ABSTRACT
Sarcopenia, defined as decrease in muscle function and mass, is common in patients with moderate to advanced chronic kidney disease (CKD) and is associated with poor clinical outcomes. Muscle mitochondrial dysfunction is proposed as one of the mechanisms underlying sarcopenia. Patients with moderate to advanced CKD have decreased muscle mitochondrial content and oxidative capacity along with suppressed activity of various mitochondrial enzymes such as mitochondrial electron transport chain complexes and pyruvate dehydrogenase, leading to impaired energy production. Other mitochondrial abnormalities found in this population include defective beta-oxidation of fatty acids and mitochondrial DNA mutations. These changes are noticeable from the early stages of CKD and correlate with severity of the disease. Damage induced by uremic toxins, oxidative stress, and systemic inflammation has been implicated in the development of mitochondrial dysfunction in CKD patients. Given that mitochondrial function is an important determinant of physical activity and performance, its modulation is a potential therapeutic target for sarcopenia in patients with kidney disease. Coenzyme Q, nicotinamide, and cardiolipin-targeted peptides have been tested as therapeutic interventions in early studies. Aerobic exercise, a well-established strategy to improve muscle function and mass in healthy adults, is not as effective in patients with advanced kidney disease. This might be due to reduced expression or impaired activation of peroxisome proliferator-activated receptor-gamma coactivator 1α, the master regulator of mitochondrial biogenesis. Further studies are needed to broaden our understanding of the pathogenesis of mitochondrial dysfunction and to develop mitochondrial-targeted therapies for prevention and treatment of sarcopenia in patients with CKD.
ABSTRACT
Objective: Immunosuppressive drugs, antimicrobial agents and infectious complications may cause liver function test abnormalities [LFTA] in kidney transplant recipients [KTR]. The objectives of this study were to identify the outcome of [LFTA]. To identify the risk factors affecting development and severity of hepatotoxicity in KTR
Methods: We retrospectively evaluated the medical records of KTR. Hepatotoxicity attacks were defined as impairment in liver function tests that was responsive to drug dose reduction or discontinuation, or treatment of specific causes such as infectious complications
Results: One hundred-fifty-six episodes of hepatotoxicity occurred in 107 patients in 281 KTR, with an incidence of 38%. Patients with hepatotoxicity episodes had a high total mortality rate, higher incidence of positive pre-transplant cytomegalovirus [CMV] IgM test, higher creatinine values during the first month post-transplant, underwent additional acute rejection episodes, and received fewer cyclosporin A based ID. Only positive CMV IgM testing was identified as a significant independent risk factor for hepatotoxicity in our multiple analysis. Mycophenolatemofetil [MMF] related hepatotoxicity was the most common cause of drug related LFTA
Conclusions: Patients with LFTA can have significant complications. Pre-transplant positive CMV IgM tests predispose transplant recipients to the development of LFTA during the post-transplant period. MMF can be a serious hepatotoxic drug
ABSTRACT
BACKGROUND: Gastric cancer is one of the most common types of cancer and one of the most frequent causes of cancer-related death. The majority of gastric cancers show distant metastasis at the time of diagnosis. At present, there is no general agreement over one standard chemotherapy regimen for metastatic gastric cancer. AIMS: We evaluated the activity and toxicity of the combination of 5-Fluorouracil (5-FU), epirubicin and cisplatin (FEP) in previously untreated patients with metastatic gastric cancer. SETTING AND DESIGN: Medical Oncology Department of Uludag University Faculty of Medicine, Bursa; retrospective study. MATERIAL AND METHODS: Sixty-eight patients received 5-FU 300 mg/m2 on Days 1-5, epirubicin 50 mg/m2 on Day 1 and cisplatin 60 mg/m2 on Day 1, every 4 weeks. A median of 3.5 cycles was administered. The response rate, time to disease progression, survival and toxic effects were analyzed. STATISTICAL ANALYSIS USED: Overall survival and time to progression were estimated using Kaplan-Meier method. RESULTS: There were 4 partial responses and 1 complete response (overall response rate 7.3%); 16 patients had stable disease. Median progression-free and overall survival rates were 3.1 months (95% CI 1.9-4) and 6 months (95% CI 4.2-7), respectively. The principal toxicity was myelosupression. Grade 3-4 neutropenia occurred in 27.9%, anemia in 17.6%, and thrombocytopenia in 11.7% of patients. Non-hematological toxicity was mild and manageable. CONCLUSIONS: We concluded that FEP combination as used at the doses and schedules in this study has inferior activity against metastatic gastric cancer.