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.     

Idiopathic cholangiopathy in a biliary cast syndrome necessitating liver transplantation following head trauma

The development of total biliary casts is very unusual, especially in patients who have not undergone liver transplantation. The aetiology of these casts is uncertain but several factors are believed to play a role, including periods of fasting, haemolysis, cholangitis and recent surgery. Resultant bile stasis and/or gallbladder hypocontractility promote sludge and subsequent stone formation. Here we present the case of a previously well 66-year-old woman who developed a total biliary cast several weeks after being involved in a road traffic accident during which she sustained head injuries but no obvious liver insult. This cast was removed at laparotomy but the patient had resultant diffuse biliary tree abnormalities and persistent cholestasis and subsequently required a liver transplant. The possible aetiologies of biliary cast formation and subsequently cholangiopathy necessitating transplantation in this patient are described.     

Drug repurposing and emerging adjunctive treatments for schizophrenia

Introduction: Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial. Nevertheless, the understanding of the pathophysiology of this syndrome, concise diagnostic methods and more effective and tolerable treatments are still lacking. Thus, innovative approaches and the exploration of new territories are required.

Areas covered: An overview of repurposed drugs and emerging treatments for schizophrenia is presented, focusing on randomized, controlled trials and meta-analyses.

Expert opinion: Despite many years of drug research, several needs in the treatment of schizophrenia including the safety and tolerability, stage-dependent and personalized approaches, as well as drug delivery and sustainability have not been addressed sufficiently. Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs (e.g., acetylsalicylic acid, celecoxib and minocycline), as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones (e.g., estrogen, raloxifene and oxytocin), glutamatergic (e.g., glycine and d-serine) and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoidmodulator, represent promising agents in this field.     

PD-L1 – inhibitors in neuroendocrine neoplasia: Results from a real-life study

Immune check-point inhibitors (ICIs) have changed our view on how to treat cancer. Despite their approval in treatment of many different cancers, efficacy of immune check-point inhibitors (ICI) in neuroendocrine neoplasia is limited and poorly understood. Established treatment options of neuroendocrine tumors (NET) and neuroendocrine carcinomas (NECs) are based on surgery, tumor-targeted medical treatments, Peptide Receptor Radionuclide Therapy (PRRT), and locoregional therapies. However, in many patients these treatments lose efficacy over time, and novel therapies are urgently needed. We report on 8 patients diagnosed with neuroendocrine neoplasms (NEN) that were treated with ICI (pembrolizumab, avelumab, nivolumab plus ipilimumab) as salvage therapy. In this cohort, we observed tumor response with partial remission in 3 patients and stable disease in 1 patient. Four patients showed progressive disease. Of note, responses were observed both in PD-L1 positive and PD-L1 negative patients. Here, we discuss clinical courses of these patients in the context of available literature to highlight limitations and drawbacks currently preventing the use of ICI in routine management of patients with NEN.     

Psychometric properties of the Recovery Assessment Scale in a sample with substance use disorder

Background: Conceptualisations of recovery from substance use disorder (SUD) and mental illness overlap significantly, and the rate of comorbidity of these problems is high. This study investigated the psychometric properties of the Recovery Assessment Scale (RAS), a measure originally developed for individuals with mental illness. Method: A sample of 1094 people with SUD attending residential treatment services provided by the Australian Salvation Army completed the RAS and other outcome measures at admission. Results: Confirmatory factor analysis (CFA) indicated a poor fit of the data to the five factor solution previously identified in mental illness samples. Exploratory factor analysis, however, produced three of the five factors included in the CFA, and two factors which arranged constructs in a slightly different manner from previous factor analytic studies in samples with mental illness. Correlations of these factors with other symptom distress and recovery measures indicated satisfactory convergent and divergent validity. Conclusions: The study provides modest support for the use of the RAS in groups with SUD.