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Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient's transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response.
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Doxazossina , Finasterida , Próstata , Hiperplasia Prostática , Humanos , Finasterida/farmacologia , Finasterida/uso terapêutico , Masculino , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Doxazossina/uso terapêutico , Doxazossina/farmacologia , Doxazossina/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Idoso , Inibidores de 5-alfa Redutase/farmacologia , Inibidores de 5-alfa Redutase/uso terapêutico , Pessoa de Meia-IdadeRESUMO
Background: Prostate cancer is one of the leading causes of cancer-related mortality among men in the United States. We examined the role of neighborhood obesogenic attributes on prostate cancer risk and mortality in the Southern Community Cohort Study (SCCS). Methods: From the total of 34,166 SCCS male participants, 28,356 were included in the analysis. We assessed the relationship between neighborhood obesogenic factors [neighborhood socioeconomic status (nSES) and neighborhood obesogenic environment indices including the restaurant environment index, the retail food environment index, parks, recreational facilities, and businesses] and prostate cancer risk and mortality by controlling for individual-level factors using a multivariable Cox proportional hazards model. We further stratified prostate cancer risk analysis by race and body mass index (BMI). Results: Median follow-up time was 133 months [interquartile range (IQR): 103, 152], and the mean age was 51.62 (SD: ± 8.42) years. There were 1,524 (5.37%) prostate cancer diagnoses and 98 (6.43%) prostate cancer deaths during follow-up. Compared to participants residing in the wealthiest quintile, those residing in the poorest quintile had a higher risk of prostate cancer (aHR = 1.32, 95% CI 1.12-1.57, p = 0.001), particularly among non-obese men with a BMI < 30 (aHR = 1.46, 95% CI 1.07-1.98, p = 0.016). The restaurant environment index was associated with a higher prostate cancer risk in overweight (BMI ≥ 25) White men (aHR = 3.37, 95% CI 1.04-10.94, p = 0.043, quintile 1 vs. None). Obese Black individuals without any neighborhood recreational facilities had a 42% higher risk (aHR = 1.42, 95% CI 1.04-1.94, p = 0.026) compared to those with any access. Compared to residents in the wealthiest quintile and most walkable area, those residing within the poorest quintile (aHR = 3.43, 95% CI 1.54-7.64, p = 0.003) or the least walkable area (aHR = 3.45, 95% CI 1.22-9.78, p = 0.020) had a higher risk of prostate cancer death. Conclusion: Living in a lower-nSES area was associated with a higher prostate cancer risk, particularly among Black men. Restaurant and retail food environment indices were also associated with a higher prostate cancer risk, with stronger associations within overweight White individuals. Finally, residing in a low-SES neighborhood or the least walkable areas were associated with a higher risk of prostate cancer mortality.
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Background: Prostate cancer is one of the leading causes of cancer-related mortality among men in the United States. We examined the role of neighborhood obesogenic attributes on prostate cancer risk and mortality in the Southern Community Cohort Study (SCCS). Methods: From the total of 34,166 SCCS male participants, 28,356 were included in the analysis. We assessed the relationship between neighborhood obesogenic factors [neighborhood socioeconomic status (nSES) and neighborhood obesogenic environment indices including the restaurant environment index, the retail food environment index, parks, recreational facilities, and businesses] and prostate cancer risk and mortality by controlling for individual-level factors using a multivariable Cox proportional hazards model. We further stratified prostate cancer risk analysis by race and body mass index (BMI). Results: Median follow-up time was 133 months [interquartile range (IQR): 103, 152], and the mean age was 51.62 (SD: ± 8.42) years. There were 1,524 (5.37%) prostate cancer diagnoses and 98 (6.43%) prostate cancer deaths during follow-up. Compared to participants residing in the wealthiest quintile, those residing in the poorest quintile had a higher risk of prostate cancer (aHR = 1.32, 95% CI 1.12-1.57, p = 0.001), particularly among non-obese men with a BMI < 30 (aHR = 1.46, 95% CI 1.07-1.98, p = 0.016). The restaurant environment index was associated with a higher prostate cancer risk in overweight (BMI ≥ 25) White men (aHR = 3.37, 95% CI 1.04-10.94, p = 0.043, quintile 1 vs. None). Obese Black individuals without any neighborhood recreational facilities had a 42% higher risk (aHR = 1.42, 95% CI 1.04-1.94, p = 0.026) compared to those with any access. Compared to residents in the wealthiest quintile and most walkable area, those residing within the poorest quintile (aHR = 3.43, 95% CI 1.54-7.64, p = 0.003) or the least walkable area (aHR = 3.45, 95% CI 1.22-9.78, p = 0.020) had a higher risk of prostate cancer death. Conclusion: Living in a lower-nSES area was associated with a higher prostate cancer risk, particularly among Black men. Restaurant and retail food environment indices were also associated with a higher prostate cancer risk, with stronger associations within overweight White individuals. Finally, residing in a low-SES neighborhood or the least walkable areas were associated with a higher risk of prostate cancer mortality.
