RhoC expression increases with breast cancer progression and RhoC protein level in tumor tissue is strongly associated with biologically aggressive invasive carcinomas of the breast. RhoC expression, if validated, may identify patients who are less likely benefit from doxorubicin therapy and suggests RhoC overexpression as a new target for intervention.
Frustratingly, disease-modifying treatments for diabetic neuropathy remain elusive. Glycaemic control has a robust effect on preventing neuropathy in individuals with type 1 but not in those with type 2 diabetes, which constitute the vast majority of patients. Encouragingly, recent evidence points to new metabolic risk factors and mechanisms, and thus also at novel diseasemodifying strategies, which are desperately needed. Obesity has emerged as the second most important metabolic risk factor for neuropathy (diabetes being the first) from consensus findings of seven observational studies in populations across the world. Moreover, dyslipidaemia and altered sphingolipid metabolism are emergent novel mechanisms of nerve injury that may lead to new targeted therapies. Clinical history and examination remain critical components of an accurate diagnosis of neuropathy. However, skin biopsies and corneal confocal microscopy are promising newer tests that have been used as outcome measures in research studies but have not yet demonstrated clear clinical utility. Given the emergence of obesity as a neuropathy risk factor, exercise and weight loss are potential interventions to treat and/or prevent neuropathy, although evidence supporting exercise currently outweighs data supporting weight loss. Furthermore, a consensus has emerged advocating tricyclic antidepressants, serotonin-noradrenaline (norepinephrine) reuptake inhibitors and gabapentinoids for treating neuropathic pain. Out-of-pocket costs should be considered when prescribing these medications since their efficacy and tolerability are similar. Finally, the downsides of opioid treatment for chronic, non-cancer pain are becoming increasingly evident. Despite these data, current clinical practice frequently initiates and continues opioid prescriptions for patients with neuropathic pain before prescribing guidelinerecommended treatments.
Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor ≤age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age >44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.
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