Significant Higher Risk Research Articles

Abstract 183: Outcomes for Major Trauma Patients in Counties Without Trauma Centers Are Worse: Nationwide Population-Based Research in Taiwan

Background: Some articles proved indirect-transfer the major trauma patients to the trauma centers had non-significant different outcomes with the patients direct-transfer to the centers. But the outcomes for the major trauma patients in the counties without trauma centers still can be worse. So we did a population based research by using the NHIRD data for the results. Methods: From the claim data of one million beneficiaries of Taiwan National Health Insurance during the year of 2006 to 2008, all of the trauma patients were identified from the database by the ICD-9-CM system. ICDMAP-90 was used for calculating the Injury Severity Score (ISS) as the variable controlling the disease severity. The patients of major trauma were defined as ISS more than fifteen. We used the diagnosis one year before the trauma admission for calculating Charlson Comorbidity Index (CCI). The first hospitals and the second transferred hospitals that the major trauma patients admitted, and the areas of the first hospitals were recognized in our data bank. The condition of transfer, age, genders, intubation, ICU admission, ISS, CCI, and the triage classifications were adjusted in a logistic regression model for further analysis. Results: There were 2497 major trauma patients (ISS more then 15). The total mortality rate was 12.49%. The variables like age, intubation, ICU admission, ISS and CCI were significant for mortality, but the condition of transfer was not significant in our model. After controlling all the factors, the major trauma patients that first admitted in the areas with no trauma centers have a significant higher risk of mortality (OR=1.73, P=0.005). Conclusions: Our results hint that, although indirect-transfer for the major trauma patients have insignificant difference in mortality with the direct transfer patients, the counties with no trauma centers have significant higher mortality rates in major trauma patients. Further researches are needed for investigating the possible reasons.

Can You Help When It Hurts? Dogs as Potential Pain Relief Stimuli for Children with Profound Intellectual and Multiple Disabilities

Dear Editor, As it is widely recognized, individuals with profound intellectual and multiple disabilities (PIMDs), who are characterized by severe or profound motor disabilities combined with profound cognitive and sensory impairments [1], are at a significant high risk of pain from many sources, including daily care activities, medical procedures, and illness (e.g., [2,3]). Among the nonpharmacological interventions that have already been proposed for alleviating pain in individuals with significant neurologic impairments, increasing attention is currently being devoted to animal-assisted therapy (AAT) programs as effective pain relief interventions [4]. In this letter, we report first experimental data on the potential of therapy dogs as pain relief stimuli for children with PIMD. Given the lack of literature on AAT programs specifically developed for these individuals, we consider that the results here presented may constitute a promising platform to support further investigations. An exploratory study—approved by the Ethics Committee of the O'Porto University—was conducted aiming at assessing, in two children with PIMD, apparent pain relief induced by contact with a therapy dog immediately after a potentially painful care moment. Given the highly limited communication repertoire of the participants (and of children with PIMD in general), only behavioral (following Putten and Vlaskamp [3] and Green and Reid [5]) and heart rate (following Corff et al. [6]) measures were used to estimate pain levels. As to offer a comparison to pain alleviation that might be achieved through maternal touch, responses of the participants to contact with their mothers were …

Genetic Variants in miRNAs Associated with Renal Cell Carcinoma (RCC) Risk: A Pilot Study in North Indian Population

