Diagnosing Pouchitis

PURPOSE: Pouchitis represents a serious threat to patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The frequency of pouchitis is high, and it implies the risk of pouch failure and the risk of malignant mucosal transformation in the pouch. Early detection and precise classification of the inflammatory process are required for adequate therapy, which might be facilitated using a scoring system. The aim of the present study was to validate two existing scoring systems in routine outpatient practice. METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis Disease Activity Index developed at the Mayo Clinic were simultaneously prospectively applied in a consecutive series of 103 outpatient consultations of 41 patients at our hospital and comparatively validated against the diagnosis of pouchitis or no pouchitis concurrently made by a physician and a surgeon. RESULTS: The median score of examinations in which the clinicians diagnosis was consistent with pouchitis were significantly higher than those of examinations inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis Activity Score, 17 (interquartile range, 14–21) and 8 (interquartile range, 5–10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile range, 5–8) and 2.5 (interquartile range, 1–4), respectively, P < 0.001). The sensitivity and specificity in the two total scores were 84 and 79.5 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent, respectively (Pouchitis Disease Activity Index); in the field clinical manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index); in the field endoscopic manifestations 88 and 83.3 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively (Pouchitis Disease Activity Index); and in the field histologic manifestations 72 and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and 96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index by 2 points (pouchitis: score 5) would result in an 88 percent sensitivity and a 67 percent specificity. CONCLUSIONS: Specificity and sensitivity of the Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be lowered to reach an acceptable sensitivity and specificity. The very poor validity of the field clinical manifestations in diagnosing pouchitis emphasizes the need for endoscopic and histologic examination for detection of pouchitis. The issue of whether the diagnosis of pouchitis should be based on endoscopic and histologic features alone, instead of additionally taking clinical features into account, should be addressed in future studies.     

The ileo-anal pouch procedure: Complications, quality of life, and long-term results

The ileo-anal pouch procedure: Complications, quality of life, and long-term results. Restorative proctocolectomy with construction of an ileal pouch-anal anastomosis (IPAA) has evolved as the surgical therapy of choice for patients with ulcerative colitis (UC) and patients with familial adenomatous polyposis (FAP). 662 patients (493 UC, 169 FAP) consecutively received IPAA. Marked differences were observed between UC and FAP patients regarding the rates of overall complications (33.1 % vs. 12.5 %), pouchitis (29 % vs. 2 %), and pouch extirpation (3.2 % vs. 0.6 %). Pouchitis occurred as primary (79 %) and secundary (21 %) form, with acute (67.2 %) or chronic (32.8 %) course. Each form and course required specific therapy. Chronic pouchitis implies the risk of malignant transformation of the pouch mucosa. Quality of life improves significantly after IPAA in patients with UC and is equal to that in normal individuals, in UC and FAP, if postoperative complications are either prevented or under control.     

Antagonism of TIM-1 blocks the development of disease in a humanized mouse model of allergic asthma

Studies in mice and humans have revealed that the T cell, immunoglobulin, mucin (TIM) genes are associated with several atopic diseases. TIM-1 is a type I membrane protein that is expressed on T cells upon stimulation and has been shown to modulate their activation. In addition to a recently described interaction with dendritic cells, TIM-1 has also been identified as a phosphatidylserine recognition molecule, and several protein ligands have been proposed. Our understanding of its activity is complicated by the possibility that TIM-1 possesses multiple and diverse binding partners. In order to delineate the function of TIM-1, we generated monoclonal antibodies directed to a cleft formed within the IgV domain of TIM-1. We have shown here that antibodies that bind to this defined cleft antagonize TIM-1 binding to specific ligands and cells. Notably, these antibodies exhibited therapeutic activity in a humanized SCID model of experimental asthma, ameliorating inflammation, and airway hyperresponsiveness. Further experiments demonstrated that the effects of the TIM-1–specific antibodies were mediated via suppression of Th2 cell proliferation and cytokine production. These results demonstrate that modulation of the TIM-1 pathway can critically influence activated T cells in a humanized disease model, suggesting that TIM-1 antagonists may provide potent therapeutic benefit in asthma and other immune-mediated disorders.     

Male partner experiences of females with an acquired brain injury: An interpretative phenomenological analysis

Acquired brain injury (ABI) not only has an impact on the survivor, but also on the partner and personal relationships as a whole. The present study aimed to investigate the male partner experience of living with a female with an ABI; exploring role change, intimacy and future expectations. Semi-structured interviews were conducted with six male partners of five females with a subarachnoid haemorrhage and one female with a traumatic brain injury. Interviews were transcribed verbatim and analysed in depth using Interpretative Phenomenological Analysis (IPA). Four main themes captured the male partner's lived experience; “Entering the unknown world of ABI”, “Imprisoned by the ABI”, “Compassion without self-compassion”, and “Holding on to hope”. The accounts uncovered the male partner's journey following ABI; the unpredictability, sorrow, frustration, and finally acceptance and commitment to their partner. They identified the limited support available for partners following ABI; the sense of feeling forgotten by services and the need for information and support in the acute stages. Rehabilitation needs to take a systemic and longer-term focus, supporting both the survivor and their partner through the journey of ABI.     

Interfollicular Fibrosis in the Thyroid of the Harbour Porpoise: An Endocrine Disruption?

Previous studies have described high levels of polychlorobiphenyls (PCB), polybrominated diphenylether (PBDE), toxaphene, p,p′-dichlorodiphenyltrichloroethane (DDT), and p,p′-dichlorodiphenyldichloroethylene (DDE) in the blubber of the harbour porpoise from the North Sea raising the question of a potential endocrine disruption in this species. In the present study, the thyroids of 57 harbour porpoises from the German and Danish (North and Baltic Seas), Norwegian, and Icelandic coasts have been collected for histological and immunohistological investigations. The number of follicles and the relative distribution of follicles, connective, and solid tissues (%) were quantified in the thyroid of each individual. Then, the potential relationship between the thyroid morphometry data and previously described organic compounds (namely, PCB, PBDE, toxaphene, DDT, and DDE) was investigated using factor analysis and multiple regressions. Thyroid morphology differed strongly between sampling sites. Porpoises from the German (North and Baltic Seas) and Norwegian coasts displayed a high percentage of connective tissues between 30 and 38% revealing severe interfollicular fibrosis and a high number of large follicles (diameter >200 μm). A correlation-based principal component analysis (PCA) revealed two principal components explaining 85.9% of the total variance. The variables PCB, PBDE, DDT, and DDE compounds loaded highest on PC1 whereas toxaphene compound loaded most on PC2. Our results pointed out a relationship between PC1 (PCBs, PBDE, DDE, and DDT compounds) and interfollicular fibrosis in the harbour porpoise thyroids. Such an association is not alone sufficient for a cause–effect relationship but supports the hypothesis of a contaminant-induced thyroid fibrosis in harbour porpoises raising the question of the long-term viability in highly polluted areas.