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Background and Aim: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient‐reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. Methods: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1–M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. Results: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. Conclusions: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups. [ABSTRACT FROM AUTHOR]

Background: To describe the frequency and impact of oral lesions and professional dental care costs in patients with inflammatory bowel disease (IBD) (i.e., Crohn disease [CD] or ulcerative colitis [UC]) compared to matched controls). Methods: IBD patients and matched controls were surveyed on general anamnestic information, eating and drinking habits, and oral health‐ and dental care‐related questions; IBD patients were additionally surveyed on oral lesions. Problems related to oral lesions and the amount of money spent for professional dental care in the past 12 months were defined as primary outcome parameters. Results: Answers from 1108 IBD patients and 3429 controls were analyzed. About 30% of the patients indicated having had problems with oral lesions, with CD patients having 46% higher odds and having them more often in a generalized form compared to UC patients. Further, self‐reported severe periodontitis increased the odds of having oral lesions by almost 2.3‐times. However, only about 12.5% of IBD patients were informed by their physician about oral lesions and about 10% indicated receiving treatment for them. Compared to controls, IBD patients required more often dental treatment and spent more money; specifically, UC and CD patients had 27 and 89% higher odds, respectively, for having spent ≥3000 DKK (ca. 440 USD) at the dentist compared to controls. Conclusions: IBD patients have more often oral health problems and higher expenses for professional dental care compared to matched controls. This included problems with IBD‐related oral lesions, but these are rarely addressed by the medical or dental team. [ABSTRACT FROM AUTHOR]

Background and Aim: The rate of ulcerative colitis (UC)‐related colorectal cancer (colitis‐associated carcinoma) is increasing. Estrogen receptor (ER) beta expression has been studied separately in patients with sporadic colorectal cancer and those with colitis‐associated carcinoma. However, no study has compared the expression in both of these cancer types. The present study aimed to evaluate the relationship between colitis‐associated carcinoma and ERs and assess whether the expression of ER beta influences cell proliferation. Methods: This study included 45 surgically operated colitis‐associated carcinomas, 43 high‐grade dysplasias, 34 low‐grade dysplasias, 36 sporadic colorectal cancers, 44 high‐grade adenomas, and 34 low‐grade adenomas. ER beta expression was evaluated with immunohistochemistry. Results: Colitis‐associated carcinoma showed significantly lower ER beta immunoexpression than sporadic colorectal lesions and high‐ and low‐grade dysplasia. In seven colitis‐associated carcinoma harboring both intensity score 3 (strong immunoexpression) and score 1 (weak immunoexpression) areas, the correlation among ER beta intensity, Ki‐67, and p21 labeling index was assessed; an area with an ER beta intensity score of 3 showed a higher Ki‐67 labeling index than that with score 1. In four out of the seven lesions, p21 labeling index was higher in the area of ER beta score 1 than in that of ER beta score 3. Conclusions: The data suggest that ER beta expression is an accelerating factor in colorectal tumors. This association may be lower in colitis‐associated carcinoma than in sporadic colorectal cancer. [ABSTRACT FROM AUTHOR]

We highlight the key aspects for the diagnosis of Postoperative pyoderma gangrenosum: "Pathergy phenomenon" at surgical site incisions; "Skip lesions": central venous catheter site lesions were similar to abdominal wall lesions despite distance between them; Lack of response to antibiotics or debridement; Immediate response to corticosteroid therapy. [ABSTRACT FROM AUTHOR]

Introduction: Many mucocutaneous conditions affect the skin and oral cavity. Common conditions include lichen planus, pemphigus, and pemphigoid. This case report shows an atypical presentation of a mucocutaneous condition wherein histopathology was required for definitive diagnosis and treatment. Case Presentation: A 51‐year‐old African American male self‐reported to a private periodontal practice with a chief complaint of sporadic painful oral lesions of about 2 months duration. The patient also reported painful throat lesions. He had been previously treated for a sore throat followed by unspecified inflammation of the epiglottis. Clinical examination revealed diffuse bilateral eye redness, numerous intraoral ulcerations on soft and hard palate and floor of the mouth with trouble swallowing. Oral and ocular presentation suggested a differential diagnosis of cicatricial pemphigoid. Pemphigoid and lichen planus were also considered. Ophthalmologic exam revealed only allergies and no other abnormality. Soft tissue biopsies showed intraepithelial separation between the spinous layer and basement membrane. Direct and indirect immunofluorescence showed strong immunoglobulin G and moderate C3 reactivity confirming a diagnosis of pemphigus vulgaris (PV). A rheumatologist initially treated the patient with a daily combination regimen of methylprednisolone and mycophenolate mofetil. Lesions improved after a few weeks on the regimen. Reduction of medications resulted in return of oral and throat lesions. Resumption of the regimen resulted in lesion remission. Azathioprine replaced the mycophenolate mofetil, and then was gradually stopped after methylprednisolone cessation. Lesions have not reappeared for 1 year. Conclusion: This case illustrates that early diagnosis of mucocutaneous lesions leads to proper treatment and possible remission. [ABSTRACT FROM AUTHOR]

Background Acute severe colitis ( ASC) is a serious condition with possible outcomes of emergency colectomy and mortality. Validated guidelines exist to help avoid these. Aims To examine local adherence to guidelines and identify (a) opportunities to improve care and (b) possible barriers to adherence. Methods Retrospective, hospital-wide audit of all patients with ASC during a 2-year period (2009-2010) at a major metropolitan hospital. Cases were identified by an electronic search of all discharges with International Classification of Diseases-10 codes for colitis, colectomy, ulcerative colitis or Crohn disease. Results Twenty-six patients had 30 ASC admissions (14 female). Most admissions were under gastroenterology (25), 4 (13%) were under general medicine and 1 was under general surgery. Only 8 patients' (26%) management (all under gastroenterology) included all major details: blood investigations, Clostridium difficile test, abdominal X-ray, colonic examination and venous thromboembolism prophylaxis. Only one patient had formal severity scoring on admission, and seven patients (24%) had descriptive severity recorded. On day 3, nine patients (30%) had some recorded severity assessment; however, no formal criteria were used. Four had colectomy, three during first admission and one on re-admission. Of these patients, three received cyclosporine prior to colectomy. The mean duration of admission was 10 days (standard deviation 10.54, range 1-61). Conclusion Opportunities to optimise care exist including formal severity assessments on days 1 and 3, better deep vein thrombosis/pulmonary embolism prophylaxis and prompt colonic examination. Admission under teams other than gastroenterology appeared to be a barrier to better care. Despite the low rate of ideal management, the colectomy rate was acceptably low at 20%. [ABSTRACT FROM AUTHOR]

This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of ‘indeterminate colitis’ (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain ‘hardcore’ histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review. [ABSTRACT FROM AUTHOR]

Leptin, a recently discovered protein, acts as a hormonal feedback signal in regulating adipose tissue mass via hypothalamic mechanisms. Inflammatory bowel disease is often associated with anorexia and weight loss. The aim of the present study was to investigate serum leptin levels during the time course of the acute phase of ulcerative colitis (UC) and to evaluate whether leptin leads to anorexia and bodyweight loss in these patients. Serum leptin levels of 29 male patients with acute UC and 17 healthy controls with similar age, sex and body mass index (BMI) were measured. Erythrocyte sedimentation rate (ESR), BMI, serum albumin and C-reactive protein concentrations, and white blood cell counts were determined. A significant increase in serum leptin levels was found in patients with acute UC when compared with controls (5.89 ± 2.06 ng/mL and 3.64 ± 1.69 ng/mL, respectively; p = 0.001). There was no correlation between leptin levels and BMI. Our findings in the acute stage of UC suggest that increased serum leptin levels may contribute to anorexia and weight loss. However, an inappropriate increase in leptin levels is independent of body mass in acute UC, and we believe that other factors may be involved in inflammation-induced increases in leptin levels. [ABSTRACT FROM AUTHOR]

Aim: Diagnostic delay for inflammatory bowel disease (IBD) is frequent, especially in paediatric patients. Scintigraphy with labelled leucocytes has been proposed as a very sensitive diagnostic tool for detecting bowel inflammation. The aim of this study was to evaluate the sensitivity and specificity of immunoscintigraphy in the diagnosis and follow-up of children with IBD and to compare this technique with other diagnostic techniques.Methods: Sixty-six children with histologically confirmed IBD were enrolled in the study. Twenty-one children in whom IBD was suspected but subsequently not confirmed were used as controls. A total of 138 immunoscintigraphies were performed using 99mTechnetium-labelled monoclonal anti-granulocyte antibodies. Immunoscintigraphy was also compared with other diagnostic techniques.Results: Overall sensitivity of monoclonal antibody immunoscintigraphy (MoAb-IS) in patients with clinically active disease was 94% for Crohn's disease (CD) and 85% for ulcerative colitis (UC). Ultrasonography, endoscopy and radiology were carried out at the same time in 29 patients with CD and in 6 patients with UC: sensitivity of IS was 90% compared with 76% of colonoscopy, 75% for enemas, and 55% for sonography. IS was negative (specificity) in 24% of patients with CD and in 67% of patients with UC during remission, and in 64% of controls with other causes of intestinal inflammation. Diagnostic delay was significantly shorter when compared with a historical cohort of patients.Conclusion: Immunoscintigraphy is a highly sensitive detector of intestinal inflammation in young patients with IBD and can be useful for reducing diagnostic delay. However, its specificity is low and all positive cases must be confirmed histologically. [ABSTRACT FROM AUTHOR]

