Background Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus (T2D) was a potential risk factor for young‐onset colorectal cancer (YOCRC). Methods The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55. Ninety unrelated YOCRC cases were recruited to the study. Personal history and detailed family history of T2D were obtained at face‐to‐face interview and confirmed from medical records. Whole exome sequencing was conducted on germline DNA from each CRC case. Controls for personal history studies of T2D were 240 patients with proven clear colonoscopies and no known CRC predispositions. Results The median age of YOCRC cases was 44 years (18–54) and of controls was 45 years (18–54), and 53% of both cases and controls were females (P = 0.99). Left‐sided (distal) CRC was seen in 67/89 (75%) of cases. A personal history of T2D was confirmed in 17/90 (19%) YOCRC patients compared with controls (12/240, 5%; P < 0.001; odds ratio = 4.4; 95% confidence interval, 2.0–9.7). YOCRC patients frequently reported at least one first‐degree relative with T2D (32/85, 38%). Ten of 87 (12%) of YOCRC cases had CRC‐related pathogenic germline variants, however, no pathogenic variants in familial diabetes‐associated genes were seen. Conclusions Though the mechanism remains unclear, our observations suggest that there is enrichment for personal history of T2D in YOCRC patients. Impact A diagnosis of T2D could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.
Intravenous immunoglobulin (IVIg), which is used to treat multiple neurological conditions, may be associated with serious adverse reactions. The individual neurological disease characteristics associated with adverse reactions, along with strategies to prevent and treat adverse reactions, are uncertain. A systematic review was conducted of the databases PubMed, Embase, and Cochrane Library to summarise studies that report adverse reactions of IVIg therapy in patients with neurological disease. There were 65 studies included in the review. The reported rates of adverse reactions vary widely, but the best evidence suggests rates between 25 and 34% per patient. Common adverse reactions include headache and laboratory abnormalities. Less common but serious adverse reactions included thromboembolic complications and anaphylaxis. Overall, there is a lack of high-quality comparative data to definitively determine if any specific neurological indications are associated with a higher risk of adverse reactions. However, individual neurological disease characteristics possibly associated with an increased likelihood of adverse reactions include limited mobility (as in certain neuromuscular conditions), paraproteinaemia (as in certain peripheral neuropathies), and cardiomyopathy (as in certain myopathies). There is limited evidence to support the effectiveness of prevention and treatment strategies, which may include modification to dose, reduced infusion rate, and premedication. Further studies regarding methods to prevent and treat IVIg-ARs in neurology patients are required.
Background and Aim The comparative utility of physiological reserve measures in predicting important clinical outcomes following liver transplantation (LT) requires further study. The aim of this work was therefore to compare the utility of physiological reserve measures in predicting early adverse clinical outcomes post‐LT. Methods A single‐center, retrospective cohort study of LT patients consecutively recruited between 1 January 2015, and 31 August 2020. Outcomes measured were sepsis and death within 12 months of LT, hospital length of stay (LOS), and intensive care LOS. Physiological reserve measures were handgrip strength, mid‐arm muscle circumference, and cardiopulmonary exercise testing (CPET) measures. Analysis was performed using univariate and multivariate logistic regression for sepsis and death, and univariate and multivariate Cox regression for hospital and intensive care LOS. Results Data were obtained for 109 subjects. Patients were predominantly (64%) male with a median (interquartile range [IQR]) age of 57 (49–63) and median (IQR) Model for End‐Stage Liver Disease score of 16 (11–21). In multivariate analysis, the odds of sepsis were lower in patients in the highest versus lowest tertile (odds ratio = 0.004; 95% confidence interval [CI] 0.00–0.13; P = 0.002). Hospital LOS was linearly associated with handgrip strength (hazard ratio [HR] = 1.03; 95% CI 1.00–1.06; P = 0.03) in multivariate analysis. Intensive care LOS was associated with peak VO2 (HR 1.83; 95% CI 1.06–3.16; P = 0.03) and VE/VCO2 slope (HR 0.71; 95% CI 0.58–0.88; P = 0.002) in multivariate analysis. Conclusion Handgrip strength and CPET both identify candidates at high risk of adverse outcomes after LT.
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