RESUMEN
BACKGROUND: A treat-to-target strategy for inflammatory bowel disease (IBD) recommends iterative treatment adjustments to achieve clinical and endoscopic remission. In asymptomatic patients with ongoing endoscopic activity, the risk/benefit balance of this approach is unclear, particularly with prior exposure to advanced therapies. METHODS: Using the RAND/UCLA Appropriateness Method, 9 IBD specialists rated appropriateness of changing therapy in 126 scenarios of asymptomatic patients with ulcerative colitis (UC) and Crohn's disease (CD) and active endoscopic disease. Disease extent and behavior, prior treatment, prior complications, and recent disease progression were considered, as were factors that might influence decision-making, including age and pregnancy. Ratings were collected via anonymous survey, discussed at an in-person meeting, and finalized in a second anonymous survey. RESULTS: Panelists rated change in therapy as appropriate (i.e., expected benefit sufficiently outweighs potential harms from continuing therapy) in 96/126 scenarios, generally in patients with progressive, complicated, and/or extensive disease, while changing therapy was rated uncertain in 27 scenarios of mild and/or stable disease. Changing therapy was rated inappropriate in UC patients with mild and stable disease previously exposed to ≥3 therapies or with improved endoscopic activity, and in CD patients with only scattered aphthous ulcers. The validated threshold for disagreement was not crossed for any scenario. Patient age >65 years and a plan for pregnancy in the next year might influence decision-making in some settings. CONCLUSION: Appropriateness ratings can help guide clinical decision-making about changing therapy to achieve endoscopic remission in asymptomatic patients with IBD until data from ongoing randomized studies are available.
RESUMEN
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%; Pâ =â .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.
RESUMEN
BACKGROUND: Clinical trial recruitment for patients with inflammatory bowel disease (IBD) has become more challenging over time. We aimed to develop recommendations for broadening IBD clinical trial eligibility to improve the inclusion of a more representative patient population in a more efficient timeline. METHODS: We applied the RAND/UCLA Appropriateness Method focused on broadening IBD clinical trial eligibility. A literature review was performed for 7 domains, each representing a different area related to trial recruitment. Based on these domains, 32 statements were developed. A questionnaire was sent to IBD specialists to anonymously vote on each statement with regards to its appropriateness and feasibility. After the first round of voting, participants met for a moderated discussion to review all statements. At the end of the discussion a second round of anonymous voting led to the final recommendations. RESULTS: The final round of voting resulted in 26 statements. All were rated as feasible and 25 of 26 rated as appropriate. Recommendations generally are to be more inclusive of complicated disease phenotypes, more liberal around safety criteria, to recognize the importance of non-invasive imaging and biomarkers, to minimize the washout period and to not enforce a minimum or maximum number of prior medications, to allow a recently recorded colonoscopy to count as a baseline study, and to be less restrictive of age. CONCLUSION: Recommendations to broaden clinical trial eligibility were found to be both appropriate and feasible with a high degree of agreement amongst an international group of IBD specialists.
RESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.
Asunto(s)
NADP Transhidrogenasa AB-Específica , Riñón Poliquístico Autosómico Dominante , Canales Catiónicos TRPP , Humanos , Animales , Ratones , Modelos Animales de Enfermedad , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPP/metabolismo , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/patología , Riñón Poliquístico Autosómico Dominante/terapia , Riñón/patología , Riñón/fisiología , NADP Transhidrogenasa AB-Específica/metabolismo , Proteínas Mitocondriales/metabolismoRESUMEN
INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.
Asunto(s)
Productos Biológicos , Colitis Ulcerosa , Cuidados Posteriores , Productos Biológicos/uso terapéutico , Colitis Ulcerosa/patología , Hospitales , Humanos , Metilprednisolona/uso terapéutico , Alta del Paciente , Inhibidores del Factor de Necrosis TumoralRESUMEN
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.
Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Enfermedad de Crohn , Proctocolectomía Restauradora , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/cirugía , Reservorios Cólicos/patología , Enfermedad de Crohn/diagnóstico , Humanos , Inflamación/complicaciones , Fenotipo , Proctocolectomía Restauradora/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test. RESULTS: We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05). CONCLUSIONS: There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults.
Ileal pouchanal anastomosis is the most common surgical approach for patients with ulcerative colitis undergoing total proctocolectomy. Outcomes are informed by heterogeneous adult data cohorts often predating anti-tumor necrosis factor uptake. We find that for children in the modern era pouch loss occurs at higher rates.
Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Proctocolectomía Restauradora , Adulto , Anastomosis Quirúrgica , Niño , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/etiología , Colitis Ulcerosa/cirugía , Humanos , Complicaciones Posoperatorias/etiología , Proctocolectomía Restauradora/efectos adversos , Estudios Retrospectivos , Inhibidores del Factor de Necrosis TumoralAsunto(s)
Colitis Ulcerosa/fisiopatología , Recto/fisiopatología , Adulto , Anciano , Estudios de Casos y Controles , Colitis Ulcerosa/diagnóstico , Adaptabilidad , Femenino , Estado Funcional , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Presión , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
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.
Asunto(s)
Colitis Ulcerosa , Colitis , Reservorios Cólicos , Enfermedades Inflamatorias del Intestino , Reservoritis , Proctocolectomía Restauradora , Colitis/complicaciones , Colitis Ulcerosa/complicaciones , Reservorios Cólicos/efectos adversos , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Masculino , Fenotipo , Reservoritis/etiología , Proctocolectomía Restauradora/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Complete histologic normalization is associated with improved clinical outcomes in ulcerative colitis (UC). However, it is currently unknown what effect achieving histologic normalization has on the development of dysplasia. METHODS: We performed a retrospective analysis of 495 patients with a confirmed diagnosis of UC from a tertiary center. Patients were categorized according to the best histologic assessment they had during their disease course: histologic normalization, histologic quiescence, or persistent histologic activity. We assessed dysplasia rates in these patient groups after achieving histologic normalization or histologic quiescence, or 8 years after UC diagnosis in those with persistent histologic activity. Kaplan-Meier graphs and Cox regression analyses were performed to estimate this effect. RESULTS: The incidence rate of dysplasia development after achieving histologic normalization was statistically significantly less when compared with the incidence rate after achieving histologic quiescence (Pâ =â 0.001) and in those with persistent histologic activity 8 years after UC diagnosis (Pâ =â 0.033). In multivariate analysis, at any point throughout UC duration, dysplasia development was statistically lower in those with histologic normalization (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.13-0.81) but not in those with histologic quiescence (aHR, 0.52; 95% CI, 0.25-1.10), compared with those with persistent histologic inflammation. When assessing the time after achieving histologic normalization, histologic quiescence, or 8 years post UC diagnosis in those with persistent histologic activity, we found that patients with histologic normalization had a subsequent decreased risk of developing dysplasia (aHR, 0.09; 95% CI, 0.01-0.72), compared with patients without normalization. CONCLUSIONS: Histologic normalization is associated with a decreased risk in patients with UC of developing subsequent dysplasia, compared with patients without histologic normalization. These findings have implications for surveillance intervals.
Asunto(s)
Colitis Ulcerosa , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/patología , Colonoscopía , Humanos , Hiperplasia/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: It remains unknown whether ambulation or sleep predicts postoperative length of stay for patients with IBD. We aim to identify the utility of wearable biosensors in predicting postoperative length of stay for patients with IBD. METHODS: Associations of postoperative length of stay with step count/sleep duration/sleep efficiency measured by wearable biosensors were examined. The best-fitting multivariable linear regression model predicting length of stay was constructed using stepwise model selection. RESULTS: Final sample included 37 patients. Shorter sleep duration on postoperative day 4 (r = 0.51, p = 0.043) or 5 (r = 0.81, p = 0.0045) or higher sleep efficiency on postoperative day 5 (r = - 0.77, p = 0.0098) was associated with a shorter length of stay. Additionally, a more positive change in sleep efficiency from postoperative day 4-5 was associated with a shorter length of stay (r = - 0.77, p = 0.024). The best-fitting multivariable linear regression model revealed Clavien-Dindo grade 1 (p = 0.045) and interaction between Clavien-Dindo grade 2/3a and mean daily steps (p = 0.00038) are significant predictors of length of stay. The following variables were not significantly associated with length of stay: mean daily steps/sleep duration/sleep efficiency, average rate of change in these three variables, and changes in step count between successive postoperative days 1-5, sleep duration between successive postoperative days 2-5, and sleep efficiency between successive postoperative days 2-4. CONCLUSION: We demonstrated the utility of activity and sleep data from wearable biosensors in predicting length of stay. Patients with more severe complications may benefit more (i.e., reduced postoperative length of stay) from increased ambulation. However, overall, sleep duration/efficiency did not predict length of stay.
Asunto(s)
Técnicas Biosensibles , Procedimientos Quirúrgicos del Sistema Digestivo , Enfermedades Inflamatorias del Intestino , Dispositivos Electrónicos Vestibles , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/cirugía , Tiempo de Internación , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Depression and anxiety are comorbidities of inflammatory bowel disease (IBD), and it is now recommended to screen IBD patients for these conditions. We screened patients using a novel computerized adaptive testing technology and compared the screening results to measures of disease activity. METHODS: Consecutive patients at our tertiary IBD clinic were asked to complete the validated CAT-MH™ survey (Adaptive Testing Technologies, Chicago, IL); we then reviewed disease and patient characteristics. Clinical remission status was determined based on clinical, laboratory, endoscopy and imaging results. Statistical methods included Fisher's exact test and Pearson Chi-square tests to assess association. Univariable and multivariable analyses were performed. RESULTS: We included 134 patients, of which 34 (25.3%) screened positive for depression and 18 (13.4%) screened positive for anxiety. We identified 19 (55.9 %) and 10 (55.5%) patients who were previously undiagnosed for depression and anxiety, respectively. Patients in clinical remission were less likely to screen positive for depression (OR 0.19; 95%CI 0.07-0.50) and for anxiety (OR 0.30; 95%CI 0.10-0.91). Compared to patients with negative CRP values, patients with positive CRP were more likely to also screen positive for depression (p=0.025) and anxiety (p=0.15). CONCLUSIONS: We demonstrate the utility of a novel testing technology for screening patients with IBD for depression and anxiety. We found a large number of patients with previously undiagnosed anxiety or depression and a significant positive association between clinically active IBD and these mental health conditions. This work supports and informs recommendations for mental health screening in the IBD population.
RESUMEN
Patients with ulcerative colitis (UC) can experience periods of recurrent disease activity with a range of symptoms, including abdominal pain, rectal bleeding, urgency, and diarrhea. Although long-term remission will be achieved and maintained in most cases, the course of UC varies from patient to patient. Patients can be defined according to whether they are in remission or have mild, moderate, severe, or fulminant disease, and hospitalization can occur under different circumstances. In these cases, determining the next course of therapy is essential. The aim of this article is to present an approach to the treatment of high-risk UC in both the outpatient and inpatient settings. Also presented is a critical appraisal of alternative and emerging approaches to the management of patients with high-risk UC. Fundamental principles are key in the management of high-risk UC, including discussing the goals of treatment with the patient and family, assessing each patient's risk level and prognostic factors in addition to disease activity to inform therapeutic choices, understanding drug mechanisms and pharmacokinetics, and using objective measures to monitor disease response. In the treatment of all patients with high-risk UC, a balanced approach to deciding between medical and surgical options must be maintained.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Enfermedades Inflamatorias del Intestino , Vacunación , Antiinflamatorios/inmunología , Antiinflamatorios/farmacología , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/clasificación , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/uso terapéutico , Consenso , Gastroenterología/métodos , Gastroenterología/normas , Humanos , Inmunogenicidad Vacunal/efectos de los fármacos , Inmunogenicidad Vacunal/inmunología , Inmunomodulación/efectos de los fármacos , Inmunomodulación/inmunología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , Cooperación Internacional , SARS-CoV-2 , Vacunación/métodos , Vacunación/normasRESUMEN
BACKGROUND: This study aimed to analyze the association of coexisting sinusitis and IBD, establish significant factors involved in their development, and enable further biological correlation between these two diseases. METHODS: The IBD and Sinusitis Study at UChicago Medicine (TISSUe) is a retrospective, single-center study. We reviewed patients to confirm IBD and chronic sinusitis diagnoses. Case-control propensity score matching was performed using matched controls with IBD only or sinusitis only. Statistical methods included Chi-squared test and Wilcoxon rank sum test. Logistic regression analysis was performed, and factors were considered significant if p<0.05. RESULTS: Stratifying 214 patients with coexisting IBD and sinusitis, 176 patients had IBD first and 38 patients had sinusitis first. Multivariable analysis of factors associated with subsequent disease with matched controls determined that duration of disease, UC, steroid exposure ever, and younger age of IBD diagnosis were associated with subsequent sinusitis in patients with IBD; steroid exposure ever and duration of sinusitis were significantly associated with subsequent IBD in patients with sinusitis. CONCLUSIONS: This study suggests that IBD maintenance therapies are not associated with increased risk of sinusitis, as proposed by adverse events in clinical trial data; rather, UC diagnosis and duration of disease may be more influential in sinusitis development. While further studies are necessary, this study also demonstrates that sinusitis precedes IBD in some patients, probing its biological association with IBD and possible classification as an extraintestinal manifestation.
RESUMEN
BACKGROUND & AIMS: A subset of patients with Crohn's disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses. METHODS: We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%). RESULTS: Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 µg/g to 157 µg/g (P = .57). Among patients who had an HBI >4, a level of CRP ≥5mg/dL, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score ≤4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission. CONCLUSIONS: Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe.
