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BACKGROUND & AIMS: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class. CONCLUSIONS: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.
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BACKGROUND: As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS: To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS: We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS: Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION: Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.
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BACKGROUND: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS: We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS: The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS: Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).
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Enfermedad de Crohn/tratamiento farmacológico , Ustekinumab/uso terapéutico , Adulto , Femenino , Humanos , Quimioterapia de Inducción , Infusiones Intravenosas , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Inducción de Remisión , Ustekinumab/efectos adversos , Ustekinumab/inmunología , Ustekinumab/farmacocinéticaRESUMEN
BACKGROUND & AIMS: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. METHODS: We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor ß common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared. RESULTS: In the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P = 8.52 × 10(-4)); the finding was validated in the replication cohort (combined P = 3.42 × 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance. CONCLUSIONS: In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.
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Enfermedad de Crohn/genética , Subunidad beta Común de los Receptores de Citocinas/genética , Mutación del Sistema de Lectura , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Judíos/genética , Estudios de Casos y Controles , Enfermedad de Crohn/etnología , Enfermedad de Crohn/patología , Femenino , Humanos , Intestinos/citología , Intestinos/patología , Masculino , Monocitos/metabolismo , Factores de Riesgo , Transducción de Señal/genéticaRESUMEN
BACKGROUND & AIMS: Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. METHODS: We performed a retrospective analysis of data from 333 patients with IBD treated at 8 academic medical centers who developed cancer and subsequently received treatment with anti-tumor necrosis factor (TNF), anti-TNF with an antimetabolite (thiopurines, methotrexate), antimetabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated by using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared by using the log-rank test. RESULTS: During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible because of the relatively small sample sizes. There was no difference in time to incident cancer (P = .14) or type of incident cancer (P = .61) among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF, 0.32; 95% confidence interval [CI], 0.09-1.09; HR for anti-TNF with an antimetabolite, 0.64; 95% CI, 0.26-1.59; HR for an antimetabolite, 1.08; 95% CI, 0.54-2.15) or time to subsequent cancer between study arms (P = .22). CONCLUSION: On the basis of a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an antimetabolite after cancer was not associated with an increased risk of incident cancer, compared with patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.
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Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Neoplasias/epidemiología , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenAsunto(s)
Fragilidad , Enfermedades Inflamatorias del Intestino , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Readmisión del Paciente , Factores de RiesgoRESUMEN
Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10â»6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined pâ=â2×10â»8; combined odds ratio ORâ=â1.48), 2p15 (rs6545946, pâ=â7×10â»9; ORâ=â1.16), 8q21.11 (rs12677663, pâ=â2×10â»8; ORâ=â1.15), 10q26.3 (rs10734105, pâ=â3×10â»8; ORâ=â1.27), and 11q12.1 (rs11229030, pâ=â8×10â»9; ORâ=â1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.
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Enfermedad de Crohn/genética , Estudio de Asociación del Genoma Completo , Judíos/genética , Cromosomas Humanos Par 5/genética , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Humanos , Desequilibrio de Ligamiento , Población BlancaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Seventy-nine US and Canadian centers. SUBJECTS: Patients aged ≥ 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week. METHODS: Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8. RESULTS: Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred. CONCLUSION: Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).
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Alprostadil/análogos & derivados , Analgésicos Opioides/efectos adversos , Agonistas de los Canales de Cloruro/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Alprostadil/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Lubiprostona , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Activated granulocytes and monocytes may contribute to the pathogenesis of Crohn's disease (CD). In small, uncontrolled studies, granulocyte/monocyte apheresis (GMA) has shown promise in treating CD. We conducted a randomised, double-blind study to compare GMA with a sham procedure in patients with moderate to severe CD. DESIGN: Patients with active CD as defined by a Crohn's Disease Activity Index (CDAI) of 220-450 were randomly allocated in a 2:1 ratio to treatment with GMA using the Adacolumn Apheresis System (JIMRO, Takasaki, Japan) or sham apheresis. Ten apheresis sessions were scheduled over a 9-week period, and efficacy was evaluated at week 12. The primary end point was the proportion of patients achieving clinical remission (CDAI score ≤ 150 without use of prohibited drugs). RESULTS: Clinical remission was achieved by 17.8% of patients in the GMA group (n = 157) compared with 19.2% of those in the sham control group (n = 78) (absolute difference--1.4% (95% CI--12.8% to 8.5%), p = 0.858). Clinical response (defined as a ≥ 100-point decrease in CDAI) was achieved by 28.0% and 26.9% of patients in the GMA and sham groups, respectively (p = 1.000). The two treatments produced similar changes from baseline in CDAI and quality of life, as well as in disease severity assessed endoscopically. The incidence and types of adverse events did not differ between groups. CONCLUSIONS: GMA was well tolerated, but this study did not demonstrate its effectiveness over a sham procedure in inducing clinical remission or response in patients with moderate to severe CD.
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Eliminación de Componentes Sanguíneos , Enfermedad de Crohn/terapia , Granulocitos/inmunología , Monocitos/inmunología , Adulto , Eliminación de Componentes Sanguíneos/efectos adversos , Eliminación de Componentes Sanguíneos/métodos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/fisiopatología , Enfermedad de Crohn/psicología , Método Doble Ciego , Endoscopía Gastrointestinal/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Calidad de Vida , Inducción de Remisión/métodos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Spirochete colonization of the gastrointestinal tract is a poorly understood phenomenon presenting with varying signs and symptoms. Due to the lack of a unified approach and its varying presentations, the management decision for intestinal spirochetosis (IS) has always been challenging. While metronidazole is the commonly preferred antimicrobial treatment, it remains unclear if therapeutic intervention is indicated for everyone, especially asymptomatic patients. We present three patients, diagnosed with IS. They presented with varying demographics, clinical presentations, and past medical histories and underwent different clinical managements. Our decisions for treatment not only included presenting symptoms but also factors like history of pre-existing gastrointestinal diseases, age, and immune status.
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Juvenile polyposis syndrome lies within the family of hamartomatous polyposis syndromes characterized by polyps that appear benign but harbor an increased risk of colorectal and gastric cancer. This 27-year-old man with severe ulcerative colitis was discovered to have concomitant juvenile polyposis syndrome during diagnostic workup for gastrointestinal bleeding. The implications of this rare association complicate both diagnostic and treatment modalities since both diseases confer an increased risk of cancer.
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The management of inflammatory bowel disease in the older patient extends beyond the gastrointestinal tract. Pre-existing comorbidities, polypharmacy, functional status and physical reserve can impact disease course, response to therapy and quality of life. Current therapeutic endpoints may not be as immediately applicable to the older IBD patient at higher risk for adverse outcomes. This review focuses on the latest studies addressing the natural history, clinical course and therapeutic outcomes among the older IBD cohort.
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Corticoesteroides/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Neoplasias Colorrectales/epidemiología , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Neoplasias Cutáneas/epidemiología , Corticoesteroides/uso terapéutico , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/uso terapéutico , Comorbilidad , Interacciones Farmacológicas , Humanos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/epidemiología , Polifarmacia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
As the prevalence of older adults with inflammatory bowel disease (IBD) is rising, understanding the unique challenges in both diagnosis and management is becoming increasingly important. Knowledge of phenotypic differences as well as overlapping symptoms with other medical conditions is critical to obtaining a timely diagnosis of IBD in older adults. Although older adults with IBD are at higher risk for adverse events compared with younger adults with IBD, recent data have suggested that ongoing disease activity may be a significant driver of adverse clinical outcomes rather than use of current treatment modalities. Ultimately, earlier and effective treatments can improve outcomes and quality of life for older adults with IBD. However, to help improve medical decision-making, clinicians must move away from the use of chronological age alone and begin to integrate measures of biological age, such as frailty and sarcopenia, into risk stratification tools. This article reviews the management considerations for older adults with IBD and provides the rationale for incorporating measures of biological age into current practice.
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Background: The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. Objectives: We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. Design: We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. Methods: Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. Results: From 1 March 2020 to 31 August 2021, there were 2508 patients with IBD who had at least one telehealth appointment, with 1088 (43%) having Crohn's disease (CD), 1037 (41%) having ulcerative colitis (UC), and 383 (15%) having indeterminate colitis. Of the initial telehealth visits, 519 (21%) were not completed, including 435 (20%) among patients <60 years as compared to 84 (23%) among patients ⩾60 years (p = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. Conclusion: Patients with CD, females, and those with less social support were at higher risk for missed telehealth appointments, as were adults >80 years. Engaging older adults via telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.