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BACKGROUND: We previously reported that outcomes after radical prostatectomy (RP) were similar among non-Hispanic Black, non-Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP. METHODS: Analysis included men in SEARCH cohort who underwent RP (1988-2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration-resistant PC (CRPC), and PC-specific mortality (PCSM). RESULTS: Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings. CONCLUSIONS: In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post-treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Extensão Extranodal , Neoplasias da Próstata/patologia , Prostatectomia/métodos , Resultado do Tratamento , Antígeno Prostático Específico , Hispânico ou Latino , Recidiva Local de Neoplasia/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Cutaneous melanomas (CMs) are more frequently found on the trunk in men, and on the hip and lower extremities (legs) in women. This discrepancy has been attributed to greater exposure to ultraviolet (UV) radiation of women's legs due to their dressing habits. OBJECTIVES: To understand the sex difference in the bodily distribution of CMs, especially those on the legs. METHODS: This was a cancer registry-based cohort study. CM incidences, relative tumour density and tumour mutational burdens (TMBs) were compared among different body sites in different sex and racial groups using the SEER (Surveillance, Epidemiology, and End Results) and TCGA SKCM (The Cancer Genome Atlas skin cutaneous melanoma) databases. RESULTS: White men had lower rates and lower relative tumour density (RTD) of CMs on their legs compared with the rest of their body sites, or compared with White women. Men classified by SEER into racial groups other than White did not show such a trend. White women had comparable RTDs among different body sites. The ratios between the 'White' and the 'other' groups were used to evaluate the approximate effect of sun exposure at different body sites, which further validated a distinct protective effect of men's legs in melanoma. TMB on leg melanomas was lower than on other sites in both sexes. CONCLUSIONS: The legs of both sexes in White patients show lower RTDs and lower levels of TMB, suggesting a weaker association with UV exposure. Furthermore, White men are especially protected against CM on their legs, suggesting an unknown intrinsic protective factor as compared with women.
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Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Masculino , Melanoma/patologia , Neoplasias Cutâneas/patologia , Incidência , Estudos de Coortes , Extremidade Inferior/patologiaRESUMO
Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are more likely to be diagnosed with aggressive/potentially lethal PCa and have shorter disease-free survival. Expression of a truncated AR in an aggressively growing patient-derived xenograft developed with a primary PCa specimen from an AA patient led us to hypothesize that the expression of AR-SVs could be an indicator of aggressive growth both in PCa progression and at the CRPC stage in AA men. Tissue microarrays (TMAs) were created from formalin-fixed paraffin-embedded (FFPE) prostatectomy tumor blocks from 118 AA and 115 CA treatment-naïve PCa patients. TMAs were stained with AR-V7-speicifc antibody and with antibodies binding to the N-terminus domain (NTD) and ligand-binding domain (LBD) of the AR. Since over 20 AR-SVs have been identified, and most AR-SVs do not as yet have a specific antibody, we considered a 2.0-fold or greater difference in the NTD vs. LBD staining as indication of potential AR-SV expression. Two AA, but no CA, patient tumors stained positively for AR-V7. AR staining with NTD and LBD antibodies was robust in most patients, with 21% of patients staining at least 2-fold more for NTD than LBD, indicating that AR-SVs other than AR-V7 are expressed in primary treatment-naïve PCa. About 24% of the patients were AR-negative, and race differences in AR expression were not statistically significant. These results indicate that AR-SVs are not restricted to CRPC, but also are expressed in primary PCa at higher rate than previously reported. Future investigation of the relative expression of NTD vs. LBD AR-SVs could guide the use of newly developed treatments targeting the NTD earlier in the treatment paradigm.
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PURPOSE: Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race. METHODS: Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested. RESULTS: Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25). CONCLUSION: Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.
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Síndrome Metabólica , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Síndrome Metabólica/epidemiologia , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico , ObesidadeRESUMO
BACKGROUND: Previous experimental studies showed that limiting methionine in the diet of animals or in cell culture media suppresses mammary cancer cell proliferation or metastasis. However, no previous study has investigated the associations of changes in methionine intake with survival among breast cancer survivors. We aimed to examine the association between changes in dietary intake of methionine, folate/folic acid, and vitamin B12 from before to after diagnosis of breast cancer, and mortality among breast cancer survivors. METHODS: We included 1553 postmenopausal women from the Women's Health Initiative who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after breast cancer diagnosis. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence (CIs) of all-cause and breast cancer mortality associated with changes in methionine intake and changes in folate/folic acid and vitamin B12 intake. RESULTS: Relative to pre-diagnosis, 28% of women decreased methionine intake by ≥20%, 30% of women increased methionine intake by ≥20%, and 42% of women had a relatively stable methionine intake (±19.9%) following breast cancer diagnosis. During a mean 16.1 years of follow up, there were 772 deaths in total, including 195 deaths from breast cancer. Compared to women with relatively stable methionine intake, women with decreased methionine intake had lower risks of all-cause (HR 0.78, 95% CI 0.62-0.97) and breast cancer mortality (HR 0.58, 95% CI 0.37-0.91) in fully adjusted models. In contrast, increased methionine intake or changes in folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality. CONCLUSIONS: Among breast cancer survivors, decreased methionine intake after breast cancer diagnosis was associated with lower risk of all-cause and breast cancer mortality.
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Neoplasias , Vitamina B 12 , Feminino , Animais , Ácido Fólico/metabolismo , Metionina/metabolismo , Pós-Menopausa , Estudos Prospectivos , Fatores de Risco , Racemetionina , Ingestão de AlimentosRESUMO
BACKGROUND: Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms. OBJECTIVES: The study aimed to systematically identify prenatal metabolomic profiles mediating the intergenerational transmission of obesity. METHODS: We included 450 African-American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study pregnancy cohort. LC-MS was used to conduct metabolomic profiling on maternal plasma samples of the second trimester. The childhood growth outcomes of interest included BMI trajectories from birth to age 4 y (rising-high-, moderate-, and low-BMI trajectories) as well as overweight/obesity (OWO) risk at age 4 y. Mediation analysis was conducted to identify metabolite mediators linking maternal OWO and childhood growth outcomes. The potential causal effects of maternal OWO on metabolite mediators were examined using the Mendelian randomization (MR) method. RESULTS: Among the 880 metabolites detected in the maternal plasma during pregnancy, 14 and 11 metabolites significantly mediated the effects of maternal prepregnancy OWO on childhood BMI trajectories and the OWO risk at age 4 y, respectively, and 5 mediated both outcomes. The MR analysis suggested 6 of the 20 prenatal metabolite mediators might be causally influenced by maternal prepregnancy OWO, most of which are from the pathways related to the metabolism of amino acids (hydroxyasparagine, glutamate, and homocitrulline), sterols (campesterol), and nucleotides (N2,N2-dimethylguanosine). CONCLUSIONS: Our study provides further evidence that prenatal metabolomic profiles might mediate the effect of maternal OWO on early childhood growth trajectories and OWO risk in offspring. The metabolic pathways, including identified metabolite mediators, might provide novel intervention targets for preventing the intrauterine development of obesity in the offspring of mothers with obesity.
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Obesidade Materna , Obesidade Infantil , Efeitos Tardios da Exposição Pré-Natal , Pré-Escolar , Humanos , Feminino , Gravidez , Obesidade Infantil/etiologia , Obesidade Materna/complicações , Índice de Massa Corporal , Estudos Prospectivos , Sobrepeso/complicações , VitaminasRESUMO
OBJECTIVES: Ureteral stents are commonly used during pyeloplasty to ensure drainage and anastomotic healing. Antibiotic prophylaxis is often used due to concerns for urinary tract infection (UTI). Although many surgeons prescribe prophylactic antibiotics following pyeloplasty, practices vary widely due to lack of clear evidence-based guidelines. We hypothesize that the rate of stent UTI does not significantly vary between children who receive antibiotics and those who do not. METHODS: We reviewed the medical records of 741 patients undergoing pyeloplasty between January 2010 and July 2018 across seven institutions. Exclusion criteria were: age older than 22 years, no stent placed, externalized stents used, and incomplete records. Surgical approach, age, antibiotic use, stent duration, Foley duration, and urine culture results were recorded. Patients were categorized into two groups, those younger than four years of age and those four years and older as proxy for likely diaper use. Univariate logistic regression was conducted to identify variables associated with UTI. Multivariable backward stepwise logistic regression was used to identify the best model with Akaike information criterion as model selection criteria. The selected model was used to calculate odds ratios and 95% confidence intervals summarizing the association between prophylactic antibiotics and stent UTI while controlling for age, gender, and intra-operative urine cultures. RESULTS: 672 patients were included; 338 received antibiotic prophylaxis and 334 did not. These groups differed in mean age (3.91 vs. 6.91 years, P < .001), mean stent duration (38.5 vs. 35.32 days, P < .001), and surgical approach (53.25% vs. 32.04% open vs. laparoscopic, P < .001). The incidence of stent UTI was low overall (7.59%) and similar in both groups: 31/338 (9.17%) in the prophylaxis group and 20/334 (5.99%) in the non-prophylaxis group (P = .119). Although female gender, likely diaper use, and positive intra-operative urine culture were each associated with significantly higher odds of stent UTI, prophylactic antibiotic use was not associated with significant reduction in stent UTI in any of these groups. Surgical approach, stent duration, and Foley duration were not associated with stent UTI. CONCLUSION: Incidence of stent UTI is low overall following pyeloplasty. Prophylactic antibiotics are not associated with lower rates of stent UTI following pyeloplasty even after controlling for risk factors of female gender, likely diaper use, and positive intra-operative urine culture. Routine administration of prophylactic antibiotics after pyeloplasty does not appear to be beneficial, and may be best reserved for those with multiple risk factors for UTI.
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Laparoscopia , Ureter , Infecções Urinárias , Humanos , Criança , Feminino , Adulto Jovem , Adulto , Ureter/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Stents/efeitos adversos , Laparoscopia/efeitos adversos , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Infecções Urinárias/epidemiologia , Antibacterianos/uso terapêutico , Estudos RetrospectivosRESUMO
A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10-4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10-5; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10-4; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.
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Detecção Precoce de Câncer , Neoplasias da Próstata , Estudos de Casos e Controles , Predisposição Genética para Doença , Células Germinativas/patologia , Mutação em Linhagem Germinativa , Proteínas de Homeodomínio/genética , Humanos , Masculino , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. MATERIALS AND METHODS: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. RESULTS: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings. CONCLUSION: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.
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População Negra , Cromossomos Humanos Par 8 , Predisposição Genética para Doença , Herança Multifatorial , Neoplasias da Próstata , População Negra/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 8/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Medição de Risco , População Branca/genéticaRESUMO
METHODS: Patients were identified using a retrospective cohort analysis from a single, tertiary care, urban children's hospital. Patients presenting directly to our emergency department aged 2 to 18 years were included if they had a diagnosis of severe asthma exacerbation, defined by an initial Respiratory Clinical Score (RCS) of 9 or higher. A total of 787 patients were identified during the study timeframe (December 16, 2017, to December 31, 2018), and of those, 651 patients met study criteria and were included in the analysis. The χ2 test was used to establish P values for categorical variables. For normally distributed variables, a t test was used. For nonnormally distributed variables, the Kruskal-Wallis test was used. A P value of 0.05 or less was interpreted as statistically significant. RESULTS: Patients who received terbutaline had an increased risk of admission to the PICU (P < 0.001). This association was lost after controlling for age, sex, continuous albuterol use, and intramuscular epinephrine use (P = 0.362). Patients receiving terbutaline in the emergency department also had a higher risk of admission to the hospital (odds ratio, 1.55; confidence interval, 1.08-2.22; P = 0.020) as compared with their nonterbutaline counterparts. Overall, patients in the terbutaline group had a higher initial RCS at presentation. Upon further analysis, patients with the same RCS at presentation were more likely to be admitted if they received terbutaline than those who did not. There was no statistically significant difference in length of stay (P = 0.298) and BiPAP/CPAP use (P = 0.107). The patients on terbutaline were relatively more likely to require oxygen (P = 0.003) and intramuscular epinephrine (P = 0.010) than the patients not on terbutaline. CONCLUSIONS: Terbutaline administration given to pediatric patients experiencing a severe asthma exacerbation was not associated with decreased PICU or general hospital floor admission. The study is limited given that it was a retrospective analysis. Further randomized controlled trials are needed to assess the role of terbutaline in severe acute asthma exacerbations in pediatric patients.
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Asma , Terbutalina , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Criança , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Terbutalina/uso terapêuticoRESUMO
The associations of testosterone therapy (TTh) and statins use with prostate cancer remain conflicted. However, the joint effects of TTh and statins use on the incidence of prostate cancer, stage and grade at diagnosis, and prostate cancer-specific mortality (PCSM) have not been studied.We identified White (N = 74,181), Black (N = 9,157), and Hispanic (N = 3,313) men diagnosed with prostate cancer in SEER-Medicare 2007-2016. Prediagnostic prescription of TTh and statins was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models evaluated the association of TTh and statins with prostate cancer, including statistical interactions between TTh and statins.We found that TTh (OR = 0.74; 95% CI, 0.68-0.81) and statins (OR = 0.77; 95% CI, 0.0.75-0.88) were inversely associated with incident prostate cancer. Similar inverse associations were observed with high-grade and advanced prostate cancer in relation to TTh and statins use. TTh plus statins was inversely associated with incident prostate cancer (OR = 0.53; 95% CI, 0.48-0.60), high-grade (OR = 0.43; 95% CI, 0.37-0.49), and advanced prostate cancer (OR = 0.44; 95% CI, 0.35-0.55). Similar associations were present in White and Black men, but among Hispanics statins were associated with PCSM.Prediagnostic use of TTh or statins, independent or combined, was inversely associated with incident and aggressive prostate cancer overall and in NHW and NHB men. Findings for statins and aggressive prostate cancer are consistent with previous studies. Future studies need to confirm the independent inverse association of TTh and the joint inverse association of TTh plus statins on risk of prostate cancer in understudied populations. PREVENTION RELEVANCE: The study investigates a potential interaction between TTh and statin and its effect on incident and aggressive prostate cancer in men of different racial and ethnic backgrounds. These results suggest that among NHW and non-Hispanic Black men TTh plus statins reduced the odds of incident prostate cancer, high-grade and advance stage prostate cancer.
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Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Neoplasias da Próstata/epidemiologia , Testosterona/administração & dosagem , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Hispânico ou Latino/estatística & dados numéricos , Terapia de Reposição Hormonal/métodos , Humanos , Incidência , Masculino , Medicare/estatística & dados numéricos , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/prevenção & controle , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Estados Unidos , População Branca/estatística & dados numéricosRESUMO
OBJECTIVE: Prenatal metabolomics profiles, providing measures of in utero nutritional and environmental exposures, may improve the prediction of childhood outcomes. We aimed to identify prenatal plasma metabolites associated with early childhood body mass index (BMI) trajectories and overweight/obesity risk in offspring. METHODS: This study included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study. An untargeted metabolomics analysis was performed on the mothers' plasma samples collected during the second trimester. The children's BMI-z-score trajectories from birth to age 4 [rising-high- (9.8%), moderate- (68.2%), and low-BMI (22.0%)] and overweight/obesity status at age 4 were the main outcomes. The least absolute shrinkage and selection operator (LASSO) was used to select the prenatal metabolites associated with childhood outcomes. RESULTS: The mothers were 24.5 years old on average at recruitment, 76.4% having education less than 12 years and 80.0% with Medicaid or Medicare. In LASSO, seven and five prenatal metabolites were associated with the BMI-z-score trajectories and overweight/obese at age 4, respectively. These metabolites are mainly from/relevant to the pathways of steroid biosynthesis, amino acid metabolism, vitamin B complex, and xenobiotics metabolism (e.g., caffeine and nicotine). The odds ratios (95% CI) associated with a one SD increase in the prenatal metabolite risk scores (MRSs) constructed from the LASSO-selected metabolites were 2.97 (1.95-4.54) and 2.03 (1.54-2.67) for children being in the rising-high-BMI trajectory group and overweight/obesity at age 4, respectively. The MRSs significantly improved the risk prediction for childhood outcomes beyond traditional prenatal risk factors. The increase (95% CI) in the area under the receiver operating characteristic curves were 0.10 (0.03-0.18) and 0.07 (0.02-0.12) for the rising-high-BMI trajectory (P = 0.005) and overweight/obesity at age 4 (P = 0.007), respectively. CONCLUSIONS: Prenatal metabolomics profiles advanced prediction of early childhood growth trajectories and obesity risk in offspring.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Metaboloma/fisiologia , Obesidade Infantil/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metabolômica , Gravidez , Adulto JovemRESUMO
PURPOSE: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men. METHODS: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders. RESULTS: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP. CONCLUSION: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.
Assuntos
Monócitos , Neoplasias da Próstata/imunologia , Negro ou Afro-Americano , Idoso , Bases de Dados Factuais , Hospitais de Veteranos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Veteranos , População BrancaRESUMO
Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.
Assuntos
População Negra/estatística & dados numéricos , Predisposição Genética para Doença , Modelos Genéticos , Herança Multifatorial , Neoplasias da Próstata/epidemiologia , Fatores Etários , População Negra/genética , Estudos de Casos e Controles , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Neoplasias da Próstata/genéticaRESUMO
BACKGROUND: The association of aspirin use with prostate cancer has been investigated, but few studies included African-American men. Here, we analyzed the relationship of aspirin intake with prostate cancer risk and mortality among African-American men in the Southern Community Cohort Study (SCCS). METHODS: SCCS recruited 22,426 African-American men between 2002 and 2009. Aspirin use was assessed at enrollment. Our exposures of interest were any aspirin use (regular strength, low-dose or baby aspirin, or half tablets of aspirin) and regular strength aspirin. Each exposure variable was compared with nonusers. Associations between aspirin use and prostate cancer risk and mortality were examined with Cox proportional hazards models. RESULTS: At enrollment, 5,486 men (25.1%) reported taking any aspirin and 2,634 men (12.1%) reported regular strength aspirin use. During follow-up (median, 13 years), 1,058 men developed prostate cancer, including 103 prostate cancer-specific deaths. Aspirin use was not associated with prostate cancer development [adjusted HR, 1.07; 95% confidence interval (CI), 0.92-1.25 for any aspirin use and HR, 0.97; 95% CI, 0.78-1.19 for regular strength aspirin], but was suggestively associated with reduced prostate cancer mortality (HR, 0.66; 95% CI, 0.39-1.14 for any aspirin use and HR, 0.41; 95% CI, 0.17-1.00 for regular strength aspirin). CONCLUSIONS: Aspirin use at enrollment was tentatively associated with reduced prostate cancer mortality, but not risk, among African-American men in SCCS. IMPACT: Prospective SCCS data suggest that aspirin use may help prevent lethal prostate cancer among this high-risk group of men.
Assuntos
Aspirina/efeitos adversos , Neoplasias da Próstata/induzido quimicamente , Negro ou Afro-Americano , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/mortalidade , Análise de SobrevidaRESUMO
Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.
Assuntos
Células Germinativas , Neoplasias da Próstata/genética , Idoso , População Negra , Hotspot de Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Medição de RiscoRESUMO
AIMS: The aim of this study is to identify factors associated with urinary incontinence (UI) in a community sample of young nulligravid women. METHODS: This was a secondary analysis from a cross-sectional survey-based study of cisgender women aged 18 to 25 years recruited through a national registry of research volunteers. Participants completed validated questionnaires assessing toileting behaviors, lower urinary tract symptoms (LUTS), and bowel symptoms. Women were excluded from analysis if currently pregnant, any prior pregnancy, cystectomy, or any neurologic disease including spinal cord injury, stroke, or multiple sclerosis. Analyses determined the prevalence of symptoms and evaluated candidate risk factors for UI. RESULTS: Final analyses included 964 women (mean age, 22.6 ± 2.0). Monthly UI was identified in 295 (30.6%) subjects, with mixed UI being the most common (56.9%; n = 168). Seventy-two women (7.4%) reported fecal incontinence (FI) and 24 (3.5%) women reported both UI and FI. After multivariable regression modeling, UI was associated with an intermittent urine stream and the delayed voiding toileting behavior subscale. CONCLUSIONS: UI in this cohort of young nulliparous women was highly prevalent and warrants further study as to the cause. Therapeutic guidelines to prevent UI and LUTS may need to be adjusted by targeting populations earlier than traditionally considered.