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BACKGROUND & AIMS: The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn's disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification. METHODS: After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn's Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines. RESULTS: In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33-0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26-0.96), and severe ER (RR, 0.41; 95% CI, 0.21-0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups. CONCLUSIONS: Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/prevenção & controle , Doença de Crohn/cirurgia , Inibidores do Fator de Necrose Tumoral , Recidiva Local de Neoplasia , Fator de Necrose Tumoral alfa/uso terapêutico , Período Pós-Operatório , Recidiva , Imunossupressores/uso terapêuticoRESUMO
GOAL: The goal of this study was to describe medication utilization patterns in older inflammatory bowel disease (IBD) patients. BACKGROUND: Despite a growing population of older patients with Crohn's disease (CD) and ulcerative colitis (UC), questions remain regarding medication utilization patterns in comparison to younger populations. MATERIALS AND METHODS: We collected data from the 34 sites in TARGET-IBD, a multicenter, observational cohort. The primary outcome in this study was the IBD-specific therapy utilized among older patients with IBD compared with younger age groups. Therapy use was analyzed using pairwise comparisons and then the odds of IBD-specific therapy use among patients older than age 65 were evaluated using multivariable logistic regression models. RESULTS: We identified 2980 patients with IBD (61% CD). In multivariable analysis, younger patients with UC were significantly less likely to utilize aminosalicylate monotherapy when compared with patients above 65 years [age 18 to 29: adjusted odds ratio (aOR)=0.51, 95% confidence interval (CI): 0.33-0.78]. In patients with CD, younger patients were significantly less likely to use aminosalicylate monotherapy when compared with patients above 65 (greatest difference age 18 to 29: aOR=0.31, 95% CI: 0.18-0.52). Younger patients with CD and UC were significantly more likely to use anti-tumor necrosis factor monotherapy than patients above 65 years (age 18 to 29: aOR=3.87, 95% CI: 2.47-6.06 and aOR=2.68, 95% CI: 1.29-5.58, respectively). CONCLUSIONS: Older patients with IBD demonstrate significant differences in medication utilization, including more aminosalicylate monotherapy and less anti-tumor necrosis factor monotherapy compared with younger age groups. Given the aging population in the United States, these utilization patterns may have long-term implications for disease control.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Idoso , Doença Crônica , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Razão de Chances , Fator de Necrose Tumoral alfa , Estados Unidos , Adulto JovemRESUMO
PURPOSE OF REVIEW: This review aims to summarize the current evidence regarding the risks and implications of coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD) and discuss optimal management of IBD during this pandemic. RECENT FINDINGS: Patients with IBD are not at increased risk of COVID-19 but several risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection) have been identified, such as active IBD, obesity, and corticosteroid use. COVID-19 outcomes are similar among patients with IBD and the overall population. Although biologics have not been shown to increase the risk of severe COVID-19 complications, several risk factors have been associated with negative COVID-19 outcomes in patients with IBD, including older age, obesity, the presence of comorbidities, active disease, and corticosteroid use. IBD therapy should, therefore, be continued with the aim of attaining or maintaining remission, except for corticosteroids, which should be held or reduced to the minimal effective dose. Although it has been recommended that immunosuppressive therapy be held during a case of COVID-19, the half-lives of these drugs and data on the timing of restarting therapy limit the strength of these recommendations. We recommend COVID-19 vaccination for IBD patients whenever available, as benefits to the individual and to society outweigh the risks. SUMMARY: As our understanding of SARS-CoV-2 and COVID-19 continues to evolve, we are learning more about its impact in patients with IBD and how to better manage patients in this setting. Managing IBD during this pandemic has also highlighted the importance of restructuring services in order to adapt to current and potential future outbreaks. The COVID-19 pandemic has transformed IBD care through the expansion of telemedicine and development of novel approaches to remote monitoring.
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Produtos Biológicos/uso terapêutico , COVID-19/epidemiologia , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pandemias , Comorbidade , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Fatores de Risco , SARS-CoV-2RESUMO
BACKGROUND: MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn's disease (CD) recurrence and could be considered an additional biomarker of recurrence severity. METHODS: We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1. RESULTS: A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P<0.0001) and hypoglycosylated/abnormal (P<0.0001) forms in patients with severe endoscopic CD recurrence (i3+i4), ileal score i2, compared with patients in endoscopic remission (i0+i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score. CONCLUSIONS: MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.