Asunto(s)
Enfermedad de Crohn , Ustekinumab , Proteína C-Reactiva/metabolismo , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Complejo de Antígeno L1 de Leucocito , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Chronic inflammation in ulcerative colitis (UC) is associated with the development of colorectal neoplasia (CRN). A group at St. Mark's Hospital reported a novel cumulative inflammatory index that predicted the development of CRN in UC patients that we validated with an independent, well-described, matched, case-controlled cohort from the University of Chicago. METHODS: Cumulative inflammatory burden (CIB) was calculated by summing each histological inflammatory activity (HIA) score and multiplying it by the length of the surveillance interval. Persistency was defined by the number of surveillance episodes (with a severity score >2) divided by the total number of surveillance procedures. T tests compared the mean and maximum HIA scores, assessing mean and maximum severity, CIB, and persistency. RESULTS: Sixty-two UC patients (26 patients with CRN, 36 control patients without CRN) were analyzed. Fifty-five percent were men, mean disease duration was 20.6 years, and mean age at CRN diagnosis was 43.9. Of the CRN patients, 6 (23%) had colorectal cancer, 16 (62%) had low-grade dysplasia, and 4 (15%) had indefinite dysplasia. Using mean HIA scores, we found CIB to be statistically greater in CRN patients (P = 0.04). Using maximum HIA scores, we found CIB (P = 0.02), mean severity (P = 0.03), and persistency (P = 0.01) to be significantly greater in CRN patients. Maximum severity was numerically greater for mean and maximum HIA scores but did not reach significance. CONCLUSION: Cumulative histologic inflammation is significantly associated with the development of CRN in UC patients. This suggests a management strategy of controlling inflammation to reduce the risk of CRN and may influence the selection of surveillance intervals.
Asunto(s)
Colitis Ulcerosa , Neoplasias Colorrectales , Estudios de Casos y Controles , Estudios de Cohortes , Colitis Ulcerosa/complicaciones , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Femenino , Humanos , Inflamación/complicaciones , MasculinoRESUMEN
BACKGROUND AND AIMS: Socioeconomic status, race, and insurance can impact healthcare delivery and utilization in several chronic disease states. The primary aim of our study was to determine whether race and insurance status are predictors of having an appropriate workup for celiac disease and inflammatory bowel disease (IBD) when presenting with iron deficiency anemia (IDA) and chronic diarrhea. METHODS: Medical records of patients seen at the University of Chicago Medical Center between January 1, 2006, and September 20, 2017, were reviewed. Patients with two separate encounters within 6 months associated with the diagnosis codes for both IDA and chronic diarrhea were identified. Patients without a diagnosis code for IBD and celiac disease were further grouped as those that had an "appropriate" workup and those that did not. Factors associated with the appropriate evaluation were analyzed by univariate and multivariate logistic regression. RESULTS: In total, 899,701 records were searched. A total of 83 patients fit inclusion into the study (8 IBD, 3 CD, 72 neither IBD or CD). Black race was associated with a 91% decreased odds of having the appropriate workup on univariate (OR 0.090, 95%CI 0.017-0.475, p = 0.005) and age-adjusted multivariate analysis (OR 0.095, 95% CI 0.017-0.527, p = 0.007). Public insurance status was significantly associated with a 90% decreased odds of appropriate workup on univariate (OR 0.102, 95% CI 0.024-0.438, p = 0.002) and age-adjusted multivariate analysis (OR 0.104, 95% CI 0.021-0.513, p = 0.005). CONCLUSIONS: Black race and public insurance were significantly associated with not having an appropriate workup for IBD and celiac disease when presenting with iron deficiency and chronic diarrhea.
Asunto(s)
Anemia Ferropénica/etiología , Población Negra , Enfermedad Celíaca/complicaciones , Diarrea/etiología , Seguro de Salud , Síndrome del Colon Irritable/complicaciones , Anemia Ferropénica/diagnóstico , Enfermedad Celíaca/diagnóstico , Diarrea/diagnóstico , Humanos , Síndrome del Colon Irritable/diagnóstico , Oportunidad Relativa , Estudios RetrospectivosRESUMEN
Patients with inflammatory bowel disease (IBD) occasionally need a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) because of medically refractory colitis or dysplasia/cancer. However, pouchitis may develop in up to 70% of patients after this procedure and significantly impair quality of life, more so if the inflammation becomes a chronic condition. About 10% of patients with IBD who develop pouchitis require pouch excision, and several risk factors of the failure have been reported. A phenotype that has features similar to Crohn's disease may develop in a subset of ulcerative colitis patients following proctocolectomy with IPAA and is the most frequent reason for pouch failure. In this review, we discuss the diagnosis and prognosis of pouchitis, risk factors for pouchitis development, and treatment options for pouchitis, including the newer biological agents.