Impact of thiopurines and anti-tumour necrosis factor therapy on hospitalisation and long-term surgical outcomes in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the large bowel and is associated with a significant risk of both requirement for surgery and the need for hospitalisation. Thiopurines, and more recently, anti-tumour necrosis factor (aTNF) therapy have been used successfully to induce clinical remission. However, there is less data available on whether these agents prevent long-term colectomy rates or the need for hospitalisation. The focus of this article is to review the recent and pertinent literature on the long-term impact of thiopurines and aTNF on long-term surgical and hospitalisation rates in UC. Data from population based longitudinal research indicates that thiopurine therapy probably has a protective role against colectomy, if used in appropriate patients for a sufficient duration. aTNF agents appear to have a short term protective effect against colectomy, but data is limited for longer periods. Whereas there is insufficient evidence that thiopurines affect hospitalisation, evidence favours that aTNF therapy probably reduces the risk of hospitalisation within the first year of use, but it is less clear on whether this effect continues beyond this period. More structured research needs to be conducted to answer these clinically important questions

Growing with smart products:Why customization capabilities matter for manufacturing firms

Manufacturing firms that engage in digital transformation develop increasingly smarter versions of their tangible products to reinvigorate growth in shrinking markets. However, they often struggle with translating their investments in digitalization capabilities into actual returns in the form of sales growth. The associated technological advantages often remain unexploited, and digital product innovations frequently fail. Building on the resource-based view of the firm and the demand-side perspective, we theorize that there is a need for complementary capabilities that integrate heterogeneous customer demands, thus, allowing firms to capture more value from smart products. We empirically investigate the mediating role of smart customization capability on the relationship between digitalization capabilities and sales growth. Moreover, we argue that this relationship is further strengthened by integrating information and data across sales and service channels (i.e., channel integration). We test and find support for our hypotheses based on a dataset comprising survey and archival data of 136 smart product manufacturers in Austria, Germany, Switzerland, and the United States. In doing so, we enhance the theoretical understanding of resource and capability configurations needed for digital transformation in general and smart product success in particular. We further update the traditional concept of mass customization by showing how customization with smart products helps manufacturing firms provide personalized solutions at scale

A Gas Generating System for Complex Gas Mixtures – Multifunctional Application in PTR Method Optimization and Downstream Methanol Synthesis

The multifunctional applicability of a gas mixing system is presented within the scope of Carbon2Chem® for the simulation of steel mill flue gases and their application in downstream processes. A special focus is set on the parallel operation of the gas mixing system to enable PTR-MS method optimization and methanol synthesis with simulated real gas matrices. Information is gathered for the design of downstream processes and their application, where methanol synthesis is chosen as a model reaction. A proof-of-principle study is presented where operation of a catalytic reactor setup in combination with the gas mixing system and a compressor generate reproducible results. The addition of potential trace components in methanol synthesis is exemplarily demonstrated using ammonia. With respect to the PTR-MS application, the dosing of two calibration gas standards, toluene and carbonyl sulfide, via the gas mixing system were analyzed in detail. The obtained results give insight into its applicability to simulate traces and enables the further development of analytical methods for the analysis of trace impurities in the ppb and ppt range in complex gas mixtures

Ano-genital Granulomatosis and Crohn's Disease: A Case Series of Males Presenting with Genital Lymphoedema.

Background and Aims: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease and optimal methods of treatment are poorly understood. Methods: A retrospective casenote review of 25 male patients with ano-genital granulomatosis presenting with genital lymphoedema was performed to determine the clinical and histopathological features of this condition and its relationship to intestinal Crohn's disease. Results: A combination of penile and scrotal oedema was reported at presentation in 80% of patients; 40% of patients had associated intestinal Crohn's disease. The average time from symptom onset to diagnosis was 52.7 months. Half of cutaneous biopsies contained non-caseating granulomas and 14% contained intralymphatic granulomas. In all, 72% of patients responded to oral steroids initially but recurrence was common. Complete or partial response was achieved in 60% of patients treated with azathioprine. Three of six patients responded to anti-tumour necrosis factor [TNF] therapy. A small proportion of patients required circumcision or de-bulking surgery for more debilitating disease. Conclusions: Ano-genital granulomatosis is a rare condition that presents with genital lymphoedema, and there is frequently a protracted delay in diagnosis. There is a very strong association with intestinal Crohn's disease. Genital lymphoedema associated with gastrointestinal symptoms should prompt careful evaluation to exclude both ano-genital granulomatosis and Crohn's disease

Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM-1 and HLA-DR/Ia molecules

This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed—HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4+ T cells stimulated by autologous monocytes induced by HBsAg

Combining Donor and Recipient Age With Preoperative MELD and UKELD Scores for Predicting Survival After Liver Transplantation

Objectives: The end-stage liver disease scoring systems MELD, UKELD, and D-MELD (donor age × MELD) have had mediocre results for survival assessment after orthotopic liver transplant. Here, we introduced new indices based on preoperative MELD and UKELD scores and assessed their predictive ability on survival posttransplant. Materials and Methods: We included 1017 deceased donor orthotopic liver transplants that were performed between 2008 (the year UKELD was introduced) and 2019. Donor and recipient characteristics, liver disease scores, transplant characteristics, and outcomes were collected for analyses. D-MELD, D-UKELD (donor age × UKELD), DR-MELD [(donor age + recipient age) × MELD], and DR-UKELD [(donor age + recipient age) × UKELD] were calculated. Results: No score had predictive value for graft survival. For patient survival, DR-MELD and DR-UKELD provided the best results but with low accuracy. The highest accuracy was observed at 1 year posttransplant (areas under the curve of 0.598 [95% CI, 0.529-0.667] and 0.609 [95% CI, 0.549-0.67] for DR-MELD and DR-UKELD). Addition of donor and recipient age significantly improved the predictive abilities of MELD and UKELD for patient survival, but addition of donor age alone did not. For 1-year mortality (using receiver operating characteristic curves), optimal cut-off points were DR-MELD >2345 and DR-UKELD >5908. Recipients with DR-MELD >2345 (P 5908 (P = .002) had worse patient survival within the first year, but only DR-MELD >2345 remained significant after multiva­riable analysis (P = .007). Conclusions: DR-MELD and DR-UKELD scores provided the best, albeit mediocre, predictive ability among the 6 tested models, especially at 1 year after posttransplant, although only for patient but not for graft survival. A DR-MELD >2345 was considered to be an additional independent risk factor for worse recipient survival within the first postoperative year

Comparison of small intestinal contrast ultrasound with magnetic resonance enterography in pediatric Crohn's disease

Aim To compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients investigated for Crohn's disease (CD) attending a UK tertiary center. Methods and Results Patients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD‐related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2–17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68). Conclusions SICUS offers a radiation‐free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice

Chronic abdominal pain in inflammatory bowel disease: a practical guide

Pain is common in inflammatory bowel disease (IBD), yet many patients feel their pain is not addressed by healthcare professionals. Listening to a patient’s concerns about pain, assessing symptoms and acknowledging the impact these have on daily life remain crucial steps in addressing pain in IBD. While acute pain may be effectively controlled by pain medication, chronic pain is more complex and often pharmacological therapies, particularly opioids, are ineffective. Low-dose tricyclic antidepressants and psychological approaches, including cognitive–behavioural therapy, have shown some promise in offering effective pain management while lifestyle changes such as a trial of low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet in those with overlapping irritable bowel syndrome may also reduce pain. Patients benefit from a long-term, trusting relationship with their healthcare professional to allow a holistic approach combining pharmacological, psychological, lifestyle and dietary approaches to chronic pain. We present a practical review to facilitate management of chronic abdominal pain in IBD

Donor-Recipient Body Surface Area Mismatch and the Outcome of Liver Transplantation in the UK

Introduction: Too small or too big liver grafts for recipient's size has detrimental effects on transplant outcomes. Research Questions: The purpose was to correlate donor-recipient body surface area (BSA) ratio or BSA index (BSAi) with recipient survival, graft survival, hepatic artery or portal vein, or vena cava thrombosis. High and low BSAi cut-off points were determined. Design: There were 11,245 adult recipients of first deceased donor whole liver-only grafts performed in the UK from January 2000 until June 2020. The transplants were grouped according to the BSAi and compared to complications, graft and recipient survival. Results: The BSAi ranged from 0.491 to 1.691 with a median of 0.988. The BSAi > 1.3 was associated with a higher rate of portal vein thrombosis within the first 3 months (5.5%). This risk was higher than size-matched transplants (OR: 2.878, 95% CI: 1.292-6.409, P = 0.01). Overall graft survival was worse in transplants with BSAi ≤ 0.85 (HR: 1.254, 95% CI: 1.051-1.497, P = 0.012) or BSAi > 1.4 (HR: 3.704, 95% CI: 2.029-6.762, P 1.4. These findings were confirmed by bootstrap internal validation. No statistically significant differences were detected for hepatic artery thrombosis, occlusion of hepatic veins/inferior vena cava or recipient survival. Conclusions: Donor-recipient size mismatch affects the rates of portal vein thrombosis within the first 3 months and overall graft survival in deceased-donor liver transplants

Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case-control study.

OBJECTIVE: Depression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD. DESIGN: We conducted a nested case-control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn's disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5-5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status. RESULTS: We identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38). CONCLUSIONS: Depression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD