The Western Health and Social Care Trust is a health organisation in Northern Ireland. Hospitals served by the Trust include Altnagelvin Area Hospital, Tyrone and Fermanagh Hospital, Omagh Hospital and Primary Care Complex and the South West Acute Hospital.
Background:Wiring in bifurcation percutaneous coronary intervention can be limited by severe angulation, adverse plaque biasing, and ostial ambiguity. Real-time intravascular ultrasound (RT-IVUS) guidance can augment wire manipulation when standard techniques fail. Case summary:A 49-year-old man with exertional angina had a critical lesion left anterior descending (LAD)-2nd diagonal bifurcation lesion (Medina 1,1,0) with TIMI 2 flow. Standard wiring (acutely angled wires, dual lumen, and angled microcatheters) repeatedly biased into the diagonal. Under RT-IVUS, the wire was redirected into the true lumen of mid-LAD, enabling lesion crossing, pre-dilatation, and implantation of a 3.5 × 26 mm2 DES with post-dilatation. Final IVUS showed optimal expansion (MSA 9 mm2). The patient was discharged same day; at 3 months, he remained asymptomatic with a patent stent. Conclusion:RT-IVUS can overcome wiring failure in complex bifurcations by providing live intravascular guidance augmenting wire passage into true lumen, supporting safe, efficient revascularization.
BACKGROUND:Vitamin D is a key regulator of musculoskeletal growth, immune regulation, and cognitive function in children. As children in the United Kingdom (UK) and Ireland are at risk of vitamin D deficiency due to the northern latitude, supplementation is recommended. To our knowledge, the effect of supplementation on status and related health outcomes has not been investigated in children residing in the UK/Ireland. OBJECTIVES:To examine the effect of vitamin D3 supplementation on vitamin D status and related health outcomes in children. METHODS:The D vitamin in children study was a double-blind, randomized, placebo-controlled trial, conducted among healthy children (aged 4-11 y). Children received 12 wk of either 10 μg/d vitamin D3 or a placebo devoid of vitamin D (control) in the form of an oral spray. The primary outcome, plasma 25-hydroxyvitamin D, and secondary outcomes, including grip strength, balance, cognitive function, winter status, immune markers, and bone turnover markers, were assessed pre- and postintervention. RESULTS:One hundred eighteen participants completed the study (mean age 8.1 ± 1.8 y; 51% girls). Supplementation significantly increased 25-hydroxyvitamin D concentration (from 66.31 ± 17.26 nmol/L to 69.04 ± 16.93 nmol/L) compared to a decline in the placebo group (63.67 ± 19.48 nmol/L to 56.29 ± 18.58 nmol/L; P < 0.001) and prevented deficiency during the extended winter months. No effects were observed on muscle function, cognitive function, immune function, or bone turnover markers. CONCLUSIONS:Vitamin D insufficiency is prevalent in UK/Irish children, and supplementation in the form of an oral spray is effective in achieving/maintaining an adequate status in most children. Further research is warranted to elucidate mechanisms underpinning nonresponse to supplementation and to further investigate the potential beneficial effects of supplementation on cognitive function. This trial was registered at clinicaltrials.gov as NCT05018988.
Irinotecan, a topoisomerase I inhibitor, is available as both non-pegylated and pegylated formulations. The non-pegylated formulation is licensed for use in advanced colorectal cancer either in combination with other agents or as monotherapy. However, it is also used off-label across a range of gastrointestinal malignancies and in rare malignancies such as glioblastoma and sarcomas. The pegylated formulation is licensed for use as combination therapy in adult patients with metastatic pancreatic adenocarcinoma. Irinotecan is hydrolysed to its active metabolite, SN-38, which is predominantly inactivated by the enzyme uridine diphosphate glucuronosyltransferase UGT1A1. UGT1A1 is encoded by the gene UGT1A1, which is polymorphically expressed, with allele frequencies varying across populations. Poor metabolizers carry two variants that reduce UGT1A1 enzyme expression or activity, leading to increased risk of irinotecan toxicity. Any patient who is about to be prescribed irinotecan for an epithelial malignancy should have pharmacogenetic testing, to identify clinically relevant UGT1A1 variants, where testing is available. Irinotecan dose should be reduced by 30% at Cycle 1 treatment in poor metabolizers for all indications, with doses titrated thereafter based on tolerability and neutrophil counts. The lack of evidence precludes us from making any recommendation for rare malignancies such as sarcomas. Our guideline is consistent with other international pharmacogenetics prescribing guidelines. This guideline is grounded in the latest evidence but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk-benefit profile, ensuring that therapy is optimized to maximize benefits while minimizing potential harms.
Cryoglobulins are proteins that are temperature sensitive, precipitating at temperatures below 37°C, and dissolve upon rewarming. However, at lower temperatures cryoglobulins can result in damage subsequently leading to vascular compromise. We present a case of a patient with a known lymphoplasmacytic lymphoma. The patient developed extensive finger necrosis and toe necrosis. Cryoglobulin was requested and a small type I was found. Given how common type I cryoglobulins are, more evidence was needed that this was the underlying aetiology of the necrosis. A biopsy of the tissue immediately proximal to the necrosis was performed. Histological evaluation confirmed cryoglobulin occlusions. Given the small cryoglobulin level, we assume the thermal amplitude of this resulted in this degree of vascular damage. Thermal amplitude of cryoglobulins is not generally performed. However, we know from testing the thermal amplitude of the red cell agglutination that the more active the antibody is at higher temperatures like those experienced in both the central and peripheral circulation, the more clinically significant the haemolysis. As this lady had chronic stable haemolysis, we sent the sample to the red cell reference lab to investigate the thermal range of the red cell antibody. This was checked at 4°C, room temperature, and 37°C. The cold antibody titre was 65536 at 4°C, 2048 at room temperature, and 1 at 37°C. This activity, despite having large titres at the cold range, demonstrated a wide thermal amplitude. Therefore, given these findings it is likely that the cryoprecipitate within the plasma had a similarly high thermal range.
