Circulating thrombospondin-2 in patients with moderate-to-severe chronic heart failure due to coronary artery disease

Chronic heart failure (CHF) remains a leading cause of morbidity and mortality. In the current study, we aimed to evaluate the predictive value of circulating thrombospondin-2 (TSP-2) for cumulative survival in patients with ischemic CHF due to coronary artery disease (CAD). The results showed that during a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repeatedly. The median circulating levels of TSP-2 in patients who survived and those who died were 0.63 ng/mL (95%CI = 0.55-0.64 ng/mL) and 1.03 ng/mL (95% CI = 0.97-1.07 ng/mL) (P<0.001). Circulating TSP-2 independently predicted all-cause mortality (OR = 1.27; 95%CI = 1.08–1.59; P = 0.002), CHF-related death (OR = 1.16; 95%CI = 1.02–1.50; P<0.001), and also CHF-related rehospitalization (OR = 1.12; 95%CI = 1.07–1.25; P<0.001). In conclusion, among CAD patients with symptomatic CHF, increased circulating TSP-2 is correlated with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization.     

Brucellosis and its associated risk factors to humans and domestic ruminants in Kagera Ecosystem,Tanzania

BackgroundBrucellosis is an important disease for both veterinary and public health. A study was conducted to understand the seroprevalence of brucellosis and its associated risk factors in pastoral areas of Kagera, Tanzania.MethodsSera from 156 patients with malaria-like symptoms were analyzed using the commercial rapid agglutination test (specific for B.abortus and B.melitensis detection) and Fluorescence Polarization Assay (FPA). Sera from 426 cattle, 206 goats and 197 sheep were analyzed using Rose Bengal Plate (RBPT) and Competitive ELISA (c-ELISA) tests.ResultsIn humans, overall brucellosis, B. abortus, and B. melitensis sero-prevalences were 7.7% (95%CI: 3.8–12.2%), 1.9% (95% CI: 0.4–4.5%), and 5.8 % (95%CI: 2.6–10.6%), respectively. At animal level, seropositivity was 5.9% (95%CI: 4.0–8.6%), 2.5% (95%CI: 0.8–5.7%) and 0.5% (95%CI: 0.01–2.8%) in cattle, goats and sheep, respectively. At herd level, seropositivity was 18.2% (95%CI: 12.0–25.8%) in cattle and 6.9% (95%CI: 2.2–15.3%) in small ruminants. Brucellosis was associated with assisting in parturition without wearing protective gears (OR= 5.6; p= 0.02) in humans, herds of 50–200 animals (OR= 4.2, p= 0.01) and cattle (OR=3.5; p=0.01). The knowledge of brucellosis among pastoralists (OR=0.1; p<0.01) was a protective factor.ConclusionBrucella infections could be occurring in pastoralists and domestic ruminants in Kagera. Community health education is necessary for the control of brucellosis in Tanzania.     

What differs former,light and heavy smokers? Evidence from a post-conflict setting

BackgroundEvidence suggests that people who live in regions affected by the armed conflict are more likely to smoke.ObjectiveThe purpose of this study was to assess factors associated with smoking status in a sample of students in the northern Kosovo province.Materials and methodsA total of 514 students enrolled in University in Kosovska Mitrovica, Kosovo, were recruited between April to June 2015 at Student Public Health Center during mandatory health checks. Participants filled in socio-demographic and behavioral questionnaire and Beck Depression Inventory (BDI). Based on responses about smoking, students were categorized in non-smokers, former smokers, light smokers (1–13 cigarettes/day) and heavy smokers (> 13 cigarettes/day).ResultsOf 514 students, 116 (22.6%) classified themselves as smokers. Higher education level of fathers (Odds ratio [OR]=2.89, 95% confidence interval [CI] 1.30–6.44, p=0.009), not living with smokers (OR=0.42, 95%CI 0.15–0.97, p=0.017) and longer exposure to second hand smoke (OR=1.07, 95%CI 1.01–1.13, p=0.036) was associated with former smoking. Studying medical and natural sciences (OR=2.07, 95%CI 1.05–4.18, p=0.040), consuming alcohol (OR=2.98, 95%CI 1.19–10.03, p=0.020), living with smokers (OR=2.88, 95%CI 1.49–5.56, p=0.002), longer exposure to second hand smoke (OR=1.06, 95%CI 1.01–1.11, p=0.019) and having a more intense depressive symptoms (OR=1.08, 95%CI 1.03–1.13, p=0.002) was associated with light smoking. Being male (OR=0.22, 95%CI 0.07–0.41, p=0.001), older (OR=1.47, 95%CI 1.21–1.78, p=0.001), living with smokers (OR=3.78, 95%CI 1.69–8.07, p=0.001), longer daily exposure to second-hand smoke (OR=1.10, 95%CI 1.04–1.16, p=0.001), and having more severe depressive symptoms (OR=1.12, 95%CI 1.07–1.18, p=0.001) were associated with heavy smoking.ConclusionSmoking prevention and cessation programs should include the entire community, because exposure to environmental second hand smoke may facilitate initiation and more intense smoking. Screening of student smokers for depression should be prioritized in the process of rebuilding the framework for primary and secondary prevention in the post-conflict period.     

Systematic review with meta-analysis: Non-alcoholic fatty liver disease and the association with pregnancy outcomes

Background/AimsMaternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD.MethodsWe conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).ResultsTwenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21–16.31; P<0.001; n=7), baseline Hypertension (OR, 3.75; 95% CI, 2.13–6.59; P<0.001; n=4), gestational hypertension (OR, 1.83; 95% CI, 1.03–3.26; P=0.041; n=2), and pre-eclampsia (OR, 2.43; 95% CI, 1.46–4.04; P=0.001; n=3). The odds for a past and current history of gestational diabetes mellitus were OR, 3.78; 95% CI, 2.21–6.44; P<0.001; n=5 and OR, 3.23; 95% CI, 1.97– 5.31; P<0.001; n=6, respectively. As for fetal outcomes, pregnant NAFLD patients were significantly more likely to have a premature birth (OR, 2.02; 95% CI, 1.44–2.85; P<0.001; n=4), large for gestational age birth (OR, 2.01; 95% CI, 1.72–2.37; P<0.001; n=2) or a history of prior miscarriage or abortion (OR, 1.15; 95% CI, 1.02–1.30; P=0.02; n=2). Egger’s regression revealed no evidence of publication bias (P>0.05).ConclusionsThis meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.     

Potential of RASSF1A promoter methylation as a biomarker for colorectal cancer: Meta-analysis and TCGA analysis

The RAS association domain family protein 1A (RASSF1A) is a tumor suppressor in colorectal cancer (CRC), and is often inactived by hypermethylation. Therefore, we evaluated the association between RASSF1A hypermethylation and the risk and prognosis in CRC. We identified literature through searching PubMed and China National Knowledge Infrastructure databases, and then validated and supplemented the meta-analysis with TCGA analysis. Twenty-three studies involving 2886 subjects of CRC were examined. The meta-analysis showed that RASSF1A promoter methylation inferred high CRC risk (odds ratio, 6.53, 95% confidence interval 3.88–11.01, P < .001) and poor overall survival (hazard ratio 2.85, 95% CI 1.88–4.31, P < .001). The TCGA analysis suggested that effect of RASSF1A promotor methylation was affected by tumor localization (colon vs. rectum). RASSF1A promoter methylation was a predictor of high risk (OR 2.38, 95%CI 1.02–5.6, P = .046) and poor disease free survival(HR 2.25, 95%CI 1.27–3.99, P = .006)in colon adenocarcinoma, but the association was statistically insignificant in rectum adenocarcinoma(HR 1.58, 95% CI 0.69–3.59, P = .28). These results suggested RASSF1A hypermethylation is a risk and a potential prognostic biomarker in CRC.     

Seroepidemiology of human fascioliasis and its relationship with anti-Fasciola IgG and liver enzymes as biomarkers of pathogenicity

BackgroundFascioliasis has never been considered a public health concern in Pakistan, although the increasing numbers of human cases reported in south Asia need a re-consideration in the country. The current study aimed to find the seroprevalence of human fascioliasis, associated risk factors and its relationship with liver enzymes as biomarkers of pathogenicity.MethodsThe cross-sectional study was conducted in different districts of Punjab region from May 2014 to August 2016. A total of 546 respondents were screened by using enzyme-linked immunosorbent assay (ELISA) and serum biochemical tests.ResultsHigher seroprevalence was recorded in Muzaffargarh (6.2%) and Bhara kahu (5.9%), while low infection rate in Gujranwala (1.1%) and Islamabad (1.5%). The results of multiple logistic regression analysis showed rural inhabitants (OR=7.9, 95%CI: 2.5–24.8), females (OR=3.5, 95%CI: 1.7–7.1), family size 3–7 (OR=1.7, 95%CI: 1.0–2.9) and socioeconomic condition (OR=3.9, 95%CI: 1.5–10.4) were the significantly (p<0.005) associated risk factors with disease. The results of liver enzymes i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and cholesterol levels were significantly (p=0.001) elevated and associated with fascioliasis pathogenicity.ConclusionThe higher prevalence recorded may explain with Fasciola IgG antibodies for both active and past infections and cross reactivity of the assay with other helminthes.     

Impact of Glycemic Control and Metformin Use on the Recurrence and Progression of Non-Muscle Invasive Bladder Cancer in Patients with Diabetes Mellitus

The purpose of the present study was to determine the potential relationships of glycemic control and use of metformin with non-muscle invasive bladder cancer characteristics. We reviewed data from 645 patients with non-muscle invasive bladder cancer between January 2004 and May 2015. We analyzed the association of pre and post-operative glycemic control and use of metformin with clinical characteristics of bladder tumors. We also analyzed the association of glycemic control and use of metformin with recurrence-free and progression-free survivals. Diabetes mellitus patients showed decreased recurrence-free survival (hazard ratio 1.42; 95% confidence interval 1.1–1.9; P = 0.021) and progression-free survival (hazard ratio 1.79; 95% confidence interval 1.1–2.8; P = 0.013). Diabetes mellitus patients with a HbA1c ≥ 7.0% demonstrated a higher rate of progression (P = 0.026). Kaplan-Meier analysis showed that progression-free survival rate was associated with poor baseline glycemic control (P = 0.026) and post-operative glycemic control (P = 0.025). However, use of metformin had no impact on the recurrence (P = 1.00) and progression (P = 0.282). In conclusion, poor baseline and post-operative glycemic control was related with shorter progression-free survival of patients with non-muscle invasive bladder cancer. Use of metformin had no impact on the recurrence and progression. Therefore, tight glycemic control and close follow-up for bladder tumor may be beneficial in patients with poor glycemic control.     

Non-visible versus visible haematuria and bladder cancer risk: a study of electronic records in primary care

Background

Diagnosis of bladder cancer relies on investigation of symptoms presented to primary care, notably visible haematuria. The importance of non-visible haematuria has never been estimated.

Aim

To estimate the risk of bladder cancer with non-visible haematuria.

Design and setting

A case–control study using UK electronic primary care medical records, including uncoded data to supplement coded records.

Method

A total of 4915 patients (aged ≥40 years) diagnosed with bladder cancer between January 2000 and December 2009 were selected from the Clinical Practice Research Datalink and matched to 21 718 controls for age, sex, and practice. Variables for visible and non-visible haematuria were derived from coded and uncoded data. Analyses used multivariable conditional logistic regression, followed by estimation of positive predictive values (PPVs) for bladder cancer using Bayes’ theorem.

Results

Non-visible haematuria (coded/uncoded data) was independently associated with bladder cancer: odds ratio (OR) 20 (95% confidence interval [CI] =12 to 33). The PPV of non-visible haematuria was 1.6% (95% CI = 1.2 to 2.1) in those aged ≥60 years and 0.8% (95% CI = 0.1 to 5.6) in 40–59-year-olds. The PPV of visible haematuria was 2.8% (95% CI = 2.5 to 3.1) and 1.2% (95% CI = 0.6 to 2.3) for the same age groups respectively, lower than those calculated using coded data alone. The proportion of records of visible haematuria in coded, rather than uncoded, format was higher in cases than in controls (P<0.002, χ² test). There was no evidence for such differential recording of non-visible haematuria by case/control status (P = 0.78), although, overall, the uncoded format was preferred (P<0.001).

Conclusion

Both non-visible and visible haematuria are associated with bladder cancer, although the visible form confers nearly twice the risk of cancer compared with the non-visible form. GPs’ style of record keeping varies by symptom and possible diagnosis.     

Willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Meru District,Arusha Region,Northern Tanzania

BackgroundThe ability for women to self-collect human papillomavirus (HPV) samples can potentially reduce the risk of cervical cancer and increase screening coverage.ObjectivesTo assess the willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Arusha region, northern Tanzania.MethodsA hospital-based cross-sectional study was conducted among 706 women aged 18–55 years in Meru District Hospital and Usa River Health Centre from March to April 2019. Face-to-face intervies were conducted using a questionnaire. Data analysis was performed using Stata version 14.0. The log-binomial regression was used to determine factors associated with willingness to self-collection of HPV samples.ResultsMajority (70%) of the women were willing to self-collection of HPV samples for cervical cancer screening and was associated with attending Meru District hospital (PR=2.02, 95%CI 1.77–2.31); good knowledge about cervical cancer warning signs (PR=1.11, 95%CI 1.01–1.22), prevention (PR=1.13, 95%CI 1.04–1.20), and symptoms (PR=1.61, 95%CI 1.33–1.93); and having formal employment (PR=1.22, 95%CI 1.07–1.37).ConclusionThe majority of women were willing to self-collect HPV samples for cervical cancer screening. Self-collection is, therefore, an acceptable and viable means of screening for cervical cancer, which has great implications for Tanzania from a health policy perspective.     

Prevalence of Giardia intestinalis and Hymenolepis nana in Afghan refugee population of Mianwali district,Pakistan

Background

Present study aimed to investigate prevalence of Giardia intestinalis and Hymenolepis nana in Afghan refugees visiting Central Health Unit (CHU), Kot Chandana (Mianwali, Northern Punjab) during two years period (February 2007 to December 2009).

Methods

A total of 687 stool samples were collected from different age groups of both genders. Samples were processed under sterile conditions after gross examination. Microscopic examination was done on same day along with eggs (H. nana), cyst and trophozoites (G. intestinalis) detection after staining.

Results

The prevalence of G. intestinalis was significantly higher (x2=59.54, p<0.001) than that of H. nana. Females were found more likely to be infected as compared to males (OR: 1.40, 95% CI=1.03–1.92). Prevalence of both parasites decreased with age and highest prevalence was observed in young individuals belonging to 1–15 years of age group (41.8% and 48.7% respectively for H. nana and G. intestinalis, p<0.001). Abdominal distress (OR: 1.13, 95%CI=0.83–1.53), vomiting (OR: 1.13, 95%CI=1.13–1.81) and rectal prolapse (OR: 4.26, 95%CI=1.38–13.16) were the gastro-intestinal clinical symptoms observed in G. intestinalis. Whereas, bloody diarrhea (OR: 1.56, 95%CI=1.00–2.43) and rectal prolapse (OR: 5.79, 95%CI=1.87–17.91) were associated with H. nana infections.

Conclusions

Intestinal parasitic infections are common among Afghan refugees and serious preventive measures should be implemented to promote the safety and healthy lifestyle of these people.     

Prevalence and associated factors of pneumonia among under-fives with acute respiratory symptoms: a cross sectional study at a Teaching Hospital in Bushenyi District,Western Uganda

ObjectivesThis study assessed the prevalence and associated factors of pneumonia among children under-five years presenting with acute respiratory symptoms.MethodologyThis was a cross sectional study at the Pediatric Department of Kampala International University – Teaching Hospital, from the month of April to August 2019. The study included 336 children aged 2 to 59 months presenting with acute respiratory symptoms to the pediatric clinic. Pneumonia diagnosis was made according to the World Health Organization definition, modified by a chest radiograph. Structured questionnaires were used to collect data on socio-demographic, environmental and nutrition factors and multivariate logistic regression analysis using STATA version 13.0 was done to assess for the factors independently associated with pneumonia.ResultsOf the 336 children with acute respiratory symptoms, eighty-six, 86 (25.6%) had pneumonia. Factors significantly associated with pneumonia included: age below 6 months (OR=3.2, 95%CI=1.17–8.51, p=0.023), rural residence (OR=5.7, 95%CI=2.97–11.05, p <0.001), not up-to-date for age immunization status (OR=2.9, 95%CI=1.05–7.98, p=0.039), severe acute malnutrition (OR=10.8, 95%CI=2.01–58.41, p=0.006), lack of exclusive breastfeeding during the first six months (OR=2.9, 95%CI=1.53–5.53, p=0.001) and exposure to cigarette smoke (OR=3.0, 95%CI=1.35–6.80, p=0.007).ConclusionThe prevalence of pneumonia in children under-five years was high. Most of the factors associated with pneumonia are modifiable; addressing these factors could reduce this prevalence.     

Risk Factors for the Development of Extended-Spectrum Beta-Lactamase-Producing Bacteria in Nonhospitalized Patients

Although the risk factors for acquiring infection by extended-spectrum beta-lactamase (ESBL)-producing bacteria have been investigated in hospitalized patients, such risk factors have not been defined in the community setting. In this study, clinical data from a total of 311 nonhospitalized patients with community-acquired urinary tract infection (128 with ESBL-positive strains and 183 with ESBL-negative strains) were obtained. According to a multivariate analysis, the following were identified as independent risk factors: previous hospitalization in the past 3 months (OR=8.95, 95%CI, 3.77–21.25), antibiotic treatment in the past 3 months (OR=3.23, 95%CI, 1.76–5.91), age over 60 years (OR=2.65, 95%CI, 1.45–4.83), diabetes (OR=2.57, 95%CI, 1.20–5.51), male gender (OR=2.47, 95%CI, 1.22–5.01), Klebsiella pneumoniae infection (OR=2.31, 95%CI, 1.17–4.54), previous use of third-generation cephalosporins (P=0.014, OR=15.8, 95%CI, 1.7–143), previous use of second-generation cephalosporins (P<0.0001, OR=10.1, 95%CI, 4.2–24), previous use of quinolones (P=0.001, OR=4.1, 95%CI, 1.8–9.0), and previous use of penicillin (P=0.003, OR=4.0, 95%CI, 1.6–9.0).     

Glutathione S-transferase P1 Ile105Val Polymorphism and Oral Cancer Risk: A Meta-Analysis

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk.Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I²=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I²=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I²=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I²=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I²=39.7%, p for heterogeneity=0.174).Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.     

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.     

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.     

Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.     

Inhaled Corticosteroid and Secondary Glaucoma: A Meta-analysis of 18 Studies

PurposeGuidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it.MethodsWe performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method.ResultsOut of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86–1.04; P = 0.26; I ² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65–1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23–14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50–2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, −0.19–0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, −0.24–0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28–0.96) suggested a reverse association between ICS and glaucoma.ConclusionsThe ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated.Trial RegistrationUniversity Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351     

Association of a common genetic variant in prostate stem cell antigen with cancer risk

Introduction

Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general.

Material and methods

To evaluate the role of PSCA rs2294008 (C>T) genotype in global cancer, we performed a pooled analysis of all the available published studies involving 22,817 cancer patients and 27,753 control subjects.

Results

The results showed evidence that PSCA rs2294008 (C>T) was associated with increased total cancer risk in the overall comparisons. Stratified analysis by cancer type indicated that PSCA rs2294008 T is associated with increased risk of gastric cancer (OR = 1.24, 95% CI = 1.09–1.42, p_{heterogeneity} < 0.001, I² = 88.0%) and bladder cancer (OR = 1.07, 95% CI = 1.04–1.11, p_{heterogeneity} = 0.108, I² = 55.0%) by allelic contrast. Furthermore, in stratified analysis by histological types of gastric cancer, this PSCA variant showed significant associations with diffuse type (OR = 1.81, 95% CI = 1.16–2.81, p_{heterogeneity} < 0.001, I² = 88.9%) but not intestinal type (OR = 1.29, 95% CI = 0.95–1.74, p_{heterogeneity} < 0.001, I² = 85.2%) in a dominant genetic model. Similar results were found in Asian and European descendents and population-based studies.

Conclusions

In all, our meta-analysis suggests that PSCA rs2294008 (C>T) may play allele-specific roles in cancer development. Further prospective studies with larger numbers of participants worldwide should be performed in different kinds of cancer and other descendents in more detail.     

Relationship Between Androgen Deprivation Therapy for Prostate Cancer and Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis

BackgroundSeveral cohort studies have explored the relationship between androgen deprivation therapy (ADT) and the severity of coronavirus disease 2019 (COVID-19). This study aimed to characterize the relationship between ADT and the severity of COVID-19 in patients with prostate cancer.MethodsA systematic search was conducted using PubMed, Embase, and Cochrane Library databases from the inception of each database until February 31, 2020. Patients with prostate cancer who were treated with ADT were assigned to treatment group while those patients who were not treated with ADT were assigned to the control group. Outcomes were severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) positivity, hospitalization, intensive care unit (ICU) admission, and death. The risk of bias was evaluated using ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) tool.ResultsThree studies with qualitative synthesis were included. Finally, two studies with quantitative synthesis having a total of 44,213 patients were included for the present systematic review. There was no significant difference in SARS-CoV-2 positive rate (odds ratio [OR], 0.52; 95% confidence intervals [Cis], 0.13–2.09; P = 0.362), hospitalization (OR, 0.52; 95% CIs, 0.07–3.69; P = 0.514), ICU admission (OR, 0.93; 95% CIs, 0.39–2.23, P = 0.881), or death (OR, 0.88; 95% CIs, 0.06–12.06; P = 0.934) between ADT and non-ADT groups.ConclusionQualitative and quantitative analyses of previous studies revealed no significant effect of ADT on COVID-19. However, more studies with higher quality that explore biochemical and immunological factors involved are needed to confirm this finding in the future.     

散发性结直肠癌易感性与MTDH/AEG-1基因5’-UTR多态性的关系研究

目的:利用TaqMan-MGB荧光探针法分析MTDH/AEG-1基因5’-UTR多态性与中国南方地区散发性结直肠癌(colorectal cancer,CRC)易感性的关系。方法:采用病例对照法,收集华南地区693例散发性结直肠癌患者及660例健康人血液DNA,利用TaqMan-MGB探针法检测MTDH/AEG-1基因5’-UTR区多态性。结果:MTDH/AEG-1基因5’-UTR区多态性位点-1 913C/G、-797G/A等位基因分布在结直肠癌患者人群与健康对照组中无显著差异。但-1 913C/G突变纯合子GG可显著增加饮酒者(OR=1.71,95%CI=1.13-2.57)及女性(OR=1.48,95%CI=1.01-2.17)罹患结直肠癌的风险,-1 913GG与饮酒及女性性别在增加结直肠癌发病风险上存在交互作用(P0.01);-797G/A突变基因型(GA+AA)可增加饮酒者(OR=1.55,95%CI=1.06-2.27)及肿瘤家族史人群(OR=3.48,95%CI=1.60-7.57)的结直肠癌发病风险,-797G/A突变与饮酒及肿瘤家族史在增加结直肠癌罹患风险上具有交互作用(P0.01)。2个多态性位点与年龄、吸烟、肥胖均无交互作用。结论:MTDH/AEG-1基因5’-UTR区单核苷酸多态性与结直肠癌发病无明显相关性,但其与饮酒、性别及肿瘤家族史因素在增加结直肠癌罹患率上具有交互作用。