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The incidence and prevalence of inflammatory bowel disease (IBD) is increasing in the elderly population. Compared with patients with onset during younger years, patients with elderly-onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas aging-related biological changes, such as immunosenescence and dysbiosis, are associated with elderly-onset IBD. Frailty is an increasingly recognized predictor of adverse outcomes. As an increasingly wider array of biologic and small molecule therapeutic options becomes available, data regarding efficacy and safety of these agents in patients are paramount given the unique characteristics of this population.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Anciano , Biología , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/terapiaRESUMEN
The management and understanding of Crohn's disease (CD) continues to evolve quickly. Intestinal strictures were previously thought to be an inevitable result of irreversible fibrosis caused by chronic inflammation. However, increased understanding of the dynamic nature of strictures and of the pathophysiology of this condition has highlighted emerging targets for potential treatment. In the diagnosis of strictures, a distinction must be made between inflammatory and fibrotic types, as the former may respond to medical therapy. Emerging technologies, such as dual-energy computed tomography enterography and iodine density, have allowed more accurate characterization of strictures. Surgical and endoscopic treatment remains the mainstay for fibrotic strictures, but developments in systemic and intralesional biologic therapy have shown efficacy. This article reviews the pathophysiology of this debilitating complication of CD as well as current and emerging diagnostics and treatments.
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The growing recognition of the older inflammatory bowel disease (IBD) patient is heightened by the entry of the 77.2 million baby boomers who will turn 65 beginning of 2011. It is anticipated that this will occur at a rate of 10,000 per day or 4 million per year for the next 19 years. The management of IBD in this population is complex because of problems with co-morbidities, polypharmacy, impaired mobility, and cognition, as well as difficult social and financial issues. This review focuses on the older IBD patient's unique concerns and provides guidance in their diagnosis and management.
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Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/terapia , Corticoesteroides/uso terapéutico , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Diagnóstico Diferencial , Humanos , Factores Inmunológicos/uso terapéutico , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/metabolismo , Mesalamina/uso terapéutico , Persona de Mediana EdadRESUMEN
Screening for prostate cancer after restorative proctocolectomy with ileal pouch-anal anastomosis can be challenging. Diagnostic biopsy for an elevated level of prostate-specific antigen may present difficulties as well. No guidelines have been issued regarding the value and accuracy of digital examination and the best route to obtain prostate biopsy specimens. A screening and diagnostic algorithm for prostate cancer was developed by an expert consensus panel.
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Algoritmos , Biopsia/métodos , Reservorios Cólicos , Enfermedades Inflamatorias del Intestino/cirugía , Proctocolectomía Restauradora , Neoplasias de la Próstata/diagnóstico , Anastomosis Quirúrgica , Gastroenterología/métodos , Humanos , Masculino , Tamizaje Masivo , Guías de Práctica Clínica como Asunto , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patologíaRESUMEN
The incidence and prevalence of inflammatory bowel disease (IBD) is rising in the elderly population. Compared with patients with onset during their younger years, patients with elderly onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas biological changes associated with aging including immunosenescence, dysbiosis, and frailty have a greater impact on disease outcomes. With the advent of an increasingly wider array of biologic and small-molecule therapeutic options, data regarding efficacy and safety of these agents in elderly IBD patients specifically are paramount, given the unique characteristics of this population.
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BACKGROUND & AIMS: Interleukin-12 and interleukin-23 are inflammatory cytokines implicated in Crohn's disease pathophysiology. Ustekinumab is a monoclonal antibody against the p40 subunit of interleukin-12/23. METHODS: We performed a double-blind, cross-over trial of the clinical effects of ustekinumab in 104 patients with moderate-to-severe Crohn's disease (population 1). Patients were given subcutaneous placebo at weeks 0-3, then ustekinumab at weeks 8-11; subcutaneous ustekinumab at weeks 0-3, then placebo at weeks 8-11; intravenous placebo at week 0, then ustekinumab at week 8; or intravenous ustekinumab at week 0, then placebo at week 8. Furthermore, an open-label trial evaluated the effects of 4 weekly subcutaneous injections or 1 intravenous infusion of ustekinumab in 27 patients who were primary or secondary nonresponders to infliximab (population 2). RESULTS: In population 1, clinical response rates for the combined groups given ustekinumab and placebo were 53% and 30% (P = .02), respectively at weeks 4 and 6, and 49% and 40% (P = .34), respectively at week 8. In a subgroup of 49 patients who were previously given infliximab (neither primary nor secondary nonresponders), clinical response to ustekinumab was significantly greater than the group given placebo (P < .05) through week 8. In population 2, the clinical responses at week 8 to subcutaneous and intravenous ustekinumab were 43% and 54%, respectively. There was no increase in the number of adverse or serious adverse events in patients given ustekinumab through week 8 compared with placebo. CONCLUSIONS: Ustekinumab induced a clinical response in patients with moderate-to-severe Crohn's disease, especially in patients previously given infliximab.