Unlabelled: Even a minor decrease in birthweight predisposes to adult disease. Inflammatory bowel disease (IBD) in the mother is a risk factor for low birthweight and preterm infants. This study investigated the effect of IBD in the mother or father, adjusting for confounders, on the newborn infant, with the focus on birthweight and pregnancy duration. A total of 10399 single-birth mother-infant pairs was prospectively enrolled within the ABIS project (All Babies In Southeast Sweden). Outcome measures included birth week, preterm birth (<37 wk), birthweight, low birthweight (<2500 g), birth length, caesarean section and neonatal hospital care. Ulcerative colitis (UC) in the mother was associated with lower birthweight in the infant (adjusted difference: -330 g, adjusted 95% confidence interval: -509 to -150 g, p < 0.001), and with even lower birthweight when the mother was treated with Mesalazine or steroids. No decrease in birthweight was seen in infants whose mother suffered from Crohn's disease (CD) (adjusted difference: -65 g, adjusted 95% confidence interval: -354 to 224 g, p > 0.05). Maternal UC or CD did not affect the pregnancy duration. The neonatal outcome of infants whose father suffered from UC and CD did not differ from the control group.Conclusion: UC in the mother affects the birthweight of the infant, which may predispose to future disease in the infant. Most women and men with UC and CD can, however, expect a healthy child with neither preterm birth nor low birthweight. [ABSTRACT FROM AUTHOR]

AbstractBackground: The prevalence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) does not significantly vary in ethnically diverse populations. The prevalence of p-ANCA is high in ulcerative colitis and primary sclerosing cholangitis. While the prevalence of ulcerative colitis in Asian populations is low, it is interesting to know the prevalence of p-ANCA in such a population. Methods: Sera from 33 cases of ulcerative colitis diagnosed during the last 10 years at the diarrhea clinic, Division of Gastroenterology, Siriraj Hospital, were prospectively compared with case controls consisting of 15 cases of diarrhea from non-inflammatory bowel diseases and 25 non-diarrheic patients. Indirect immunofluorescence assay was used to detect p-ANCA in all the sera. Results: Positive p-ANCA tests were found in 13 of the 33 patients with ulcerative colitis and in one of the 40 controls. Sensitivity of the test was 39.4% and the specificity was 97.5%. The one patient with positive p-ANCA in the control group was the patient with irritable bowel syndrome. Of the 13 p-ANCA-positive ulcerative colitis patients, two cases were found to have proctosigmoiditis, seven cases had left-sided colitis, and four cases had pancolitis. Perinuclear antineutrophil cytoplasmic antibodies was one of the 22 cases of first-degree relatives of ulcerative colitis patients (22 relatives from 12 index ulcerative colitis cases). There was no correlation between the positivity of p-ANCA and disease activity, and extent of the disease. Conclusion: The prevalence of p-ANCA in Thai patients with ulcerative colitis (39.4%) is lower than that in the Western population. Although the prevalence of p-ANCA is low in the Thai population, it should serve as a useful tool in diagnosing ulcerative colitis in this part of the world where the disease is uncommon and difficult to diagnose. The negativity of p-ANCA in almost all first-degree relatives of Thai ulcerative colitis patients should be further... [ABSTRACT FROM AUTHOR]

In the 1970s several reports highlighted the long delay in diagnosis often experienced by children with Crohn's disease. In recent years this disorder has attracted much publicity, and many believe that the incidence has increased substantially. The aim of this investigation was to determine whether heightened awareness had shortened the interval to diagnosis, improved clinical management and reduced morbidity. A retrospective study was therefore carried out on 112 children with inflammatory bowel disease (64 Crohn's disease, 41 ulcerative colitis, 7 indeterminate colitis) referred to a paediatric gastroenterology department in the UK between 1994 and 1998. In Crohn's disease the median interval to diagnosis was 47 wk (maximum 7 y). In those without diarrhoea this was longer (66 vs 28 wk; p = 0.005). In ulcerative colitis the median interval was 20 wk (maximum 3 y). Even in severe colitis the median interval was 5.5 wk (range 3-9 wk) and 4 required urgent colectomy soon after referral. Many with unrecognized Crohn's disease had undergone inappropriate treatments, such as growth hormone or psychiatric therapy. Nineteen (17%) had undergone endoscopic investigations in adult units prior to referral. Malnutrition was equally common in Crohn's disease and ulcerative colitis (11%). Short stature was present in 19% with Crohn's disease, and 5% with ulcerative colitis, and was severe in 8% with Crohn's disease. There was a significant correlation between symptom duration and the degree of growth impairment present (r [sub s] =-0.4; p = 0.004) Conclusion: This study suggests that late diagnosis and inappropriate investigation and management are still significant problems. [ABSTRACT FROM AUTHOR]