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Doença de Crohn , Mucina-1/genética , Colo , Colonoscopia , Doença de Crohn/cirurgia , Humanos , Mucinas , Recidiva , Estudos Retrospectivos , Inibidores do Fator de Necrose TumoralRESUMO
BACKGROUND: Suicidal ideation (SI) is understudied in inflammatory bowel diseases (IBD). We aim to determine SI rates among IBD outpatients and to evaluate predictors of SI. MATERIALS AND METHODS: This is a prospective observational study of consecutive adult IBD outpatients over 18 months. Patients were screened for depression and SI using patient health questionnaire (PHQ-9). Demographic data were obtained from electronic medical record. Regression modeling was used for predictor analyses. RESULTS: In total, 71 of consecutive 1352 IBD outpatients had SI. Significant correlations between SI and depression severity, tricyclic antidepressants (TCA), IBD-related quality of life, and low vitamin D levels were seen. Univariate regression showed that depression severity, TCA use, and quality of life predicted SI. Multivariate regression showed depression severity (ß=0.46; P=0.002) and TCA use (ß=0.31; P=0.012) made unique contributions. CONCLUSIONS: SI is associated with depressive severity and less directly with IBD activity. Low-dose TCA, often used for chronic abdominal pain, is also a risk factor. Identifying the subset of IBD patients most vulnerable to SI can facilitate proper referrals to behavioral services and prevent progression to completed suicides.
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Depressão/epidemiologia , Doenças Inflamatórias Intestinais/psicologia , Qualidade de Vida , Ideação Suicida , Dor Abdominal/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos Tricíclicos/administração & dosagem , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
Since the publication of these Guidelines, the authors have noticed an error in the text on page 15. The incorrect statement is.
RESUMO
Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health-care providers should incorporate this guideline along with patient's needs, desires, and their values in order to fully and appropriately care for patients with Crohn's disease. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.
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Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/terapia , Fármacos Gastrointestinais/uso terapêutico , Fístula Intestinal/etiologia , Adalimumab/uso terapêutico , Corticosteroides/uso terapêutico , Certolizumab Pegol/uso terapêutico , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Progressão da Doença , Endoscopia Gastrointestinal , Fezes/química , Humanos , Fatores Imunológicos/uso terapêutico , Infliximab/uso terapêutico , Complexo Antígeno L1 Leucocitário/análise , Imageamento por Ressonância Magnética , Quimioterapia de Manutenção , Mesalamina/uso terapêutico , Avaliação de Sintomas , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. DESIGN: Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. RESULTS: 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. CONCLUSIONS: Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC.
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Apendicectomia/estatística & dados numéricos , Colectomia/estatística & dados numéricos , Colite Ulcerativa/cirurgia , Adolescente , Adulto , Colite Ulcerativa/diagnóstico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fumar , Fatores de Tempo , Adulto JovemRESUMO
Patients with chronic medically complex disorders like inflammatory bowel diseases (BD) often have mental health and psychosocial comorbid conditions. There is growing recognition that factors other than disease pathophysiology impact patients' health and wellbeing. Provision of care that encompasses medical care plus psychosocial, environmental and behavioral interventions to improve health has been termed "whole person care" and may result in achieving highest health value. There now are multiple methods to survey patients and stratify their psychosocial, mental health and environmental risk. Such survey methods are applicable to all types of IBD programs including those at academic medical centers, independent health systems and those based within independent community practice. Once a practice determines that a patient has psychosocial needs, a variety of resources are available for referral or co-management as outlined in this paper. Included in this white paper are examples of psychosocial care that is integrated into IBD practices plus innovative methods that provide remote patient management.
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Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/terapia , Psicologia , Humanos , Qualidade de VidaRESUMO
The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmune-associated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmune-related disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings. Although anti-enterocyte antibodies were identified in the majority of the cases, their presence was variable and insensitive. In addition, pediatric autoimmune enteropathy was frequently encountered in the setting of immunodeficiency disorders.
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Autoanticorpos/análise , Autoimunidade , Trato Gastrointestinal/imunologia , Síndromes de Imunodeficiência/imunologia , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Autoimunidade/efeitos dos fármacos , Biópsia , Criança , Pré-Escolar , Diarreia/imunologia , Enterócitos/imunologia , Enterócitos/patologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/patologia , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Masculino , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/mortalidade , Poliendocrinopatias Autoimunes/patologia , Valor Preditivo dos Testes , Sepse/imunologia , Resultado do TratamentoRESUMO
BACKGROUND: Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). METHODS: We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. RESULTS: Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). CONCLUSION: Development of EIPD was not associated with number or type of preoperative advanced therapies.
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Colite Ulcerativa , Bolsas Cólicas , Pouchite , Proctocolectomia Restauradora , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Bolsas Cólicas/efeitos adversos , Pouchite/complicações , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Inflamação/complicaçõesRESUMO
BACKGROUND: Neuromuscular fatigue is a common complaint in Crohn's disease (CD) patients. A correlation between serum vitamin D concentrations and neuromuscular function has been found in the elderly or non-ambulant populations. AIMS: The aim of this study was to determine whether CD patients exhibit impaired neuromuscular function and if so, is there a link between vitamin D and neuromuscular function. METHODS: Crohn's disease patients (n = 19) with at least one prior small bowel resection and matched controls (n = 19) underwent muscle strength and endurance testing, vitamin D, and nerve function analysis. RESULTS: Knee extension and flexion peak torque (Nm/kg) were greater in the control group than in the CD patients (P = 0.04 and 0.014, respectively. A significant difference was found between fatigue rates of the rectus femoris (P = 0.015) between CD patients and controls, but no difference was found in serum vitamin D levels between groups (P = 0.317). Knee extension and flexion torque measurements, with age as a covariate, were compared with high and low vitamin D levels. Those subjects with high serum vitamin D levels had a significantly greater extension peak torque (P = 0.045) and extension average torque (Nm/kg) (P = 0.014) than those with low levels. CONCLUSION: Crohn's disease patients with sufficient vitamin D levels experienced a 43 % greater extension peak torque. Although vitamin D deficiency has been associated with neuromuscular dysfunction, there were no differences in serum vitamin D levels between the CD and healthy controls to explain the decreased muscle strength.
