperative complications in UC and CD. Further, larger studies are required to confirm our findings.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Inflamatórias Intestinais/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Illinois/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Pontuação de Propensão , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia
12.
Am J Physiol Lung Cell Mol Physiol ; 311(3): L628-38, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27371734

RESUMO

Lung fibrosis negatively impacts on lung function in chronic asthma and is linked to the development of profibrotic macrophage phenotypes. Epidemiological studies have found that lung function benefits from increased consumption of fruit high in polyphenols. We investigated the effect of boysenberry consumption, in both therapeutic and prophylactic treatment strategies in a mouse model of chronic antigen-induced airway inflammation. Boysenberry consumption reduced collagen deposition and ameliorated tissue remodeling alongside an increase in the presence of CD68+CD206+arginase+ alternatively activated macrophages in the lung tissue. The decrease in tissue remodeling was associated with increased expression of profibrolytic matrix metalloproteinase-9 protein in total lung tissue. We identified alternatively activated macrophages in the mice that consumed boysenberry as a source of the matrix metalloproteinase-9. Oral boysenberry treatment may moderate chronic tissue remodeling by supporting the development of profibrolytic alternatively activated macrophages expressing matrix metalloproteinase-9. Regular boysenberry consumption therefore has the potential to moderate chronic lung remodeling and fibrosis in asthma and other chronic pulmonary diseases.


Assuntos
Asma/dietoterapia , Frutas , Pulmão/patologia , Macrófagos Alveolares/imunologia , Rubus , Remodelação das Vias Aéreas , Animais , Asma/imunologia , Asma/fisiopatologia , Colágeno/metabolismo , Dieta , Pulmão/imunologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL
13.
Int J Mol Sci ; 17(11)2016 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-27845745

RESUMO

Allergic asthma is an inflammatory lung disease that is partly sustained by the chemokine eotaxin-3 (CCL26), which extends eosinophil migration into tissues long after allergen exposure. Modulation of CCL26 could represent a means to mitigate airway inflammation. Here we evaluated procyanidin A2 as a means of modulating CCL26 production and investigated interactions with the known inflammation modulator, Interferon γ (IFNγ). We used the human lung epithelial cell line A549 and optimized the conditions for inducing CCL26. Cells were exposed to a range of procyanidin A2 or IFNγ concentrations for varied lengths of time prior to an inflammatory insult of interleukin-4 (IL-4) for 24 h. An enzyme-linked immunosorbent assay was used to measure CCL26 production. Exposing cells to 5 µM procyanidin A2 (prior to IL-4) reduced CCL26 production by 35% compared with control. Greatest inhibition by procyanidin A2 was seen with a 2 h exposure prior to IL-4, whereas IFNγ inhibition was greatest at 24 h. Concomitant incubation of procyanidin A2 and IFNγ did not extend the inhibitory efficacy of procyanidin A2. These data provide evidence that procyanidin A2 can modulate IL-4-induced CCL26 production by A549 lung epithelial cells and that it does so in a manner that is different from IFNγ.


Assuntos
Catequina/farmacologia , Quimiocinas CC/biossíntese , Fatores Imunológicos/farmacologia , Interleucina-4/fisiologia , Proantocianidinas/farmacologia , Células A549 , Asma/tratamento farmacológico , Asma/imunologia , Quimiocina CCL26 , Quimiocinas CC/genética , Avaliação Pré-Clínica de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Expressão Gênica , Humanos , Alvéolos Pulmonares/citologia
14.
Int J Colorectal Dis ; 30(1): 87-95, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25376336

RESUMO

PURPOSE: Perineal wounds after complete proctectomy are at risk for failure, with dramatic consequences on patients' health and quality of life. This study is aimed at identifying risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy. METHODS: Data from 284 patients undergoing total proctectomy from 2002 to 2012 either at the University of Chicago Medical Center or the Catholic University of Rome Hospital were collected and analyzed. RESULTS: Overall, the perineal wound complication rate was 21.8%. Successful conservative management was accomplished in 45.2% of cases. Complications occurred significantly more often in patients with a higher Charlson score index, with the diagnosis of rectal cancer, who had received preoperative radiation and who had a surgical drain placed at the time of initial surgery. Neoadjuvant radiation was the only significant risk factor at multivariate analysis (OR 4.40). In the rectal cancer subgroup, younger age, female gender, and preoperative radiation were predictors of wound complications. Based on that, a 3-point score (radiation, age, and gender (RAG)) was developed. Patients with a score of 3 had a 50% risk of developing a perineal wound complication. CONCLUSIONS: Perineal wound complications are a common and burdensome problem after total proctectomy. Preoperative radiation is the single most significant and controllable risk factor predicting perineal wound failure. In the presence of multiple, non-modifiable risk factors, alternative approaches to primary closure should be considered in managing complex perineal defects.


Assuntos
Períneo/cirurgia , Complicações Pós-Operatórias , Neoplasias Retais/cirurgia , Reto/cirurgia , Abscesso/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Períneo/fisiopatologia , Cuidados Pré-Operatórios/efeitos adversos , Qualidade de Vida , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/etiologia , Úlcera/etiologia , Cicatrização
15.
World J Surg ; 38(4): 976-84, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24240673

RESUMO

BACKGROUND: Portomesenteric venous thrombosis (PVT) is a known complication after open and laparoscopic colorectal (LCR) surgery. Risk factors and the prognosis of PVT have been poorly described. METHODS: This study is a retrospective analysis of a prospectively collected database. Patients with new-onset postoperative abdominal pain were evaluated with a computed tomography scan of the abdomen. Patients found to have PVT were analyzed. A multivariate analysis was performed to identify predictors of PVT. RESULTS: A total of 1,069 patients undergoing LCR surgery for inflammatory bowel disease (IBD) or nonmetastatic cancer between June 2002 and June 2012 were included. Altogether, 37 (3.5 %) patients experienced symptomatic postoperative PVT. On univariate analysis, IBD (p < 0.001), ulcerative colitis (p = 0.016), preoperative therapy with steroids (p = 0.008), operative time ≥220 min (p = 0.004), total proctocolectomy (TPC) (p < 0.001), ileoanal pouch anastomosis (p = 0.006), and postoperative intraabdominal septic complications (p < 0.001) were found to be significant risk factors. By multivariate analysis, TPC (p = 0.026) and postoperative intraabdominal septic complications (p < 0.001) were independent predictors of PVT. In the PVT group, postoperative length of stay was longer (14.8 vs. 7.4 days, p < 0.001). Of the patients evaluated with a hematologic workup, 72.7 % were found to have a hypercoagulable condition. All patients were managed with oral anticoagulation for at least 6 months. No death or complications related to PVT occurred. CONCLUSIONS: PVT is a potentially serious complication that is more likely to occur after TPC and in the presence of postoperative intraabdominal septic complications, particularly in patients with a coagulation disorder. Prompt diagnosis and treatment with oral anticoagulation are recommended to avoid long-term sequelae.


Assuntos
Colectomia , Laparoscopia , Oclusão Vascular Mesentérica/etiologia , Veia Porta , Complicações Pós-Operatórias/etiologia , Reto/cirurgia , Trombose Venosa/etiologia , Adulto , Colectomia/métodos , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Doenças Inflamatórias Intestinais/cirurgia , Masculino , Oclusão Vascular Mesentérica/epidemiologia , Veias Mesentéricas , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Proctocolectomia Restauradora , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/epidemiologia
16.
Clin Exp Pharmacol Physiol ; 41(2): 107-17, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24033480

RESUMO

The effects of inflammatory changes on the absorption of different-sized probes and their permeability ratios are poorly understood. The aim of the present study was to determine the effects of a pharmacological agent on the permeability of the gut mucosa to saccharidic probes of larger and smaller molecular weight. Permeability was assessed by half-hourly urinary excretion of a combined dose of d-mannitol, l-rhamnose and lactulose following consumption of a single 600 mg dose of aspirin and compared with a placebo in a cross-over study in 20 healthy female volunteers. The temporal patterns of excretion of all probes were bimodal, being best fitted by polynomial functions. The relatively small early peak was evident for at least 4 h for smaller sugars, but was less evident with lactulose, being overshadowed by a larger second peak. These conclusions were further supported by separate analyses of the segments of the temporal plots between 2.5 and 4 h and between 4.5 and 6 h. The forms of these curves did not change significantly following dosing with aspirin. A greater proportion of the total dose of mannitol than rhamnose was excreted over the collection period. Following the consumption of aspirin, the cumulative rate of excretion of the smaller sugars (i.e. mannitol and rhamnose) was significantly reduced whereas that of lactulose was increased over the 6 h collection period. Aspirin has opposite effects on the absorption of larger and smaller probes, influencing the outcome of the test. These results have important consequences for the design and comparison of clinical tests of permeability.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Carboidratos/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Adulto , Carboidratos/urina , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Mucosa Intestinal/metabolismo , Lactulose/farmacocinética , Lactulose/urina , Manitol/farmacocinética , Manitol/urina , Permeabilidade , Ramnose/farmacocinética , Ramnose/urina , Sensibilidade e Especificidade , Urina/química , Adulto Jovem
17.
Am J Surg ; 233: 29-36, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38365552

RESUMO

INTRODUCTION: Concerns have been voiced regarding the possibility of health risks to the operating room personnel from exposure to surgical smoke generated from electrocautery. METHODS: Ovid Medline was queried using search terms "surgical smoke", "electrosurgery," "smoke evacuator". The NIOSH Health Hazard Evaluations Database was searched using terms, "hospital", "operating room", "Ames", "mutagen", and "salmonella". RESULTS: Levels of pollutants in the breathable airspace within the operating room have been repeatedly shown to be very low. Absolute counts of particulate matter in the operating room are low when compared to other environments. The possibility for virus transmission with electrocautery in the operating room is unknown. CONCLUSIONS: The risks related to the exposure to electrocautery surgical smoke have been overstated. Rigid mandates requiring smoke evacuators in all situations are not justified at this time.