Aims : To assess whether Ki67 and p53 immunostaining may assist the diagnosis and grading of ulcerative colitis-related dysplasia. Methods and results : Location of Ki67 staining and location and intensity of p53 staining were assessed in ulcerative colitis (UC) cases showing the features of high-grade dysplasia (HGD, n = 14), low-grade dysplasia (LGD, n = 22), ‘indefinite for dysplasia’ (n = 12), or regenerative atypia (RA, n = 22). Good intra- and inter-observer reproducibilities were demonstrated in the performance of these assessments. All the dysplasia cases showed extension of Ki67 staining above the basal third of the crypt. Moderate intensity p53 staining was seen in 10/22 RA cases, but strong intensity p53 staining was seen only in cases of dysplasia. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt. Conclusions : Restriction of Ki67 staining to the basal third of the crypt appears to exclude a diagnosis of dysplasia whereas strong intensity p53 staining suggests a diagnosis of dysplasia. Restriction of Ki67 or p53 staining to the basal two-thirds of the crypt appears to exclude a diagnosis of HGD. [ABSTRACT FROM AUTHOR]

The role of psychosocial factors in the understanding of inflammatory bowel disease (IBD) has been a major area of clinical interest and psychosomatic research. This paper explores the scientific basis for the following contentions: (1) psychosocial factors such as stressful life events are associated with symptom onset and exacerbation; (2) research in brain­gut peptides and the new fields of psychoimmunology and psychoneuroendocrinology may establish the physiological basis for this clinical observation; (3) while there is no proof for the psychosomatic specificity hypothesis, certain psychodynamic observations, particularly conflicts relating to real or threatened loss and extreme dependency with parental figures, are frequently observed; (4) there is a higher prevalence of psychiatric disorders (particularly depression) among patients with Crohn's disease; (5) the psychosocial impact of these disorders may be considerable, yet patient adjustment and perceived quality of life is generally favourable. [ABSTRACT FROM AUTHOR]

The possibility of autoimmune type I reactions to cellular constituents was investigated in 22 patients with ulcerative colitis, 12 with Crohn's disease, and in 22 healthy volunteers. Nuclear components and colon mucosa fragments were tested as potential antigens by the basophil histamine release technique One of 12 patients with ulcerative colitis responded to sonicated leukocyte nuclei and one of 12 patients with Crohn's disease responded to both nuclei and RNA. Increased serum levels of total IgE and antinuclear antibodies of IgE class were found in one and three of the 24 patients, respectively Histamine release caused by colon mucosa fragments was not observed in a separate study consisting of 10 ulcerative colitis patients and 10 healthy volunteers. Autoimmune type I allergy to cellular constituents does not seem to be of significance for chronic inflammatory bowel disease and thus could not explain the involvement of tissue mast cells and eosinophils in this condition. [ABSTRACT FROM AUTHOR]

Liver tissue specimens taken at colectomy from 29 patients with chronic ulcerative colitis were studied by electron microscope. The fine-structural alterations were correlated with light microscopy and with biochemical liver function tests. The purpose was to identify ultrastructural features which could explain the pathogenesis of sclerosing cholangitis. Severely injured bile-duct epithelial cells were seen in three out of the eight light-microscopically diagnosed cholangitis cases, in the two cases of non-specific reactive hepatitis, and in the two fatty livers. Four cholangitis cases had, in heavily thickened bile-duct basement membranes, translucent areas containing bile-like material. Bile-duct microvilli were often blunted, and reduced in number. Intracanalicular bile thrombi and bile inclusions in hepatocytes were seldom seen, mostly but not exclusively in cholangitis. The fine-structural alterations apparently represent various stages of liver injury. These findings do not appear to be specific, but their prominence seems to correlate with the progression of the disease, at least in the case of histological parameters, but also in serum enzyme activities indicative of cholestasis. The bile-like electron-dense material found in proliferating basement membranes, very possibly regurgitated into the injured bile-duct wall after epithelial injury, could enhance the development of periductal fibrosis, leading to progression of sclerosing cholangitis. [ABSTRACT FROM AUTHOR]