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BACKGROUND: Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology and outcomes of acute rejection have not been well-described in Australia. METHODS: We retrospectively studied consecutive adults who underwent deceased-donor LT at a single centre between 2010-2020. Donor and recipient data at time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed and only a graft's first instance of biopsy-proven acute rejection was analysed. RESULTS: During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p=0.11). The median time to first episode of rejection was 71 days post-LT: 2.2% hyperacute, 50.4% early (≤90 d) and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI 0.97-1.00, p=0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI 1.27-5.09, p<0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI 0.08-0.58, p<0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI 2.21-4.42, p<0.001) and patient survival (aHR 3.42, 95% CI 2.35-4.98, p<0.001). CONCLUSION: In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors.
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Summary: Fulminant type 1 diabetes mellitus (FT1DM) is characterised by extremely rapid destruction of pancreatic beta cells. An association between FT1DM and pregnancy has been reported and can lead to unfavourable pregnancy outcomes without timely treatment. We report a case of FT1DM in a pregnancy with gestational diabetes mellitus (GDM), the first of its kind in the English literature to date. A 27-year-old woman with insulin-requiring GDM presented with rapidly deteriorating glycaemic control in her third trimester of pregnancy despite good concordance to treatment. The investigation identified the hallmarks of FT1DM: hyperglycaemia with acute metabolic decompensation and non-immune-mediated beta-cell failure. She received prompt treatment with intravenous insulin therapy and was transitioned to subcutaneous insulin once biochemical improvement had been achieved, albeit with higher insulin requirements than before. She had a good pregnancy outcome and delivered a healthy male infant 5 weeks later through induction of labour. Due to persistent beta-cell dysfunction, she remained on basal-bolus insulin postpartum. This case highlights the importance of early recognition and treatment of FT1DM in pregnancy to prevent adverse maternal and fetal prognoses. Learning points: Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes characterised by extremely rapid beta-cell destruction, leading to abrupt-onset hyperglycaemia with ketosis or ketoacidosis. The pathognomonic characteristics of FT1DM include the development of diabetic ketosis or ketoacidosis typically within 7 days after the onset of symptoms of hyperglycaemia, a near-normal level of glycated haemoglobin despite elevated plasma glucose levels and the absence of islet cell autoantibodies. The pathophysiology of FT1DM is unclear but the association with genetic predisposition, viral infection and pregnancy has been reported. Due to its predilection for pregnancy, clinicians should have a high index of suspicion for FT1DM in pregnant women with rapidly progressing hyperglycaemic ketoacidosis. As diabetic ketoacidosis in pregnancy is associated with adverse maternal and fetal outcomes, immediate initiation of treatment in pregnant women with suspected FT1DM is extremely vital to prevent morbidity and mortality, even if investigations are still underway. Patients with FT1DM require lifelong insulin therapy due to the complete loss of beta-cell function.
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Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians.
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BACKGROUND: The SCCAI was designed to facilitate assessment of disease activity in ulcerative colitis (UC). We aimed to interrogate the metric properties of individual items of the SCCAI using item response theory (IRT) analysis, to simplify and improve its performance. METHODS: The original 9-item SCCAI was collected through TrueColours, a real-time software platform which allows remote entry and monitoring of patients with UC. Data were securely uploaded onto Dementias Platform UK Data Portal, where they were analysed in Stata 16.1 SE. A 2-parameter (2-PL) logistic IRT model was estimated to evaluate each item of the SCCAI for its informativeness (discrimination). A revised scale was generated and re-assessed following systematic removal of items. RESULTS: SCCAI data for 516 UC patients (41 years, SD = 15) treated in Oxford were examined. After initial item deletion (Erythema nodosum, Pyoderma gangrenosum), a 7-item scale was estimated. Discrimination values (information) ranged from 0.41 to 2.52 indicating selected item inefficiency with three items < 1.70 which is a suggested discriminatory value for optimal efficiency. Systematic item deletions found that a 4-item scale (bowel frequency day; bowel frequency nocturnal; urgency to defaecation; rectal bleeding) was more informative and discriminatory of trait severity (discrimination values of 1.50 to 2.78). The 4-item scale possesses higher scalability and unidimensionality, suggesting that the responses to items are either direct endorsement (patient selection by symptom) or non-endorsement of the trait (disease activity). CONCLUSION: Reduction of the SCCAI from the original 9-item scale to a 4-item scale provides optimum trait information that will minimise response burden. This new 4-item scale needs validation against other measures of disease activity such as faecal calprotectin, endoscopy and histopathology.
