Management of the Rectal Stump after Subtotal Colectomy Operations for Inflammatory Bowel Disease in the Era of Immunologic Therapy: A Two-Centre Cohort Study.

INTRODUCTION: Inflammatory bowel disease (IBD) often requires surgical resection, such as subtotal colectomy operations to alleviate symptoms. However, IBD also has an inherently increased risk of colorectal dysplasia and cancer. Despite the well-accepted surveillance guidelines for IBD patients with an intact colon, contemporaneous decision-making models on rectal stump surveillance is sparse. This study looks at the fate of rectal stumps in IBD patients following subtotal colectomy. METHODS: This is a two-centre retrospective observational cohort study. Patients were identified from NHS Grampian and NHS Highland surgical IBD databases. Patients that had subtotal colectomy between January 01, 2010 and December 31, 2017 were included with the follow-up end date on April 1, 2021. Socio-demographics, diagnosis, medical and surgical management data were collected from electronic records. RESULTS: Of 250 patients who had subtotal colectomy procedures, only one developed a cancer in their rectal stump (0.4%) over a median follow-up of 80 months. A higher than expected 72% of patients had ongoing symptoms from their rectal stumps. Surveillance was varied and inconsistent. However, no surveillance, flexible sigmoidoscopy, or MRI identified dysplastic or neoplastic disease. CONCLUSION: Based on our results, we estimate that the prevalence of rectal cancer is lower than previously reported. Surveillance strategy of rectal stump varied as no current guidelines exist and hence is an important area for future study. Given the relatively low frequency of rectal cancer in these patients, and the low level of evidence available in this field, we would propose a registry-based approach to answering this important clinical question.

Sublingual immunotherapy vs placebo in the management of grass pollen-induced allergic rhinitis in adults: A systematic review and meta-analysis.

INTRODUCTION: Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa affecting approximately 20% of the population worldwide. Current therapies include intranasal antihistamines, corticosteroids, subcutaneous and sublingual immunotherapy (SLIT). This review and meta-analysis assess the efficacy of SLIT in the management of grass pollen-induced AR in adults. METHODS: Ovid EMBASE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, Ovid MedLine and PubMed were searched using the following terms: 'sublingual immunotherapy', 'SLIT', 'rhinitis', 'allergic rhinitis', 'rhinosinusitis' and 'rhino-conjunctivitis'. All included studies were double-blind, placebo-controlled and randomised trials. Primary outcome was symptom score and secondary outcome included quality of life and safety profile. Meta-analysis of symptom improvement was carried out. RESULTS: Six studies were identified with 979 subjects randomly allocated to SLIT and 992 to a placebo control. All studies reported an improvement in symptoms with SLIT, with five reaching statistical significance (P < .05). Four studies reported statistically significant improvement in quality of life (P < .05). Oral pruritus was the most common adverse event reported. The overall risk of bias was high in 50% of the studies. CONCLUSIONS: Sublingual immunotherapy was a safe and effective treatment for grass pollen-induced AR in adults, and therefore, consideration should be given to its use for moderate-to-severe disease in the UK-wide population.

Targeting a critical step in fungal hexosamine biosynthesis.

Aspergillus fumigatus is a human opportunistic fungal pathogen whose cell wall protects it from the extracellular environment including host defenses. Chitin, an essential component of the fungal cell wall, is synthesized from UDP-GlcNAc produced in the hexosamine biosynthetic pathway. As this pathway is critical for fungal cell wall integrity, the hexosamine biosynthesis enzymes represent potential targets of antifungal drugs. Here, we provide genetic and chemical evidence that glucosamine 6-phosphate N-acetyltransferase (Gna1), a key enzyme in this pathway, is an exploitable antifungal drug target. GNA1 deletion resulted in loss of fungal viability and disruption of the cell wall, phenotypes that could be rescued by exogenous GlcNAc, the product of the Gna1 enzyme. In a murine model of aspergillosis, the Δgna1 mutant strain exhibited attenuated virulence. Using a fragment-based approach, we discovered a small heterocyclic scaffold that binds proximal to the Gna1 active site and can be optimized to a selective submicromolar binder. Taken together, we have provided genetic, structural, and chemical evidence that Gna1 is an antifungal target in A. fumigatus.