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Doença de Crohn/complicações , Doença de Crohn/fisiopatologia , Doenças Neuromusculares/etiologia , Doenças Neuromusculares/fisiopatologia , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/fisiopatologia , Adulto , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Contração Isométrica/fisiologia , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Caminhada/fisiologiaRESUMO
BACKGROUND: Crohn's disease requires effective patient-clinician communication for successful illness and medication management. Shared decision making (SDM) has been suggested to improve communication around early intensive therapy. However, effective evidence-based SDM interventions for Crohn's disease are lacking, and the impact of SDM on Crohn's disease decision making and choice of therapy is unclear. AIM: To test the impact of SDM on choice of therapy, quality of the decision and provider trust compared to standard Crohn's disease care. METHODS: We conducted a multi-site cluster randomised controlled trial in 14 diverse gastroenterology practices in the US. RESULTS: A total of 158 adult patients with Crohn's disease within 15 years of their diagnosis, with no prior Crohn's disease complications, and who were candidates to receive immunomodulators or biologics, participated in the study. Among these, 99 received the intervention and 59 received standard care. Demographics were similar between groups, although there were more women assigned to standard care, and a slightly shorter disease duration among those in the intervention group. Participants in the intervention group more frequently chose combination therapy (25% versus 5% control, p < 0.001), had a significantly lower decisional conflict (p < 0.05) and had greater trust in their provider (p < 0.05). CONCLUSIONS: With rapidly expanding medication choices for Crohn's disease and slow uptake of early intensive therapy, SDM can personalise treatment strategies and has the potential to move the field of Crohn's disease management forward with an ultimate goal of consistently treating this disease early and intensively in appropriate patients. TRIAL REGISTRATION: Evaluating a Shared Decision Making Program for Crohn's Disease, ClinicalTrials.gov Identifier NCT02084290 https://clinicaltrials.gov/ct2/show/NCT02084290.
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Doença de Crohn , Adulto , Humanos , Feminino , Doença de Crohn/tratamento farmacológico , Tomada de Decisão Compartilhada , Tomada de DecisõesRESUMO
BACKGROUND: There are limited data on the postoperative outcomes in Crohn's disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesised that preoperative biologic use in Crohn's disease is not associated with postoperative complications after ileocolic resection. METHODS: Crohn's disease patients who underwent ileocolic resection over 2009-2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks of surgery was categorised as no biologic, anti-tumour necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. RESULTS: A total of 815 Crohn's disease patients who underwent an ileocolic resection were included [62% no biologic, 31.4% anti-tumour necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab]. Primary anastomosis was performed in 85.9% of patients [side-to-side 48.8%, end-to-side 26%, end-to-end 25%] in primarily a stapled [77.2%] manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modelling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumour necrosis factor [pâ =â 0.21], vedolizumab [pâ =â 0.17], or ustekinumab [pâ =â 0.52] was not significantly associated with intra-abdominal septic complication. Preoperative albuminâ <â 3.5 g/dl was independently associated with intra-abdominal septic complication (odds ratio [OR] 1.76 [1.03, 3.01]). CONCLUSIONS: In Crohn's disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery.
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Doença de Crohn/cirurgia , Hipoalbuminemia/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/uso terapêuticoRESUMO
Inflammatory bowel disease (IBD), a relatively common chronic debilitating intestinal illness, is composed of two broadly defined groups, Crohn's disease (CD) and ulcerative colitis (UC). Although several susceptibility genes for CD have been recently described, susceptibility genes exclusive for UC have not been forthcoming. Here, we show that receptor protein-tyrosine phosphatase sigma (PTPRS-encoding PTPsigma) knockout mice spontaneously develop mild colitis that becomes severe when challenged with two known inducers of colitis. We also demonstrate that E-cadherin and beta-catenin, two important adherens junction proteins involved in maintenance of barrier defense in the colon, act as colonic substrates for PTPsigma. Furthermore, we show that three SNPs (rs886936, rs17130, and rs8100586) that flank exon 8 in the human PTPRS gene are associated with UC. The presence of these SNPs is associated with novel splicing that removes the third immunoglobulin-like domain (exon 9) from the extracellular portion of PTPsigma, possibly altering dimerization or ligand recognition. We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis.