PurposeThe aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients.Patients and methodsA total of 126 patients enrolled in a capecitabine Phase IV clinical trial were analyzed for microsatellite instability (MSI), 18q loss of heterozygosity (LOH), thymidylate synthase (TYMS) 5′ variable number of tandem repeat (VNTR), and methylene tetrahydrofolate reductase (MTHFR) C677T variants. The significance in predicting 5-year DFS/OS was assessed by Kaplan–Meier and Cox regression analyses.ResultsThe MSI-high (MSI-H) genotype was significantly associated with DFS (HR 0.205, 95% CI 0.05–0.88, P=0.033) and OS (HR 0.208, 95% CI 0.05–0.89, P=0.035) compared to the microsatellite stable genotype. In models stratified according to clinicopathologic characteristics, the MSI-H genotype remained a positive predictive factor for DFS/OS only in patients with stage III (P=0.023) and patients with tumors localized proximally to the splenic flexure (P=0.004). Distal colon cancers with 18q LOH have a greater survival rate when treated with capecitabine than patients with stable tumors (81.3% vs 50.0%, HR for relapse 0.348, 95% CI 0.13–0.97, P=0.043). TYMS 5′VNTR and MTHFR C677T variants were not associated with DFS or OS.ConclusionMSI and 18q LOH markers have the potential to be utilized in the selection of colon cancer patients eligible for capecitabine adjuvant monotherapy.

Carnitine palmitoyltransferase II deficiency (CPT II) is an autosomal recessive inherited disorder of long-chain fatty acid oxidation in the mitochondrial matrix, resulting in an inability to utilize fat for energy in cells. The most frequent myopathic form occurs in young adults and is associated with recurrent episodes of exercise-induced rhabdomyolysis. The myopathic form is caused by the Ser113Leu mutation of the CPT II gene. Rarely, massive rhabdomyolysis could be complicated by acute kidney injury (AKI), cardiomyopathy, and respiratory insufficiency. We present a case of an 18-year old male with myalgia, muscular weakness, and dark-colored urine after prolonged exercise and a recent mildSARS-CoV-2infection. Massive rhabdomyolysis was diagnosed with markedly increased serum concentrations of myoglobin and creatine kinase, with normal kidney function. The patient experienced two similar episodes in the years 2017 and 2018, with rhabdomyolysis and AKI treated with hemodialysis. After excluding autoimmune and infectious diseases as causes of recurrent rhabdomyolysis, the patient was genetically tested and Ser113Leu mutation of the CPT II gene was confirmed. When a patient presents with myalgia and dark-colored urine triggered by minor physical activities, genetic testing for possible CPT II deficiency should be initiated. TheSARS-CoV-2infection could be a factor that triggers the occurrence of rhabdomyolysis and aggravates the severity of the attack in patients with CPT II deficiency.

AimsThe present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients.MethodsWe screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57–66 years), and 55% were females.ResultsThe median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06).ConclusionThe AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.

Background The treatment of acute coronary syndrome (ACS) includes dual antiplatelet therapy (DAPT) comprising of aspirin and a P2Y12 inhibitor; clopidogrel is usually the P2Y12 inhibitor of choice in patients with ACS. However, its efficacy has been questioned because of the relatively high incidence of Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) among ACS patients despite adherence to clopidogrel-DAPT. Several risk factors for MACCE following intervention in ACS patients have been described, among others, mutations in the CYP2C19 gene, a member of the cytochrome P450 (CYP450) network. The CYP2C19 enzyme is involved in the metabolism of clopidogrel Interindividual response variability to clopidogrel-DAPT and the increased risk for MACCE have been strongly linked to the CYP2C19*2 and CYP2C19*3 loss-of-function (LOF) allelic variants. Nonetheless, the known CYP2C19 polymorphisms fail to account for all adverse events related to clopidogrel insensitivity. Recent studies point to a putative role of the AKR1D1 gene as a trans-genetic regulator of the CYP450 network. The AKR1D1*36 (rs1872930) minor allelic variant was shown to augment hepatic CYP450 mRNA expression, consequently, increasing the CYP2C19 enzyme activity. To this end, we hypothesise that the AKR1D1*36 polymorphism contributes to the observed incidence of MACCE during clopidogrel antiplatelet therapy. Purpose To determine the association between the AKR1D1*36 (rs1872930) allele and MACCE in Acute Coronary Syndrome (ACS) patients on clopidogrel-DAPT Methods We evaluated 198 consecutive ACS patients indicated for coronary angiography from October to November 2010. We performed a 5-year retrospective medical record review and screened for AKR1D1 and CYP2C19 polymorphisms; 118 patients had a complete medical history and were included in the study. The study participants were prospectively followed for five years or until the first incidence of MACCE. The Median follow up time was 38.5 months (IQR 24–48 months) Results The median age of the cohort was 62.5 years (IQR 57–66), and 55% were females. Follow-up was complete, there were no mortality cases. ACS patients carrying the AKR1D1*36 had a significantly shorter event-free-survival compared to wildtype patients, Hazard Ratio = 2.193 [CI95% 1.091 to 4.406], p=0.0155 (Figure 1). Median time-to-event was 36 months. Evaluation of additional candidate risk predictors in a Cox Proportional Hazards Model confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 additional risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), a history of Myocardial Infarction, HR = 2.62; (95% CI, 1.48 to 4.64), at baseline and presence of the CYPC19*2 allele (HR = 2.33; 95% CI, 1.33 to 4.06). Figure 1. Time-to-Event curve of MACCE Conclusions The AKR1D1*36 (rs1872930) minor variant allele is independently associated with a higher risk for MACCE. Acknowledgement/Funding None

IntroductIon: The cervical uteri cancer (CUCa) continues being an economic, social burden. Represents the second most common women's cancer death. In developing countries CUCa presents in loco-regional advanced stages (Ib2-IIB), and it is treated with the NCCN guidelines that recommend concurrent Radiotherapy/ Chemotherapy (pRT/CT) as primary treatment. These is the most effective treatment, with an effectiveness of 57-87% in stage Ib2. These is reduced to 66% in IIB stages. The role for surgery in IB2-IIB is controversial. Asian and some European groups use surgery as primary treatment in those stages, and could be an effective alternative in developing countries. objectIves: Cost-effectiveness model to compare the performance of the pRT/CT, the Total Mesometrial Resection (TMMR) and the current treatment used in a Public-Health Institution. Methods: 167 cases of CACu patients with clinical stages IB2-IIB in a five-year period were studied. Clinical data, costs of attention, treatment and relapses were obtained from medical charts and micro-costing. Effectiveness was calculated from survival free relapse percentage to five years (0.81, 0.76, 0.68, 0.52, 0.56). The costs for pRT/CT and TMMR alternatives were simulated based on costs obtained from de Diario Oficial de la Federación and from the Instituto Mexicano del Seguro Social web sites. For the pRT/CT and the TMMR treatments effectivity rates were obtained from published data (0.7 and 0.9 respectively). The standard of treatment was the pRT/CT against which we compared the TMMR and the current treatment (CuT) used at our institution. All the costs were expressed in USD results: