TP53 gene mutations of lung cancer patients in upper northern Thailand and environmental risk factors

Abstract TP53 mutations are observed in about 40e70% of lung cancer tissues, and the hot spot codon mutations are in exons 5 through 8. Previous studies revealed that the distinct TP53 mutational pattern between population groups may be due to different racial or exogenous factors. This research aims to identify risk factors that influence TP53 gene mutation in lung cancer patients residing areas with high lung cancer incidence, in the upper northern part of Thailand. Germline TP53 mutational analyses were also performed to determine the inherited cancer predisposition. Exons 5e8 of the TP53 gene were analyzed by sequencing DNA of cancerous tissue and peripheral blood leukocyte samples from 55 nonesmall lung cell cancer patients. The results showed that the TP53 germline mutation was not found in all patients, indicating that the TP53 germline mutations were not exclusively responsible for cancer predisposition in this group of lung cancer patients. A total of 19 somatic mutations were found in 18 patients. Mutations were predominantly found in exons, with only 10.53% observed at the splice sites of intron 7. No characteristic hot spot codons were observed. The data suggest that TP53 mutations in this study group are induced by exposure to substances other than tobacco smoke. Pesticide exposure or habitation in poorly ventilated houses may instead be related to the tumorigenesis of lung cancer via TP53 mutations.

Haematological Safety of Perinatal Zidovudine in Pregnant HIV-1–Infected Women in Thailand: Secondary Analysis of a Randomized Trial

OBJECTIVES: To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1−infected pregnant women. DESIGN: Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis. SETTING: 27 hospitals in Thailand. PARTICIPANTS: 1,436 HIV-infected pregnant women in PHPT-1. INTERVENTION: Zidovudine prophylaxis initiation at 28 or 35 wk gestation. OUTCOME MEASURES: Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load. RESULTS: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] −0.4 [−0.5 to −0.3], −423 [−703 to −142], −485 [−757 to −213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts. CONCLUSION: Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV

Impact of antiretroviral treatment on height evolution of HIV infected children

International audienceBackground: Antiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART.Methods: To describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events.Results: A total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < − 2), 49% presented stunting (height-for-age z-score < − 2), and 7% wasting (weight-for-height z-score < − 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height.Conclusions: he younger the children at ART initiation, the greater the effect on height-growth velocity,supporting the World Health Organization’s recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation

Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients

<p>Abstract</p> <p>Background</p> <p>Radiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients.</p> <p>Methods</p> <p>Patients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication.</p> <p>Results</p> <p>A total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001).</p> <p>Conclusions</p> <p>Live lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.</p

Relationship between Height-Weight Difference Index and Body-Fat Percentage Estimated by Bioelectrical Impedance Analysis in Thai Adults

Introduction. The height-weight difference index (HWDI) is a new indicator for evaluating obesity status. While body-fat percentage (BF%) is considered to be the most accurate obesity evaluation tool, it is a more expensive method and more difficult to measure than the others. Objective. Our objectives were to find the relationship between HWDI and BF% and to find a BF% prediction model from HWDI in relation to age and gender. Method. Bioelectrical impedance analysis was used to measure BF% in 2,771 healthy adult Thais. HWDI was calculated as the difference between height and weight. Pearson’s correlation coefficient was used to assess the relationship between HWDI and BF%. Multiple linear and nonlinear regression analysis were used to construct the BF% prediction model. Results. HWDI and BF% were found to be inverse which related to a tendency toward a linear relationship. Results of a multivariate linear regression analysis, which included HWDI and age as variables in the model, predicted BF% to be 34.508 − 0.159 (HWDI) + 0.161 (age) for men and 53.35 − 0.265 (HWDI) + 0.132 (age) for women. Conclusions. The prediction model provides an easy-to-use obesity evaluation tool that should help awareness of underweight and obesity conditions

Prediction of survival and analysis of prognostic factors for hepatocellular carcinoma: a 20-year of imaging diagnosis in Upper Northern Thailand

Abstract Background To evaluate survival rates of hepatocellular carcinoma (HCC), the Chiang Mai Cancer Registry provided characteristics data of 6276 HCC patients diagnosed between 1998-2020 based on evolution of imaging diagnosis. Evolution can be separated into four cohorts, namely, cohort 1 (1990-2005) when we had ultrasound (US) and single-phase computed tomography (CT), cohort 2 (2006-2009) when one multi-phase CT and one magnetic resonance imaging (MRI) were added, cohort 3 (2010-2015) when MRI with LI-RADS was added, and finally, cohort 4 (2016-2020) when two upgraded MRIs with LI-RADS were added. Methods Cox proportional hazard models were used to determine the relation between death and risk factors including methods of imagining diagnosis, gender, age of diagnosis, tumor stages, history of smoking and alcohol-use, while Kaplan-Meier curves were used to calculate survival rates. Results The median age of diagnosis was 57.0 years (IQR: 50.0-65.0) and the median survival time was 5.8 months (IQR: 1.9-26.8) during the follow-up period. In the univariable analysis, all factors were all associated with a higher risk of death in HCC patients except age of diagnosis. In a multivariable analysis, elderly age at diagnosis, regional and metastatic stages and advanced methods of imagining diagnosis during cohorts 2 and 3 were independently associated with the risk of death in HCC patients. The survival rate of patients diagnosed during cohort 4 was significantly higher than the other cohorts. Conclusion As a significantly increasing survival rate of HCC patients in cohort 4, advanced methods of diagnostic imaging can be a part of the recommendation to diagnose HCC

Association of low CD4 cells count and intra-uterine growth retardation in Thailand

Objective: Each year, intrauterine growth retardation (IUGR) affects 20-30 million neonates worldwide, mostly in resource-limited settings. Increased perinatal and infant mortality has been associated with IUGR. Some studies have suggested that HIV infection could increase the risk of IUGR. To confirm this hypothesis, we examined the association between HIV-related factors and the risk of IUGR in Thailand. Patients and Methods: Data from a cohort of 1436 HIV-infected pregnant women enrolled in the “Perinatal HIV Prevention Trial-1”, a clinical trial conducted from 1997 to 1999 in Thailand, were analyzed using a logistic regression, adjusting for risk factors usually associated with IUGR. Results: The rate of IUGR was 7.6%. Adjusting for a short maternal height, low body mass index, small weight gain during pregnancy, and infant female sex, a low maternal CD4 percentage was independently associated with IUGR (odds ratio 0.96, per 1% increment, 95% confidence interval 0.93 to 0.99, P = 0.03). Conclusions: The current World Health Organization recommendation to initiate combination antiretroviral therapy for immunocompromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of IUGR. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of IUGR