Investigating the Efficacy of EGFR-TKIs and Anti-VEGFR Combination in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis.

INTRODUCTION: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based on generations remains to be explored. This study estimated the survival outcomes of EGFR-TKIs plus anti-VEGFR in combination in defined populations of advanced non-small cell lung cancer (NSCLC) patients overall, as a first- or second line of treatment, with different generations of EGFR-TKIs and EGFR-TKIs plus bevacizumab combination as a subgroup. METHODS: A literature search was conducted using PubMed, SCOPUS, Cochrane Library, and ClinicalTrials.gov databases through June 2023 to identify primary research reporting the survival outcomes of EGFR-TKIs in combination with anti-VEGFR agents in patients with advanced NSCLC. Studies that were single-arm, published in non-English languages, and had missing data on survival outcomes were excluded. A meta-analysis was conducted to generate pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Methodological quality and risk of bias in studies were assessed using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool. RESULTS: A total of 20 randomized controlled trials were included in the qualitative synthesis, and 11 (2182 participants) were included in the meta-analysis. Patients' median age ranged from 58 to 68 years; 36% to 70% of patients were female; most of them had IIIa/b to IV stage cancer. In meta-analyses, the EGFR-TKIs plus anti-VEGFR combination resulted in improved PFS (HR, 0.73; 95% CI: 0.61, 0.86; p < 0.00001) in patients with advanced NSCLC but had no impact on OS (HR, 0.93; 95% CI: 0.79, 1.10; p = 0.41). The first line of treatment and first-generation EGFR-TKIs with the combination also improved the PFS (HR, 0.64; 95% CI: 0.57, 0.71; p < 0.00001; HR, 0.63; 95% CI: 0.56, 0.71; p < 0.00001) respectively, however, had no impact on OS. CONCLUSIONS: Our meta-analysis indicated EGFR-TKIs with anti-VEGFR in combination not only improved overall PFS but also showed similar results to a first line and first-generation agent compared to EGFR-TKI alone.

Genetic variations in a Sestrin2/Sestrin3/mTOR Axis and development of new-onset diabetes after kidney transplantation.

BACKGROUND: Genetic variations in Sestrin2/Sestrin3/ mTOR axis may cause obesity-associated metabolic syndrome, including lipid accumulation and insulin resistance thereby increasing individual's risk of diabetes. In this study, we explored the association between single nucleotide polymorphisms (SNPs) of these genes and new onset diabetes after transplantation in Hispanic renal transplant recipients (RTRs). METHODS: Nine potential functional polymorphisms in Sestrin2, Sestrin3 and mTOR genes were genotyped using the Taqman qPCR method in this study. We compared 160 Hispanic RTRs with no evidence of pre-existing diabetes, who developed new onset diabetes after transplantation (NODAT) with 152 controls with no history of diabetes. The logistic proportional hazard model was used to examine risks for NODAT. Nongenetic and genetic characteristics were included in the multivariate risk model. RESULTS: Significant associations were observed between NODAT and mTOR TT (rs2295080 OR = 1.79, 95% CI =1.14-2.82, p = 0.01), Sestrin2 AA (rs580800, OR = 0.42, 95% CI =0.27-0.67, p = 0.002), and Sestrin3 AA (rs684856, OR = 0.45, 95% CI = 0.27-0.75, p = 0.001). Sestrin2 AA (rs580800), Sestrin3 AA (rs684856) and mTOR TT (rs2295080) remained significantly associated with NODAT after adjusting for acute rejection and sirolimus use. No interactions observed between the mTOR rs2295080 and Sestrin3 rs684856 and risk of NODAT (mTOR rs2295080 and Sestrin3 rs684856, p = 0.123 and mTOR rs2295080 and Sestrin2 rs580800, p = 0.167). Of the nongenetic factors, use of sirolimus and older age were associated with an increased risk for NODAT. CONCLUSION: Polymorphisms in the Sestrin2/Sestrin3/ mTOR gene may confer certain protection/predisposition for NODAT.

Comparing Efficacy of Erlotinib and Bevacizumab Combination with Erlotinib Monotherapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors searched databases such as PubMed, Medline, Scopus, and Cochrane Central Register of Controlled Trials for randomized control trials (RCTs) comparing erlotinib plus bevacizumab with erlotinib in NSCLC patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were the outcomes of interest. The pooled hazard ratio (HR) and relative risk (RR) were estimated utilizing both fixed- and random-effect models. Methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool. Nine studies comprising 1698 patients with NSCLC were included in this meta-analysis, of whom 850 were treated with erlotinib plus bevacizumab, and 848 with erlotinib. The erlotinib plus bevacizumab combination significantly prolonged PFS (HR, 0.62, 95% CI: 0.56, 0.70, p < 0.00001) but did not show any significant improvement in OS (HR, 0.95; 95% CI: 0.83, 1.07, p = 0.39) and ORR (HR, 1.10; 95% CI: 0.98, 1.24, p = 0.09). Increased risks of hypertension (RR, 5.15; 95% CI: 3.59, 7.39; p < 0.00001), proteinuria (RR, 10.54; 95% CI: 3.80, 29.20; p < 0.00001) and grade 3 and higher AEs (RR, 2.09; 95% CI: 1.47, 2.97; p < 0.00001) were observed with the erlotinib-plus-bevacizumab combination compared to erlotinib monotherapy. On subgroup analyses, the erlotinib plus bevacizumab combination improved PFS only. Combining erlotinib and bevacizumab has been shown to improve PFS in advanced NSCLC patients but did not show any significant OS and ORR benefits. Furthermore, risks of hypertension, proteinuria, and grade 3 or higher AEs were greater with the erlotinib-and-bevacizumab combination.

Application of Exploratory Factor Analysis and Item Response Theory to Validate NHANES ADL Scale in Patients Reporting Rheumatoid Arthritis.

Background: Several instruments are used for measuring functional limitations among rheumatoid arthritis (RA) patients. However, these instruments are incongruously assessed for their psychometric properties. The National Health and Nutritional Examination Survey (NHANES) uses a generic questionnaire to assess the activities of daily living (ADL) to measure functional limitations among its participants. The psychometric properties of the NHANES-ADL scale were evaluated using a patient examination and survey data. Methods: NHANES-ADL scale was assessed for its internal consistency and factor structure. Scale reliability was assessed with Cronbach's alpha reliability coefficient. Principal component analysis with Promax rotation was used to obtain factor structure. Confirmatory factory analysis was used to calculate fit indices. The graded item response theory model was used to estimate item discrimination, difficulty, and test information. Results: Our sample included 1132 individuals with RA. Exploratory factor analyses of 19-item NHANES ADL scale produced one factor solution and accounted for 35% of variance. The Cronbach alpha of this scale was 0.92. The results of graded item response model indicated items performing well discriminating high and low level of functional ability. A higher slope (α) reflected stronger ability of items to discriminate across the continuum. Conclusions: The NHANES ADL scale showed good reliability, single dimensionality, and validity in RA patients. Studies should explore its test-retest reliability and its ability to reliably measure functional change over time in the future.

Examining Health Disparities and Severity of Depression among Sexual Minorites in a National Population Sample.

Background: Health disparities and mental health issues have not been fully explored among sexual minorities. This study aims to examine health disparities and severity of depression among sexual minorities using a nationally representative sample of the US population. Methods: The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2016 were analyzed. The Patient Health Questionnaire (PHQ-9) was used to examine the severity of depression among sexual minorities compared to heterosexuals. Data were analyzed for descriptive statistics and associations using the Chi-squared test. A multivariate logistic regression analysis was used to quantify the magnitude of association between severity of depression and demographic characteristics. A p-value of <0.05 was considered statistically significant. Results: Among 7826 participants included, 426 (5.4%) were identified as a sexual minority. Moderately severe to severe depression was observed among 9.3% of sexual minorities with women having higher rates (64.2%) than men. Similarly, sexual minorities were two times more likely to have moderately severe to severe depression, two and half times more likely to see a mental health professional, and one and half times more likely to have genital herpes and be a user of illicit drugs than heterosexuals. In addition, they were less likely to be married and more likely to have been born in the United States, be a U.S. citizen, and earn less than USD 25,000 (p < 0.05). Conclusions: Sexual minorities are affected by a range of social, structural, and behavioral issues impacting their health. The screening of individuals with depression who are sexual minorities (especially females), illicit drug users, poor, or aged over 39 years may benefit from early intervention efforts.

Co-Occurring Depression and Associated Healthcare Utilization and Expenditure in Individuals with Respiratory Condition: A Population-Based Study.

The existing literature is limited on the prevalence of depression among people with respiratory conditions and person-level factors that are associated with increased healthcare utilization and expenditures. The aim of this study was to explore the prevalence, pattern of healthcare use, and expenditures in noninstitutionalized individuals having co-occurring depression with respiratory conditions. The Medical Expenditure Panel Survey (MEPS) data from 2011 to 2017 was used in this study. Our sample included individuals having respiratory conditions (asthma, emphysema, and chronic bronchitis) with and without depression. Healthcare use and expenditure data were analyzed using a chi-square test, t-tests, and multiple linear regression analyses. There were 8848 individuals in the study. The prevalence of comorbid depression was 20%. Individuals with co-occurring depression with respiratory conditions differed significantly from individuals without co-occurring depression for age ≥ 45 years, white, and with ≤2 chronic disease conditions. Depressed individuals with respiratory conditions had higher healthcare utilization and expenditures. The presence of co-occurring depression with respiratory conditions increases the treatment complexity, healthcare utilization, and expenditure. Better treatment and management of these patients may reduce healthcare use and expenditures in the future.

A Population Based Study of Liver Function amongst Adults with Hyperuricemia and Gout in the United States.

To examine the association between uric acid levels and liver enzyme functions amongst adults with hyperuricemia and gout in the United States. The National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016 was used to study the research objective. Data were analyzed for descriptive statistics and for differences using the t test, Chi-square test and ANOVA. A regression analysis was performed to determine association between demographics and liver enzymes. A p value of <0.05 or <0.001 was considered statistically significant. A total of 14,946 adults (≥20 yrs.) were included in this study. Sample mean age was 49 ± 0.15 yrs., and 54% were female. Overall, 15% adults had elevated uric acid levels (≥6.8 mg/dL), men had significantly higher uric acid levels than women (6 mg/dL vs. 4.8 mg/dL). High uric acid levels were associated with more than two times higher odds of elevated ALT, AST and GGT (p < 0.001). Similarly, gender-based target uric acid values were associated with two-fold increased odds of GGT, over one-and-a-half fold higher odds of ALT and AST (p < 0.001). Regression analysis showed significant association between age, gender, race/ethnicity, body mass index, and hypertension and ALT, AST, ALP, total bilirubin and GGT (p < 0.001). Adults with hyperuricemia and gout are most likely to develop liver dysfunctions and suffer associated morbidities. Such patients need to be appropriately monitored and managed for their liver functions and to prevent associated morbidities.

Examining Liver Function in Adults with Diabetes in the United States.

PURPOSE: Hyperglycemia is the hallmark of various types of diabetes and considered to be a risk factor for several chronic disorders including liver function. Though liver is a dynamic organ, incessant glucotoxicity can lead to altered liver function. The goals of the present study were to examine the association between diabetes with liver functions amongst adults in the United States. METHODS: We analyzed 14,948 adults with diabetes in the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2016. Diabetes and prediabetes were defined in accordance with the American Diabetes Association 2021 guidelines. The association of demographic characteristics with glycemic levels was analyzed using the Chi-square test. A multivariate logistic regression model was constructed to evaluate the associations of glycemic levels with abnormal liver enzyme levels. Regression model was adjusted for age, sex, and ethnicity. The statistical analyses were performed using STATA ver. 14. A. p value of ≤0.05 or≤0.001 was considered statistically significant. RESULTS: A total of 14,948 adults (20 years and above) were included in this study. Sample mean age was 45.5±0.33 yrs., 54% were female, 53% were non-Hispanic White, and 60% had some college or graduate level education. In the overall sample, 19% adults were diabetic and 34% were pre-diabetic. Pre-diabetic glycemic levels were associated over one and half times higher odds of ALT (OR: 1.45, 95% CI: 1.31, 1.60, p<0.001) and over 1.3 times of higher odds AST (OR: 1.30, 95% CI: 1.14, 1.49,p<0.001). On the other hand, diabetic glycemic levels were associated with close to one and half times higher odds of ALT (OR: 1.37, 95% CI: 1.18, 1.59,p<0.001) and AST (OR: 1.48, 95% CI: 1.24, 1.76, p<0.001). On regression analysis, after adjustment, pre-diabetic and diabetic status was associated with high ALT (OR: 1.21, 95%CI: 1.11, 1.32, p<0.001), AST (OR: 1.14, 95%CI: 1.04, 1.27, p<0.05), ALP (OR: 1.40, 95%CI: 1.16, 1.68, p<0.001) and GGT (OR: 1.42, 95%CI: 1.24, 1.63, p<0.001). CONCLUSIONS: Our results indicated that diabetes is significantly associated with liver function. This observed association deserves further exploration to understand the longitudinal impact of diabetes on liver function.

Association Between Polymorphisms in Cytokine Gene and Viral Infections in Renal and Liver Transplant Recipients: A Systematic Review.

PURPOSE: Although transplantations are associated with an increased risk of post-transplantation infections, they greatly improve life expectancy and patients' quality of life. Cytokine genes play an important role in the success of transplants due to their immunological functions. A systematic review was conducted to evaluate cytokine gene polymorphisms and risk of cytomegalovirus (CMV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in kidney and liver transplant recipients. METHODS: A systematic search was conducted using PubMed, EMBASE, Medline and Google Scholar from their inception until January 28, 2019 using appropriate key words. Review articles, case reports or series, studies conducted on non-human subjects and published in languages other than English were excluded. Data were abstracted using a standardized form. The quality of the studies included was assessed using "Risk of Bias Assessment tool for Non-randomized Studies (RoBANS)". RESULTS: Thirty-one studies met our inclusion criteria; populations studied were diverse with a sample ranging from 20 to 1,671. Nineteen studies evaluated Interleukin (IL)-28B polymorphism, while six studies evaluated interferon lambda (IFN-λ) gene polymorphisms and their impact on CMV, HCV, and HBV progression. Polymorphisms in IL-10 gene were investigated in six studies. Polymorphisms in IL-12B and IL-1B gene were associated with a higher risk of developing CMV infections while polymorphisms in IL-28B were associated with a lower incidence of CMV infection in renal transplant recipients. Similarly, polymorphisms in IL-28B were associated with higher liver dysfunction from HBV infection in liver transplant recipients. Studies included had low risk of bias. CONCLUSIONS: Cytokine gene polymorphisms IL-12B and IL-1B were found to be associated with an increased risk of infection in kidney transplants and IL-28B in liver transplant recipients. However, the small number and heterogeneity of studies limits the generalization of our results. Further research may lead to finding these associations in larger studies which perhaps improve the use of genetic testing and targeted antiviral therapy. This will further reduce the risk of viral infections associated with cytokine gene polymorphisms in post renal and liver transplant recipients.

A Population-Based Cross-Sectional Study of the Association between Liver Enzymes and Lipid Levels.

BACKGROUND: To examine the association between low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels and liver enzyme functions. METHODS: The National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2012 was used to examine the association between liver enzymes and lipid levels amongst adults in the United States. RESULTS: Sixteen percent adults had ALT > 40 U/L, 11% had AST > 40 U/L, and 96% had ALP > 120 U/L. Age, gender, and race/ethnicity showed significant association with LDL, HDL, and triglycerides levels. LDL greater than borderline high was associated with little over two times higher odds of elevated ALT (OR: 2.33, 95% CI: 2.17, 2.53, p ≤ 0.001) and AST (OR: 2.79, 95% CI: 2.55, 3.06, p ≤ 0.001). High HDL was associated with 50% higher odds for elevated ALT (OR: 1.51, 95% CI: 1.39, 1.64, p ≤ 0.001) and over two-and-half fold elevated AST (OR: 2.77, 95% CI: 2.47, 3.11, p ≤ 0.001). LDL-C, HDL-C, and triglycerides were found to be good predictor of elevated ALT, AST, and ALP levels. Similarly, old age and female gender were significant predictor of elevated ALT and AST (p ≤ 0.001). CONCLUSIONS: Underlying hepatic pathophysiology from dyslipidemia deserves further exploration due to its potential effects on hepatic drug metabolism/detoxification.

Lead Poisoning Due to Herbal Medications.

Many herbal products are harmless or possess minimal toxicity, whereas, some contain toxic ingredients that may not be identified due to lack of quality control or not listed on the label. Over the years, several case reports and studies have documented that herbal medications may contain ingredients that are toxic. Several studies have documented that some herbal medications contained high concentrations of heavy metals, such as lead, mercury, and arsenic. Publications of such case reports and studies have repeatedly reminded us that we have failed in our legal and civic duties of educating users of herbal medications and general population about the grave concerns posed by the herbal medications and their associated toxicities.

Antibacterial, antioxidant and cell proliferative properties of Coccinia grandis fruits.

OBJECTIVE: Little knowledge is available on the antimicrobial and antioxidant properties of Coccina grandis fruits and no study has reported on its cell proliferative property. The aim of this study was to examine the antimicrobial, antioxidant and cell proliferative property of fruits of C. grandis. MATERIALS AND METHODS: Fruits of C. grandis were extracted using water; ethanol and acetone by cold and hot Soxhlet extraction. The antibacterial activities of the extracts were tested against Staphylococcusaureus,Enterococcusfaecalis,Escherichiacoli and Pseudomonasaeruginosa using the modified Kirby-Bauer diffusion method and compared against erythromycin. The antioxidant property was determined using Cayman's antioxidant assay; whereas cell proliferation/cytotoxic properties were evaluated using the Cell Titer 96 Aqueous One Solution Cell MTS assay with MDA-MB 321 breast cancer cells. Data were analyzed for correlation and differences using unpaired student's t-test and one-way ANOVA. A p value of <0.05 was considered statistically significant. RESULTS: Both cold and hot ethanol and acetone extracts of C. grandis fruits showed some degree of bacterial growth inhibition. Acetone extracts exhibited higher antibacterial activity. Both ethanol extracts showed antioxidant property when compared with standard Trolox. In contrary to cytotoxicity, all four extracts showed cell proliferation compared to controls at different concentrations. However, acetone extracts exhibited greater cell proliferation compared to ethanol extracts and cold extracts performed better than the hot extracts. CONCLUSION: C. grandis fruits exhibited some degree of antimicrobial, antioxidant and cell proliferative properties. Further investigation is warranted to isolate, confirm and characterize phytochemicals that are responsible for the medicinal properties observed.

A Team-based Assignment to Integrate Basic Science and Pharmacotherapeutic Principles for Anticancer Agents.

Objective. To implement and evaluate an active-learning, team-based assignment centered on anticancer agents for the integration of basic science and pharmacotherapeutic principles. Methods. Student teams were assigned a specific anticancer agent and were expected to answer a series of questions on the written section of the assignment, followed by a presentation to the class. Each assignment was assessed using a grading rubric that was mapped to the 2013 CAPE educational outcomes. Student perceptions of the assignment were assessed using a short survey. Results. Student cohort performance on the assignment was in the B range (83%) with a mean of 33.2 out of 40. Using the grading rubric, the 12 student cohorts performed particularly well under professionalism (Domain 4.4) that focuses on personal and professional development from CAPE 2013 with means >4 on a 1-5 scale. Student impressions of the assignment suggested that students believed the assignment had a positive effect on their learning and should be continued. Conclusion. The assignment provided a focused review of basic science and pharmacotherapeutic principles and enabled integration of concepts relating to the therapeutic application of anticancer agents, and management of anticancer agent mediated adverse effects. The assignment could contribute toward preparing students for the evolving role of the pharmacist in the management of cancer.

Development and validation of PSPSQ 2.0 measuring patient satisfaction with pharmacist services.

BACKGROUND: The extant literature reveals a lack of psychometrically validated tools measuring patient satisfaction with pharmacist clinical services. The Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ 2.0) was developed to address this need using a mixed methods approach. OBJECTIVE: To assess the psychometric properties of the PSPSQ 2.0, an instrument developed to measure patient satisfaction with clinical services provided by pharmacists. METHODS: Validation studies were conducted in two Veterans Affairs (VA)-based and two community-based (diabetes and psychiatric care) disease management/medication therapy management clinics. The PSPSQ 2.0 consisted of 22-items related to three domains identified as quality of care, patient-pharmacist relationship and overall satisfaction using a 4-point, Likert-type scale. It was administered to participants following their session with a pharmacist at the clinics. Collected data were analyzed for descriptive statistics, internal consistency, and validity using exploratory factor analysis. RESULTS: A total of 149 patients completed the survey. Patients from VA clinics were on average 61 years old, mostly white (63%), and predominantly male (95%). Patients from non-VA clinics were on average 47 years old, mostly White (47%) and male (53%). Non-VA patients mostly had Medicaid (42%) and commercial health insurance (31%), whereas VA patients retained benefits with the US Department of Veterans Affairs. Reliability of the scale using internal consistency metrics revealed a Cronbach's alpha of 0.98, 0.98 and 0.95 for VA, diabetes, and psychiatric care clinics, respectively, whereas the Cronbach's alpha for the pooled sample was 0.96. Factor analyses resulted in a three-factor solution accounting for 91% and 69% variance for diabetes and psychiatric care clinics, respectively; however, VA clinics and pooled sample yielded only 2-factor solution with 80% and 66% variance, respectively, with more items loading on patient-pharmacist relationship domain. CONCLUSIONS: The results suggest that the PSPSQ 2.0 can serve as a reliable and valid tool for measuring patient satisfaction with pharmacists providing clinical services in VA- and non-VA settings upon further validation.

Taking stock of medication wastage: Unused medications in US households.

BACKGROUND: Despite the potential deleterious impact on patient safety, environmental safety and health care expenditures, the extent of unused prescription medications in US households and reasons for nonuse remain unknown. OBJECTIVE: To estimate the extent, type and cost of unused medications and the reasons for their nonuse among US households. METHODS: A cross-sectional, observational two-phased study was conducted using a convenience sample in Southern California. A web-based survey (Phase I, n = 238) at one health sciences institution and paper-based survey (Phase II, n = 68) at planned drug take-back events at three community pharmacies were conducted. The extent, type, and cost of unused medications and the reasons for their nonuse were collected. RESULTS: Approximately 2 of 3 prescription medications were reported unused; disease/condition improved (42.4%), forgetfulness (5.8%) and side effects (6.5%) were reasons cited for their nonuse. "Throwing medications in the trash" was found being the common method of disposal (63%). In phase I, pain medications (23.3%) and antibiotics (18%) were most commonly reported as unused, whereas in Phase II, 17% of medications for chronic conditions (hypertension, diabetes, cholesterol, heart disease) and 8.3% for mental health problems were commonly reported as unused. Phase II participants indicated pharmacy as a preferred location for drug disposal. The total estimated cost for unused medications was approximately $59,264.20 (average retail Rx price) to $152,014.89 (AWP) from both phases, borne largely by private health insurance. When extrapolated to a national level, it was approximately $2.4B for elderly taking five prescription medications to $5.4B for the 52% of US adults who take one prescription medication daily. CONCLUSION: Two out of three dispensed medications were unused, with national projected costs ranging from $2.4B to $5.4B. This wastage raises concerns about adherence, cost and safety; additionally, it points to the need for public awareness and policy to reduce wastage. Pharmacists can play an important role by educating patients both on appropriate medication use and disposal.

Association of interferon gamma gene polymorphisms with BK virus infection among Hispanic renal allograft recipients.

BACKGROUND: BK virus nephropathy is one of the most common viral infections that affect up to 10% of renal transplant recipients (RTRs), causing allograft dysfunction and graft loss. Interferon-gamma (IFN-γ) gene polymorphisms have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection, cytomegalovirus viremia, and disease. IFN-γ is known to have potent inhibitory effects on BK virus gene expression, both at the level of transcription and translation. METHODS: It was investigated whether IFN-γ polymorphisms are associated with BKV infection. Genotyping of four single-nucleotide polymorphisms located in the IFN-γ gene were performed on DNA collected from a total of 251 RTRs (71 RTRs with BKV infection and 180 without BKV infection). RESULTS: Analysis of the results showed that IFN-γ (rs12369470) CC genotype was significantly associated with susceptibility to BKV infection (OR: 2.9, 95% CI: 1.29-6.44, P=0.007) while the IFN-γ +874 (rs2435061) TT and (rs2406918) CC genotypes appear to be markers for protection against BKV infection (OR: 0.29, 95% CI: 0.1-0.83, P=0.01 for rs245061; OR: 0.61, 95% CI: 0.4-0.94, P=0.02 for rs24069718). A haplotype analysis using the combination of rs2435061-rs2406918-rs2870953 showed that the A-G-T haplotype was associated with a significantly reduced risk for BKV infection (OR: 0.43, 95% CI: 0.25-0.73, P=0.001). CONCLUSION: Polymorphisms in the IFN-γ gene may confer certain protection or predisposition for BKV infection.

Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients.

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.

Impact of NF-κB gene polymorphism on allograft outcome in Hispanic renal transplant recipients.

BACKGROUND: The dimeric NF-κB transcription factors play critical roles in diverse cellular processes including adaptive and innate immunity, cell differentiation, proliferation and apoptosis. It regulates the expression of numerous genes that play a key role in the inflammatory response during kidney allograft rejection. This study aims to determine the association of NF-κB gene polymorphisms with allograft outcomes in the Hispanic renal transplant recipients. METHODS: A total of 607 Hispanic renal transplant recipients at St. Vincent Medical Center between 2001 and 2010 were included in this study. The NF-κB genotypes were studied along with clinical data. In the case of NF-κB genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF-κB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-κB2 (rs1056890, rs7897947, rs12769316) and NF-κB inducing kinase (NIK) (rs9908330, rs7222094). The association of each genotype with renal allograft survival and acute rejection was evaluated. RESULTS: NF-κB1 (rs3774937) CC genotype showed protective association with allograft rejection (OR=0.66, 95% CI=0.44-0.99, p=0.04). There was a significant increase in allograft survival time associated with the NF-κB1 (rs3774959) A allele (OR=0.76, 95% CI=0.60-0.98, p=0.03) while GG genotype was associated with a higher risk of graft failure (OR=1.51, 95% CI=1.02-2.21, p=0.03). There were no associations between polymorphic markers in NF-κB2 and NIK genes with allograft survival or acute rejection. Among non-genetic factors, we found that the use of tacrolimus, a deceased donor, delayed graft function and acute rejection were associated with allograft failure. CONCLUSION: The result of present study suggests that NF-κB1 gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.