Renal cell carcinoma (RCC) is a leading cause of cancer mortality. Characterizing miRNA expression in RCC by targeting pathways involved in the action of miRNAs, may lead to discovery of some novel prognostic as well as diagnostic biomarkers. In the present study, we aimed at finding the association of various aberrations in miRNAs to be associated with risk of RCC. In this study we selected 100 histologically confirmed RCC patients and 225 healthy unrelated controls with frequency matched age and sex. Genotyping was done by PCR-RFLP for hsa-mir-146aG/C, hsa-mir-27aA/G, hsa-mir-196a2C/T, hsa-mir-499A/G. However, hsa-mir-125aG/T was genotyped by allelic discrimination Taqman® assay. Statistical logistic regression and genetic model was used to find out the genetic effects on the risk of RCC and interactions between polymorphism of all four miRNAs and risk factors. The SNP hsa-mir-196aC/T demonstrated significant high risk for heterozygous genotype (CT; p < 0.001, OR = 3.206, 95 % CI 1.882–5.462) and variant genotype (TT; p = 0.021, OR = 3.57, 95 % CI 1.209–10.54). Similar pattern was seen in the dominant model (CT+TT; p < 0.001, OR = 2.992, 95 % CI 1.798–4.978) with similar effects at allelic level, T allele (p < 0.001, OR = 1.902, 95 % CI 1.335–2.709) also for hsa-mir-196aC/T. In case of hsa-mir499T/C SNP, when the three genotypes were compared, the heterozygous genotype (TC) was found to be associated (p = 0.026, OR = 1.61, 95 % CI 1.05–2.45) with RCC risk. Whereas, hsa-mir27aA/G and hsa-mir146aC/G revealed reduced risk to RCC. Our results suggested that the hsa-mir196a2C/T and hsa-mir499T/C perhaps could be used as a predictive marker for RCC in North Indian population if further validated functionally with varied ethnicities.

Replicative study of GWAS TP63C/T, TERTC/T, and SLC14A1C/T with susceptibility to bladder cancer in North Indians

ObjectiveGenome-wide association studies have confirmed association of TP63C/T rs710521, TERTC/T rs2736098, and SLC14A1C/T rs17674580 gene variants with susceptibility to bladder cancer (BC) in European and White population. However, the risk conferred for BC for above gene variants in North Indians is unknown. We therefore, studied the association of TP63C/T, TERTC/T, and SLC14A1C/T single nucleotide polymorphisms (SNPs) with a risk of BC susceptibility in North Indian cohort. Material and methodsIn histologically confirmed 225 BC cases and 240 healthy controls, 3 SNPs were genotyped by real-time polymerase chain reaction. To evaluate the SNP effects on BC susceptibility, odds ratio (OR) and CI 95% were calculated. ResultsIn case of TP63C/T, the variant genotype (TT) showed significant reduced risk for BC (P = 0.045, OR = 0.53). Combining heterozygous and variant genotypes also demonstrated reduced risk for BC (P< 0.001, OR = 0.54). In case of TERTC/T, heterozygous genotype (CT) as well as variant genotype (TT) showed significant risk for BC susceptibility (P = 0.031, OR = 1.77 and P = 0.004, OR = 2.78, respectively) along with T allelic level (P<0.001, OR = 4.19). Furthermore, in case of SLC14A1C/T gene polymorphism, the variant genotype (TT) showed significant high risk for BC susceptibility (P = 0.006; OR = 3.01) along with variant T allelic level (P = 0.003, OR = 1.52). Interestingly, smoking was also found to modulate risks for BC in case of TERT and SLC14A1 variant genotype (TT). Further clinical confounding factor, namely, tumor grade/stage level of cases, supports the genotypic data with TERT and SLC14A1 showing a risk for BC susceptibility. ConclusionOur results suggested that polymorphism in TERTC/T and SLC14A1C/T confirmed high risk for BC in North Indian population. However, TP63C/T showed reduced risk of BC susceptibility. More replicate studies with large sample size and diverse ethnicity are required to validate these observations.

Risk of pediatric celiac disease according to HLA haplotype and country: evidence-based-medicine viewpoint.

This multi-centric cohort study [1] from four countries followed a group of infants with the HLA haplotype DR3-DQ2 or DR4-DQ8, from birth through the first few years of life; seeking the appearance of antibodies to tissue transglutaminase (tTG) (labeled as celiac disease autoimmunity), and development of celiac disease. This was part of a larger study evaluating the development of type 1 diabetes in a cohort of infants with genetic susceptibility (based on carrying the HLA haplotype DR3-DQ2 or DR4-DQ8) [2]. Over a median follow-up duration of nearly five years, the investigators reported 12% prevalence of celiac disease autoimmunity and 3% prevalence of celiac disease. They also identified that the respective risks of these two outcomes varied by the HLA genotype: 26% and 11% with homozygosity for DR3-DQ2 haplotype; 11% and 3% with DR3-DQ2/DR4-DQ8 haplotype; 8% and 3% with DR4-DQ8 homozygosity; and 3% and <1% among those with DR4-DQ8/DR8-DQ4 haplotype. There was statistically significant higher risk of celiac disease autoimmunity and celiac disease in infants from Europe (highest risk in Sweden), female gender, and those with family history of celiac disease.

Association of genetic polymorphisms in IL-6 and IL-1β gene with risk of lung cancer in female non-smokers

背景与目的白介素-6(interleukin-6, IL-6)和白介素-1β(IL-1β)是白介素家族中具有多功能生物活性的细胞因子。IL-6-634(rs1800796)和IL-1β-31(rs1143627)分别是IL-6基因和IL-1β基因上的两个常见多态位点, 本研究旨在探讨IL-6-634位点和IL-1β-31位点单核苷酸多态性与非吸烟女性肺癌易感性的关系, 并探讨环境危险因素与基因多态性交互作用对肺癌发病风险的影响。方法采用病例-对照研究方法, 纳入非吸烟女性肺癌患者363例和对照370例。采用χ2检验比较各基因型、相关危险因素暴露在病例与对照之间分布的差异, 以比值比(odds ratio, OR)及其95%可信区间(confidence interval, CI)表示相对危险度。采用非条件Logistic回归分析多态基因型与肺癌间相关性及其与危险因素的交互作用。结果IL-6-634位点携带CG基因型的个体发生肺癌危险升高(OR=1.61, 95%CI:1.19-2.19), CG或GG型携带者患肺癌的风险明显高于CC型的携带者(OR=1.48, 95%CI:1.10-1.98);IL-1β-31位点携带CT或TT型的个体肺癌的发病风险要低于CC携带者, 但差异无统计学意义。与携带IL-6-634 CC基因型且无油烟暴露者相比, 既有油烟暴露同时携带CG或GG基因型的个体发生肺癌的危险升高(OR=2.45, 95%CI:1.54-3.90), 而与携带CC型且无结核病史者相比, 既有结核病史并且携带CG或GG基因型的个体发生肺癌的危险升高(OR=2.44, 95%CI:1.05-5.66)。结论IL-6-634基因多态性与非吸烟女性肺癌易感性相关且与油烟暴露和结核病史同时存在能增加患癌风险。

Treatment of HCV infection with the novel NS3/4A protease inhibitors

HCV NS3/4A serine protease inhibitors are the first class of direct acting antivirals (DAA) introduced in clinical practice. The first generation agents, selective against HCV genotype 1, are used in association with pegylated interferons and ribavirin allowing increased cure rates at the price of increased toxicity, significant drug interactions and high risk of selecting mutants conferring cross-resistance to the entire class. A large number of second-wave HCV protease inhibitors are currently in clinical development. Advancements include higher potency, activity against a wider number of genotypes, improved tolerability, easier dosing schedules, although their genetic barrier to resistance remains low, especially for subtype 1a, except for the most recent grazoprevir and ACH-2684. The most relevant progress regards the combination with other classes of DAA allowing construction of interferon-free regimens of short duration, good tolerability with exceptionally high cure rates.

Genome‐wide association study of nevirapine hypersensitivity in a malawian HIV‐infected population

The non-nucleoside reverse transcriptase inhibitor nevirapine is used in the treatment of HIV in many developing countries. Its use is associated with occurrence of hypersensitivity in 6-10% of patients. This hypersensitivity can manifest as a number of phenotypes which include the severe skin blistering reactions Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The aim was to undertake a genome wide association study (GWAS) in order to identify genetic variants associated with predisposition to nevirapine-induced hypersensitivity. A total of 333 nevirapine-exposed (151 hypersensitive and 182 tolerant) , HIV-infected Malawian adults were genotyped for 826,551 genotyped SNPs using the Illumina HumanOmni1-Quad_v1 chip. A replication cohort of 62 hypersensitive and 59 tolerant patients from Malawi and Uganda was genotyped for 40 SNPs statistically significantly associated with a hypersensitive phenotype in the main cohort (p<5x10-5) using the Sequenom iPLEX platform or TaqMan allelic discrimination. Logistic regression analysis identified 40 statistically significant SNP signals associated with a nevirapine hypersensitivity phenotype. Only 1 SNP association signal (in the HLA-C locus, associated with SJS/TEN) was statistically significant in both our main discovery (=1.48x10-6) and enriched replication cohort (38 cases and 59 controls) (p=9.6x10-5). Meta-analysis determined the odds ratio as 5.17 (p=2.61x10-10). Data suggest this SNP to be a strong proxy for HLA-C*04:01 carriage (96% co-occurrence). We have confirmed that, in a sub-Saharan African population, HLA-C*04:01 carriage confers a significant risk for nevirapine-induced SJS_TEN though not to less severe hypersensitivity phenotypes. No other significant high penetrance genetic risk factors were identified.

The incidence and risk factors of meningitis after major craniotomy in China: a retrospective cohort study.

BackgroundMeningitis after neurosurgery can result in severe morbidity and high mortality. Incidence varies among regions and limited data are focused on meningitis after major craniotomy.AimThis retrospective cohort study aimed to determine the incidence, risk factors and microbiological spectrum of postcraniotomy meningitis in a large clinical center of Neurosurgery in China.MethodsPatients who underwent neurosurgeries at the Department of Neurosurgery in Huashan Hospital, the largest neurosurgery center in Asia and the Pacific, between 1stJanuary and 31st December, 2008 were selected. Individuals with only shunts, burr holes, stereotactic surgery, transsphenoidal or spinal surgery were excluded. The complete medical records of each case were reviewed, and data on risk factors were extracted and evaluated for meningitis.ResultsA total of 65 meningitides were identified among 755 cases in the study, with an incidence of 8.60%. The risk of meningitis was increased by the presence of diabetes mellitus (odds ratio [OR], 6.27; P = 0.009), the use of external ventricular drainage (OR, 4.30; P = 0.003) and the use of lumbar drainage (OR, 17.23; P<0.001). The isolated microorganisms included Acinetobacter baumannii, Enterococcus sp, Streptococcus intermedius and Klebsiella pneumonia.ConclusionsMeningitis remains an important source of morbidity and mortality after major craniotomy. Diabetic patients or those with cerebral spinal fluid shunts carry significant high risk of infection. Thus, identification of the risk factors as soon as possible will help physicians to improve patient care.

Percutaneous heart valves; past, present and future

Percutaneous heart valves provide a promising future for patients refused surgery on the grounds of significant technical challenges or high risk for complications. Since the first human intervention more than 10 years ago, over 50 different types of valves have been developed. The CoreValve and Edwards SAPIEN valves have both experienced clinical trials and the latter has gained FDA approval for implantation in patients considered inoperable. Current complications, such as major vascular bleeding and stroke, prevent these valves from being commonly deployed in patients considered operable in conventional surgery. This review focuses on the past and present achievements of these valves and highlights the design considerations required to progress development further. It is envisaged that, with continued improvement in valve design and with increased clinical and engineering experience, percutaneous heart valve replacement may one day be a viable option for lower-risk operable patients.

Safety and efficacy of addition of VEGFR and EGFR-family small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: A meta-analysis.

415 Background: The approach of combining cytotoxic chemotherapy with small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a diverse range of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. Methods: PubMed and the ASCO databases were searched up to March 2013. Eligible studies included randomized trials in which the FDA approved TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR), with corresponding 95% confidence intervals (CI) were calculated. Results: A total of 16,011 patients from 43 trials were included. Among the 43 trials, ten met their primary efficacy endpoints. Among the 21 phase III trials, two led to Food and Drug Administration approval for the combination. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). Compared with chemotherapy alone, the addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). Chemotherapy plus TKI was also associated with a significant higher risk of seven of the 11 evaluated individual AEs: neutropenia (RR, 1.18; P =.004), thrombocytopenia (RR, 1.70; P &lt;.001), febrile neutropenia (RR, 1.48; P &lt;.001), hypertension (RR, 3.01; P &lt;.001), skin toxicities (RR, 6.38; P &lt;.001), diarrhea (RR, 2.57; P =.002) and fatigue (RR, 1.35; P &lt;.001). Conclusions: The addition of a VEGFR or EGFR-family TKI to chemotherapy in solid cancers increases the risk of severe toxicities and treatment discontinuations. These findings might explain the general lack of a survival benefit with these regimens.

The differences in perception of radiological risks: lay people versus new and experienced employees in the nuclear sector

This paper studies the differences in perception of two radiological risks – an accident at a nuclear installation and medical X-rays – between four different groups: the general population without (1) and with experience related to radiological risks (2), new employees (3) and professionally exposed people (4) in the nuclear sector. More precisely, this study determines if differences in risk perception can be explained by the level of experiences with ionizing radiation, the knowledge level about radiological risks, the confidence in authorities, the attitude towards nuclear energy, the trust in a management of nuclear installations, gender and age. The data are gathered using computer assisted personal interviews based on the SCK-CEN Barometer of the Belgian Nuclear Research Centre. The relations between risk perception and the independent variables are tested with linear regression analysis. The risk perception of both risks differs significantly between the four population groups. The professionally exposed people and the new employees in the nuclear sector have a significant higher risk perception for medical X-rays compared to the risk for an accident at a nuclear installation. For the general population without experience, it was just the opposite. The general population with experience does not have a significant difference in risk perception between the two radiological risks. Level of experiences with ionizing radiation is determined as an important variable; people have a lower perception of radiological risks when they have higher experiences with risk.

Birth Defects in Assisted Reproductive Technology and Spontaneously Conceived Children: A Meta-analysis

Objective To evaluate the risk of birth defects in children born following assisted reproductive technology (ART) and spontaneous conceptions. Methods This study carried out an updated systematic review to identify papers published by August 2013 with data relating to birth defects of children conceived using ART (IVF and/or ICSI) compared with those spontaneously conceived and also compared birth defects between subgroups of IVF and ICSI. Results Totally 76 studies were identified for review. The individual relative risk (RR) estimated for these studies ranged from 0.44 to 5.51, a significantly increased risk of birth defects was observed (RR=1.36, 95%CI=1.25–1.47) in ART compared with the spontaneously conceived group, which was also evident in the subgroup analysis. Among these studies, 16 studies simultaneously gave data of birth defects comparing IVF and ICSI children, which showed no difference in risk of combined effects (RR=0.90, 95%CI=0.80–1.02), but ICSI had a higher risk in subgroups of clinical research (RR=0.76, 95%CI=0.65–0.89) and crude RR value (RR=0.78, 95%CI=0.67–0.91). Conclusion Pooled results from all suitable published studies suggested that children born following ART were at increased risk of birth defects compared with spontaneous conceptions. There is no difference in birth defect risk between children conceived by IVF or ICSI using a summative analysis, however, ICSI had a significant higher risk in birth defect risk comparing with IVF when using subgroup analyses of sample size and RR value.

Inhalant substance abuse among adolescents in Manipur, India: An upcoming issue

BACKGROUND: Inhalant use, an important, yet-under recognized form of substance abuse has been reported commonly among adolescents in India but the true extent of the problem is not known due to paucity of data. Aims: To assess the prevalence and determinants of inhalant substance used amongst the adolescents in Manipur. Settings and Design: This cross sectional study was conducted among 1671 adolescent studying in Eighth to Twelfth standard in schools of Imphal-East District Manipur, India during March to June 2013. MATERIALS AND METHODS: Schools were selected by simple random method and a semi-structured self-administered questionnaire adapted from the 'UNDCP/WHO Global initiative on Primary Prevention of substance abuse' was used for data collection. Univariate and Multiple logistic regression analysis were performed for association between ever users and selected variables. RESULTS: Mean (SD) age of the students was 14.5(1.32) years, with males constituting 923(55.2%). Prevalence of ever users was186 (11.1%) and glue/dendrite was the commonest substance abused 98(52.7%). Being male, belonging to joint family and increase in age were found to have significant higher risk of being a user, whereas higher level of parental education shows a protective effect. CONCLUSION: An increased effort for prevention, treatment along with sensitization of parents and teachers is a distinct challenge for policy makers. Language: en

Safety and Tolerability Profile of Artemisinin-Based Antimalarial Combination Therapy in Adult Patients in Benin City, Nigeria

The WHO in 2001 advocated artemisinin- based antimalarial combination therapy (ACT), which was adopted by Nigeria in 2005. The objective of this study was to characterize the safety and tolerability profile of the ACTs in adult patients with uncomplicated malaria. A descriptive longitudinal study was conducted in the General Practice Clinic–of the University of Benin Teaching Hospital (UBTH) and the Central Hospital, Benin City, South-South Nigeria, between October 2009 and March 2010. Adult patients (e”18years) with a diagnosis of uncomplicated malaria and treated with ACTs were recruited for the study. The safety and tolerability profile of ACTs amongst the treated patients were assessed after 9 days of follow up via telephone calls. Adverse Events were classified using the WHO causalityassessment. Five hundred patients were enrolled for this study – Artemether/Lumefantrine (AL) (179), Artesunate/Mefloquine (AM) (149), Artesunate/Amodiauine (AA) (134) Artesunate/Sulphadoxine/Pyrimethamine (ASP) (22), Dihydroartemisinin/ Piperaquine (DP) (16). The mean age of the respondents was 32.6years (range 18-68yrs). One hundred and eighty-eight (37.6%) of the total number of patients followed up reported at least one Adverse Events: 61% in the AA, 60% in the AM, 58% in the AL, 31% in DP, 4 of 19 (21.1%) in ASP. AA treatment was associated with a significant higher risk of gastrointestinal symptoms, dizziness and pruritus than AL and AM (p<0.05). Those treated with AM had a higher incidence of generalized weakness. Ten of the respondents discontinued therapy due to Adverse events experienced: AM (4), AA (4), AL (1), DP (1). Severe AEs were observed in two of these pateints that were given AA and AM respectively. The safety and tolerability of artemetherlumefantrine (AL) and dihydroartemisinin piperaquine (DP) was confirmed in this study. The other recommended ACTs (artesunate-amodiaquine (AA) and artesunate mefloquine (AM) although safe, were less well tolerated and this may affect patients’ adherence with its attendant consequences. Keywords: Artemisinin-based Combination therapy, Adverse Events, Malaria

アレルギー性鼻炎重症例に対するアルゴンプラズマ鼻粘膜焼灼術の治療効果

OBJECTIVES: Argon plasma coagulation (APC), performed as an outpatient procedure, is used to treat severe allergic rhinitis (AR) that is unresponsive to drug therapy. The purpose of this study was to determine the therapeutic effects of APC on patients with perennial AR (PAR) or seasonal AR (pollinosis), and to confirm complications after APC. METHODS: We performed bilateral APC under local anesthesia on 387 patients with PAR or Japanese cedar pollinosis at our clinic between November 2007 and August 2012. Postoperative changes in nasal symptoms including sneezing, nasal discharge and nasal obstruction, and intranasal findings were evaluated using a visual analogue scale (VAS) and the nasal grading score respectively, according to the Practical Guidelines for the Management of Allergic Rhinitis in Japan in 2013. RESULTS: In patients with PAR, the mean VAS scores of nasal symptoms improved in 6 months after APC. The severity of RAST scores to house dust, cauterized level, and nasal septum deviation did not show significant influence on the improvement of nasal obstruction after APC. In patients with pollinosis, the mean VAS score of nasal symptoms showed an improvement of 40-60% for one season after APC. Our data also indicated that the most proper time for APC in seasonal AR was for 2 months before the pollen dispersion. As regards to major postoperative complications, atrophy of the inferior turbinate (8%) and epistaxis (3%) were observed. The patients more than 40 years old and/or with RAST scores less than class 3 to house dust were found as significant high risk factors of inferior turbinate atrophy after APC. CONCLUSIONS: These results indicated that the APC is a useful treatment for patients with AR.

Single Nucleotide Polymorphisms in the Metastasis-associated in Colon Cancer-1 Gene Predict the Recurrence of Hepatocellular Carcinoma after Transplantation

Background: The newly identified metastasis-associated in colon cancer-1 (MACC1) gene is involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), invasiveness, and metastasis in a variety of malignancies. Overexpression of MACC1 gene is a prognostic marker for poor outcome of hepatocellular carcinoma (HCC) patients. However, the association between genetic polymorphisms of MACC1 gene and poor outcome in HCC has been not been performed. We therefore investigated the correlation of MACC1 single nucleotide polymorphisms (SNPs) with tumor recurrence and overall survival in HCC patients undergoing liver transplantation (LT). Methods: The study included 187 HCC patients treated with LT. Five polymorphisms in the MACC1 gene (rs1990172, rs3735615, rs4721888, rs2241056, rs975263) were genotyped in 183 cases of tumorous tissue sample and 117 cases of adjacent normal tissue sample using SNaP-Shot assays. The association of SNPs with tumor recurrence and overall survival was then analyzed by additive, dominant, recessive, and overdominant models in a cohort of 156 HCC patients. Results: In terms of tumor recurrence, heterozygous of SNP rs1990172 and SNP rs975263 showed a significant high risk of relapse using univariate and multivariate analysis (overdominant, HR(95%CI)=2.27 [1.41-3.66], P=0.001; HR(95%CI)=2.16 [1.37-3.39], P=0.001). But the difference between heterozygous of these two SNPs and overall survival did not reach a significance in all models. The other three investigated SNPs were not significantly associated with tumor recurrence and overall survival (P>0.05). In addition, we found no significant difference in genotype frequencies between HCC and controls. Conclusions: Our data suggest that SNP rs1990172 and SNP rs975263 in the MACC1 gene may be potential genetic markers for HCC recurrence in LT patients.

Factors associated with potentially inappropriate medications use by the elderly according to Beers criteria 2003 and 2012

Potentially inappropriate medications (PIMs) should be avoided by the elderly because they possess a significant high risk for this population when a safer alternative is available. Therefore, the identification of prevalence and factors associated with PIMs should be considered as they provide valuable information that can be used to develop strategies to ensure patients' safety. To identify the prevalence and the clinical and socioeconomic-demographic factors that may be associated with PIMs use in the elderly, according to Beers criteria 2003 and its updated version 2012. And, as a secondary objective, a comparison between both criteria was performed. Pharmacy of the Basic Health District Unit of the western district of Ribeirão Preto. This cross-sectional observational study was conducted with the elderly, assisted by the Brazilian public health system. Data from patients were collected through a structured interview form. Beers criteria 2003 and 2012 were used to classify PIMs. The association between PIMs used and independent variables were analyzed by odds ratios. The differences between PIMs use according to Beers criteria 2003 and 2012 were analyzed by McNemar's test and the agreement by kappa coefficient. Prevalence and factors associated with PIMs use in Brazilian elderly outpatients. One thousand elderly patients were interviewed. High prevalence of PIMs use was observed, 48.0 and 59.2 % according to Beers criteria 2003 and 2012, respectively. The factors associated with PIMs use, common for both criteria, are female gender, self-medication, use of over the counter drugs, complaints related to adverse drug event, psychotropic medication, polypharmacy and some categories of drugs. PIMs use is different between Beers criteria 2003 and 2012 (McNemar's test, p < 0.01), although a substantial agreement between these classifications was observed (kappa coefficient 0.635, 95% confidence intervals (0.588, 0.681). Our study showed a high prevalence of PIMs use, which is associated with various clinical and social-demographic factors. When comparing both criteria through McNemar's test, PIMs use was considered different. The differences may have occurred because medications with high prevalence of use in Brazil were included in Beers criteria 2012 .

Abstract B49: Prediagnostic body-mass index, smoking, and prostate cancer survival

Abstract Background: Few prospective studies have sufficient power to investigate the relationship between obesity and lethal prostate cancer (PC) in detail or within population subgroups, such as by smoking status. This study aimed to investigate the associations of pre-diagnostic body mass index (BMI) with risk of progression from time of PC diagnosis to fatal outcome, to assess effect modification by smoking status and to evaluate the joint effect of BMI and smoking on PC survival. Methods: We conducted a survival analysis of 10,206 PC patients from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). BMI and smoking status were estimated before PC diagnosis. Deaths among PC patients were categorized into deaths from PC and other causes. We conducted the analysis in 3 parts according to exposures: BMI (18-22.9 kg/m2, 23-24.9 kg/m2. 25-27.9 kg/m2, 28-29.9 kg/m2, 30-34.9 kg/m2, 35 kg/m2+), smoking (Never, former, current) and their joint effect, respectively. Each analysis was performed on prostate cancer specific mortality and other mortality separately. Competing-risks regression model was used to take into account of other causes of death. For the above analyses, two models were used. Model 1 controlled for age at diagnosis, drinking status, diabetes status, cohort, duration between baseline and PC diagnosis; Model 2 further adjusted for PC stage and Gleason score at diagnosis in addition to model 1. Results: There were 1028 deaths from PC and 1919 other deaths among all PC patients during an average follow up of eight years. Higher BMI was associated with higher risk of death from PC and other causes; compared to BMI (23-24.9 kg/m2) group, men with BMI 35+ kg/m2 had HR=1.83, 1.16-2.91 for PC death and HR=1.49, 1.04-2.14 for other deaths. The positive trend was apparent only among never and former smokers but not current smokers. Similar effect was found among men whose BMI measured &amp;gt;5 years but for men whose BMI was measured &amp;lt;=5 years before PC diagnosis, only those in the highest category (BMI 35+ kg/m2) was associated with higher risk of dying from PC. Former smokers as well as current smokers have significant higher risk of progressing to death after PC diagnosis regardless BMI with significant interaction between BMI and smoking. Conclusions: Higher BMI and smoking history (former and current smokers) are possible risk factors for dying from PC among all PC cases in the BPC3 cohort. The effect of BMI on PC survival is modified by smoking status. Citation Format: Changzheng Yuan, Jorge Chavarro, Sara Lindström, Peter Kraft, Jing Ma. Prediagnostic body-mass index, smoking, and prostate cancer survival. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B49.

Cardiac Morbidity of Carotid Endarterectomy Using Regional Anesthesia Is Similar to Carotid Stent Angioplasty

Carotid artery stenting (CAS) was presented by carotid revascularization endarterectomy versus stenting trial as a minimally invasive approach with less risk of postoperative myocardial infarction (MI) when compared to carotid endarterectomy (CEA). Our study aimed to compare the postoperative MI rate for CAS with CEA under general anesthesia (GA) and local anesthesia (LA). A retrospective study was conducted at our institution comparing CAS with CEA under LA and CEA under GA. Thirty-day postoperative MI and strokes were evaluated for the different subgroups. A total of 1127 procedures were included in the analysis: 421 CEAs under GA, 611 CEAs under LA, and 95 CAS. No significant difference in postoperative MI was encountered between CAS and CEA under LA (0.2% vs 1.1%, P = .25). The CEA under GA was found to have a statistically significant higher risk of MI compared to LA (1.2% vs 0.2%, P = .044). Our evidence suggests that CEA under LA does not have an increased risk of MI compared to CAS.