Assuntos
Eletrocoagulação , Exposição Ocupacional , Salas Cirúrgicas , Fumaça , Fumaça/análise , Humanos , Eletrocoagulação/efeitos adversos , Exposição Ocupacional/prevenção & controle , Estados Unidos
18.
Inflamm Bowel Dis ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916136

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time. METHODS: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype. RESULTS: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15). CONCLUSIONS: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome.


Endoscopic pouch phenotypes can change over time and subsequent development of diffuse inflammation, pouch-related fistulas, and afferent limb/inlet stenoses significantly worsen pouch outcomes. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcomes.

19.
Dis Colon Rectum ; 56(4): 449-57, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23478612

RESUMO

BACKGROUND: The impact of infliximab on the postoperative course of patients with IBD is under debate. OBJECTIVE: The aim of this study was to evaluate the influence of infliximab on perioperative outcomes in patients undergoing elective laparoscopic resection for IBD. DESIGN: This study is a retrospective analysis of a prospectively collected, institutional review board-approved database. SETTING, PATIENTS, INTERVENTIONS: Patients undergoing laparoscopic resection on preoperative infliximab (infliximab group) were compared with patients who did not receive infliximab (noninfliximab group). MAIN OUTCOME MEASURES: The short-term and long-term morbidity and mortality rates were assessed. RESULTS: Elective laparoscopic resection for IBD was performed on 518 patients from January 2004 through June 2011; 142 patients were treated with infliximab preoperatively. Both groups had similar demographics, type and severity of IBD, comorbidities, and type of surgery. A significantly higher number of patients in the infliximab group had been on aggressive medical therapy to control symptoms of IBD during the month preceding surgery, including steroids (73.9 vs 58.8%, p = 0.002) and immunosuppressors (32.4 vs 20.5%, p = 0.006). Operative time and blood loss were similar (p = 0.50 and p = 0.34). Intraoperative complication rate was 2.1% in both groups. No significant differences were observed in terms of the conversion rate to laparotomy (6.3% vs 9.3%, p = 0.36), overall 30-day postoperative morbidity (p = 0.93), or mortality (p = 0.61). The rates of anastomotic leak (2.1% vs 1.3%, p = 0.81), infections (12% vs 11.2%, p = 0.92), and thrombotic complications (3.5% vs 5.6%, p = 0.46) were similar. Subgroup analyses confirmed similar rates of overall, infectious, and thrombotic complications regardless of whether patients had ulcerative colitis or Crohn's disease. LIMITATIONS: This study is subject to the limitations of a retrospective design. CONCLUSIONS: Infliximab is not associated with increased rates of postoperative complications after laparoscopic resection.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Infliximab , Laparoscopia , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Duração da Cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Reoperação/estatística & dados numéricos , Estudos Retrospectivos
20.
J Gastrointest Surg ; 27(2): 382-389, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36400903

RESUMO

BACKGROUND: Surgeons are often asked to provide a diverting colostomy to enable healing or simplify management of sacral pressure ulcers. However, little evidence exists regarding the safety of a diversion in this often compromised patient population. We hypothesized that malnourished patients with sacral pressure ulcers have poor outcomes with fecal diversion. METHODS: ACS-NSQIP (2012-2018) was used to identify patients who underwent elective diverting colostomy for sacral pressure ulcers. Demographics, comorbidities, and perioperative details were recorded. Postoperative complications and 30-day mortality were compared between patients with moderate/severe hypoalbuminemia (< 2.5 g/dL) vs those with albumin > 2.5 g/dL. RESULTS: We identified a total of 863 patients who underwent elective diverting colostomy for sacral pressure ulcer. Mean age was 57.5 years old. Rate of associated comorbidities was high, with most patients classified as ASA class 3 or 4. Over 40% of patients had a preoperative albumin level < 2.5 g/dL. Thirty-day overall postoperative mortality was 6.7%. This was significantly higher in patients with hypoalbuminemia (11.4% vs. 3.5%, p < 0.001). On multivariable regression analysis, preoperative albumin < 2.5 g/dL was independently associated with mortality (OR 1.92, p = 0.039). Other factors associated with mortality included increased age (OR 1.04 per year, p < 0.001), preoperative sepsis (OR 1.66, p = 0.003), and Black race (OR 2.2, p = 0.01). CONCLUSIONS: Diverting colostomy performed for patients with sacral pressure ulcers is associated with a substantial risk of postoperative death. Surgeons should carefully consider risks of diversion in this patient population, especially in malnourished patients with hypoalbuminemia.


Assuntos
Hipoalbuminemia , Desnutrição , Úlcera por Pressão , Humanos , Pessoa de Meia-Idade , Úlcera por Pressão/cirurgia , Úlcera por Pressão/complicações , Colostomia , Hipoalbuminemia/complicações , Estudos Retrospectivos , Albuminas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Desnutrição/complicações , Fatores de Risco
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