Drug-induced liver injury secondary to tamoxifen.

Tamoxifen is a non-steroidal selective oestrogen receptor modulator commonly used in the treatment of breast cancer. It is associated with the development of fatty liver and steatohepatitis however drug-induced liver injury is rare. We report a woman in her 50s who developed malaise with an acute moderate aminotransferase elevation without jaundice 6 months after starting tamoxifen. She was not commenced on any other recent drugs and extensive investigation including infective and autoimmune liver screen, cross-sectional imaging and FibroScan were unremarkable. Liver biopsy revealed moderate lobular hepatitis with hepatocyte drop-out. Tamoxifen was ceased and the liver enzymes showed resolution over the following 3 months and improvement of her symptoms.

Indications and outcomes of transjugular intrahepatic portosystemic shunt insertion in two regional Australian hepatology centres.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. AIMS: The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. METHODS: Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. RESULTS: Forty-eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46-65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre- and post-TIPS were 10 (IQR: 4.5-16) and 2 (IQR: 0-4) respectively (P < 0.001). There were no procedure-related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre-TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post-TIPS (P < 0.001). CONCLUSIONS: TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting.

Mercaptopurine-induced Sweet's syndrome.

Sweet's syndrome is an acute febrile neutrophilic dermatosis. Drug-induced Sweet's syndrome typically occurs soon after drug administration, with rapid resolution of symptoms with cessation of the offending agent. We report a man in his early 40s who presented with fever and widespread erythematous rash on a background of recently diagnosed mild stricturing ileal Crohn's disease. He was commenced on 6-mercaptopurine 12 days before presentation. Skin biopsy demonstrated diffuse infiltration of neutrophils in the upper dermis, dermal oedema, eosinophils and fibrin deposition. Symptoms rapidly improved with cessation of 6-mercaptopurine without requiring systemic corticosteroids.

Inflammatory bowel disease patients have an increased risk of acute coronary syndrome: a systematic review and meta-analysis.

OBJECTIVES: Systemic inflammation is increasingly being recognised as a possible mechanism for acute arterial thrombotic events, including acute coronary syndrome (ACS). Despite this, there is conflicting data on the risk of ACS in patients with inflammatory bowel disease (IBD). We performed a contemporary systematic review and meta-analysis to identify the risk of ACS in patients with IBD. METHODS: PubMed, MEDLINE, EMBASE, CENTRAL and Web of Science were searched up to 27 October 2022. Multivariable-adjusted or propensity matched studies with a non-IBD control cohort were included. HRs were pooled using a random-effects model. Subgroup and sensitivity analyses were conducted in order to explore sources of heterogeneity. RESULTS: Twelve retrospective cohort studies were included (225 248 IBD patients). Patients with IBD were associated with an increased risk of ACS in both adjusted (HR 1.23; 95% CI 1.08 to 1.41) and unadjusted analyses (HR 1.50; 95% CI 1.16 to 1.92). Substantial heterogeneity was observed (i2=88, p=0.002 and i2=98%, p=0.002, respectively). Subgroup analysis of age revealed a greater association of ACS in IBD patients <40 years of age (relative HR 1.50; 95 CI 1.15 to 1.96). CONCLUSION: Patients with IBD demonstrated an independently increased risk of ACS. Prospective studies are required to explore the relationship with disease activity and duration, concomitant medication use and angiographic characteristics and outcomes. PROSPERO REGISTRATION NUMBER: CRD42022367846.

Older adults with acute severe ulcerative colitis have similar steroid non-response and colectomy rates as younger adults.

BACKGROUND: There is paucity of data on outcomes of acute severe ulcerative colitis (ASUC) in older adults (≥ 60 years of age). AIM: To assess steroid non-response rates during the index admission for ASUC in older adults. Secondary outcomes were response to medical rescue therapy and colectomy rates; at index admission, 3 and 12 mo. METHODS: This retrospective multicentre cohort study included ASUC admissions who received intravenous steroids between January 2013 and July 2020 at two tertiary hospitals. Electronic medical records were reviewed to collect clinical, biochemical, and endoscopic data. A modified Poisson regression model was used for analysis. RESULTS: Of 226 ASUC episodes, 45 (19.9%) occurred in patients ≥ 60 years of age. Steroid non-response rates were comparable in older adults and patients < 60 years of age [19 (42.2%) vs 85 (47%), P = 0.618, crude risk ratio (RR) = 0.89 [95% confidence interval (CI): 0.61-1.30], adjusted RR = 0.99 (0.44-2.21). Rates of response to medical rescue therapy in older adults was comparable to the younger cohort [76.5% vs 85.7%, P = 0.46, crude RR = 0.89 (0.67-1.17)]. Index admission colectomy [13.3% vs 10.5%, P = 0.598, crude RR = 1.27 (0.53-2.99), adjusted RR = 1.43 (0.34-6.06)], colectomy at 3 mo [20% vs 16.6%, P = 0.66, crude RR = 1.18 (0.61-2.3), adjusted RR = 1.31 (0.32-0.53)] and colectomy at 12 mo [20% vs 23.2%, P = 0.682, crude RR = 0.85 (0.45-1.57), adjusted RR = 1.21 (0.29-4.97)], were similar between the two groups. CONCLUSION: In older adults with ASUC, the steroid non-response rate, response to medical rescue therapy, and colectomy rate at index admission, 3 and 12 mo is similar to patients less than 60 years of age.

Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response.

OBJECTIVES: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. DESIGN: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015-2020, n=110; All India Institute of Medical Sciences, New Delhi 2018-2020, n=62). RESULTS: In the 2015-2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992-1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992-1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%-11%. CONCLUSIONS: Emergency colectomy rates for ASC have halved in 25 years to 8%-15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.

Vedolizumab-Induced Acute Interstitial Nephritis in Ulcerative Colitis.

Vedolizumab is used in the treatment of inflammatory bowel disease and is generally well tolerated. We report a 20-year-old man who presented with right flank pain on a background of ulcerative colitis. He was on vedolizumab with his last dose 1 week before the onset of symptoms. Kidney function tests revealed a serum creatinine of 171 µmoL/L and a C-reactive protein of 74 mg/L. Kidney biopsy demonstrated focal acute interstitial nephritis. He was prescribed oral prednisolone and achieved complete recovery of renal function within 3 weeks. At the follow-up after 4 months, his renal function remains normal.

Clinical benefits of prolonged dual antiplatelet therapy following complex percutaneous coronary intervention.

AIMS: Prolonged dual antiplatelet therapy (DAPT) requires consideration of both reduced thrombotic events and increased bleeding risk. The associated subtle balance between the benefits and harms depends upon patient's clinical factors and complexity of the coronary anatomy. Our aim was to assess the safety and efficacy of prolonged (>12 months) DAPT in patients undergoing complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: A thorough computer-based search was performed using four major databases. Complex PCI was defined as a procedure with at least one of the following angiographic characteristics: 3 vessels treated, >3 stents implanted, >3 lesions treated, bifurcation lesions, total stent length >60 mm, left main or proximal left anterior descending, a vein graft stent, or chronic total occlusion as target lesion. Of the 3543 titles searched, 5 studies met the inclusion criteria comparing short and prolonged DAPT therapy. We applied a random-effects model to acknowledge the variation in study design, treatment duration, and length of follow-up among studies. There was a reduction in cardiac mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.35-0.92; P = 0.02, I = 0%] and major adverse cardiovascular events (OR 0.76, 95% CI: 0.59-0.96; P = 0.02, I = 22%) with prolonged DAPT. Major bleeding was increased with prolonged DAPT (OR 1.75, 95% CI: 1.20-2.20; P = 0.004, I = 0%). There was no difference in the all-cause mortality (OR 0.86, 95% CI: 0.61-1.22; P = 0.41, I = 0%). CONCLUSION: Prolonged DAPT reduces cardiac mortality and major adverse cardiovascular events in complex PCI. The results would need confirmation in a larger randomized study.

A meta-analysis of randomized controlled trials to compare long-term clinical outcomes of bioabsorbable polymer and durable polymer drug-eluting stents.

AIMS: The durable polymer (DP) of a drug-eluting stent (DES) serves no function once drug elution is complete. To ascertain the benefits of bioabsorbable polymer (BP) over DP-DESs requires a longer follow-up period, to overcome the time taken for polymer absorption. The primary aim of this meta-analysis was to compare the safety and efficacy of BP-DES with the DP-DES over mid (2 years) to long-term (3-5 years) follow-up. METHODS AND RESULTS: A thorough computer-based search was performed using Ovid MEDLINE, EMBASE, Google Scholar, and PubMed databases. We only included randomized controlled studies comparing clinical outcomes between BP-DESs and DP-DESs. Only studies where data were available for a minimum of 2 years were included. A separate analysis of 2-year outcomes and 3- to 5-year outcomes were conducted. Data from 6 and 8 studies were included in 3- to 5-year and 2-year follow-up, respectively. There were no differences between stent groups in cardiac mortality, stent thrombosis (ST), target lesion revascularization, target vessel failure, and reinfarction rates for either 2-year or 3- to 5-year follow-up. Subgroup analysis according to strut thickness (<100 µm, >100 µm) of BP-DES demonstrated similar results. The analyses of ST and very late ST favoured BP-DESs but did not reach statistically significant level. CONCLUSION: There were no differences in clinical outcomes between BP-DESs and DP-DESs over mid- and long-term follow-up.