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OBJECTIVES: Pediatric diabetic ketoacidosis (DKA) is often treated in a PICU, but nonsevere DKA may not necessitate PICU admission. At our institution, nonsevere DKA was treated on the floor until policy change shifted care to the PICU. We describe outcomes in pediatric mild to moderate DKA by treatment location. METHODS: Patients aged 2 to 21 with mild to moderate DKA (pH <7.3 but >7.1), treated on the floor from January 1, 2018 to July 31, 2020 and PICU from August 1, 2020 to October 1, 2022 were included. We performed a single-center, retrospective cohort study; primary outcome was DKA duration (from emergency department diagnosis to resolution), secondary outcomes included hospital length of stay, and complication rates, based on treatment location. RESULTS: Seventy nine floor and 65 PICU encounters for mild to moderate pediatric DKA were analyzed. There were no differences in demographics, initial pH, or bicarbonate; PICU patients had more acute kidney injury on admission. Floor patients had a shorter DKA duration (10 hours [interquartile range 7-13] vs 11 hours [9-15]; P = .04), and a shorter median length of stay (median 43.5 hours [interquartile range 31-62] vs 49 hours [32-100]; P < .01). No patients had clinical signs of cerebral edema; other complications occurred at similar rates. PICU patients received significantly more intravenous electrolyte boluses, but there were no differences in dysrhythmia or electrolyte abnormalities on final serum chemistry. CONCLUSIONS: Our study did not find a clear benefit to admitting patients with mild to moderate DKA to the PICU instead of the hospital floor. Our findings suggest that some children with nonsevere DKA may be treated safely in a non-PICU setting.
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Cetoacidose Diabética , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação , Humanos , Cetoacidose Diabética/terapia , Estudos Retrospectivos , Criança , Feminino , Masculino , Adolescente , Pré-Escolar , Tempo de Internação/estatística & dados numéricos , Adulto Jovem , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To investigate the cadence of recurrence in patients with low grade intermediate-risk non-muscle invasive bladder cancer (LG IR-NMIBC) based on clinical determinants. We aim to describe patterns in rates of recurrence to better inform surveillance regimens for this chronic, burdensome, and costly disease. METHODS: Using baseline and follow-up data from participants in the West Midlands' (United Kingdom, UK) Bladder Cancer Prognosis Programme (BCPP), we assessed overall recurrence rate and recurrence-free intervals throughout the follow-up period for IR-NMIBC participants. Recurrence-free intervals were calculated using the Kaplan-Meier method. RESULTS: We identified 379 patients with G1/G2 pTa tumors classified as intermediate risk. Median age was 70 and 284/379 (75%) were male. The median follow-up time was 4.2 years (95% CI: 3.9-4.8). After 5 years of follow-up, 53% of patients had at least one recurrence. One-year recurrence-free survival (RFS) was 75% and 4-year RFS was 50%. The median time to or between 1st, 2nd, 3rd, 4th, and 5th sequential recurrences was 49, 19, 12, 14, and 10 months, respectively. CONCLUSION: Over half of patients with IR-NMIBC are destined to recur. Our data suggest that a subset of patients experience acceleration of recurrence over time and that this acceleration may serve as a potential kinetic biomarker for these individuals that could inform surveillance intervals and future treatment strategies.
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PURPOSE: There is not yet satisfactory performance data comparing multiparametric MRI (mpMRI) versus biparametric MRI (bpMRI) for detecting prostate cancer (PCa), particularly in high-risk populations. We compared both protocols for detecting overall PCa and clinically significant PCa (CS-PCa; defined as Grade Group ≥ 2) in a multiethnic urban population. METHODS: We retrospectively reviewed electronic medical record data from men who underwent image-guided fusion prostate biopsy (FB) between 2016 and 2021 at our institution. Patient characteristics, Prostate Imaging Reporting and Data System (PI-RADS) scores, and FB outcomes were analyzed based on MRI protocol. Multivariate mixed-effects logistic regression models were used to examine associations of bpMRI versus mpMRI for detecting overall PCa and CS-PCa in targeted lesions, among all patients and stratified by race/ethnicity. RESULTS: Overall, 566 men (44.0% Non-Hispanic Black [NHB]; 27.0% Hispanic) with 975 PI-RADS 3-5 lesions on MRI underwent FB. Of these, 312 (55%) men with 497 lesions underwent mpMRI and 254 (45%) men with 478 lesions underwent bpMRI. On multivariate analyses among all men, the odds of detecting overall PCa (OR = 1.18, 95% CI: 1.05-3.11, p = 0.031) and CS-PCa (OR = 2.15, 95% CI: 1.16-4.00, p = 0.014) on FB were higher for lesions identified on bpMRI than mpMRI. When stratified by race/ethnicity, the odds of detecting overall PCa (OR = 1.86; p = 0.15) and CS-PCa (OR = 2.20; p = 0.06) were not statistically different between lesions detected on bpMRI or mpMRI. CONCLUSION: BpMRI has similar diagnostic performance to mpMRI in detecting overall and CS-PCa within a racially/ethnically diverse population. BpMRI can be utilized for evaluating suspected CS-PCa among NHB and Hispanic men.
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Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Etnicidade , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , África Subsaariana , Projetos Piloto , Gradação de TumoresRESUMO
OBJECTIVE: To investigate the association between ultraviolet light index (UVI), as a marker for UV exposure, and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained zipcode level UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression models to examine associations between regional UVI (by zipcode)/season and odds of rash and severe SLEDAI-2 K score (≥ 5 vs. 0-4), adjusting for age, sex, race and income. RESULTS: Among 1222 participants, with a mean of 2.3 visits per participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2 K score ≥ 5. There were no associations between UVI during the month prior to visit or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but not increased disease activity. CONCLUSION: This study found no association between UVI and rash or UVI and disease activity. However, further studies directly measuring UV exposure and accounting for patient-level protective behavioral measures may help to better understand the complex relationship between sun exposure and SLE disease activity.
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Exantema , Lúpus Eritematoso Sistêmico , Sistema de Registros , Raios Ultravioleta , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Feminino , Masculino , Criança , Adolescente , Exantema/etiologia , Raios Ultravioleta/efeitos adversos , Índice de Gravidade de Doença , Estações do AnoRESUMO
Objective: To investigate the association between sun exposure measured by ultraviolet light index (UVI) and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods: We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression to examine an association between UVI/season and rash / SLEDAI-2K score, adjusting for age, sex, race and income. Results: Among 1222 participants, with a mean of 2.3 visits/participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2K score ≥ 5. There were no associations between UVI during the month prior to visit, or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but there not increased disease activity. Conclusion: While we found no association between UVI and rash or UVI and disease activity, further studies directly measuring UVI may help further understand whether a relationship exists between sun exposure and SLE disease activity and whether this is an area that continues to require clinical attention.
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Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10-5, r2 < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.
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PURPOSE: Transrectal ultrasound-guided prostate biopsy remains the most used method for the detection of prostate cancer. We recently reported that detection of clinically significant prostate cancer (cs-CaP) using image-guided fusion biopsies (IGFB) varied by race/ethnicity, which calls for further comparison between cognitive fusion biopsy (CFB) and IGFB among non-Hispanic black and Hispanic populations. Therefore, the aim of our study is to compare the rates of detection of cs-CaP and overall CaP by CFB and IGFB in a multiethnic community. MATERIAL AND METHODS: We performed a retrospective, cross-sectional review of men who underwent MRI-transrectal ultrasound-guided prostate biopsy at our diverse, urban academic medical center. Agreement and discordance between fusion biopsies and systematic biopsies for detection of cs-CaP and overall CaP were determined using Kappa statistics. Univariate and multivariate mixed-effects logistic regression models were used to find associations between fusion modalities and prostate cancer detection. RESULTS: In total, 710 men underwent fusion prostate biopsies between December 2015 and June 2021. Upon univariate and multivariate logistic regression analysis, there was no significant association between IGFB vs. CFB and risk of overall CaP (ORâ¯=â¯0.66, 95% CI: 0.36-1.21, Pâ¯=â¯0.18) or cs-CaP (ORâ¯=â¯0.57, 95% CI: 0.30-1.08, Pâ¯=â¯0.09). We found moderate agreement between fusion and systematic biopsies for both CFB (κâ¯=â¯0.56) and IGFB (κâ¯=â¯0.52) in cs-CaP. CONCLUSIONS: CFB and IGFB offer similar detection rates of cs-CaP in a multiethnic population. CFB represents an effective and accessible means of accurately diagnosing prostate cancer.
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Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Estudos Transversais , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Cognição , Ultrassonografia de Intervenção/métodosRESUMO
We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.
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Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.
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BACKGROUND: Chronic kidney disease (CKD) is a major health problem, and the risk of CKD and hypertension in children born low birth weight (LBW) is under-recognized. We hypothesized that children born with LBW would have a higher prevalence of reduced kidney function and hypertension. METHODS: Using the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study to evaluate whether LBW (< 2500 g), very low birth weight (VLBW < 1500 g), and large birth weight (BW) (> 4000 g) were associated with kidney disease using 4 different estimating equations. We used the Counahan-Barratt, updated Schwartz, CKiD-U25, and full age spectrum creatinine-based GFR estimating equations to evaluate associations between a history of LBW/VLBW/large BW and reduced kidney function (eGFR < 90 mL/min/1.73 m2) in children. We also assessed blood pressure (BP) using the old and new pediatric hypertension guidelines. RESULTS: Our analysis included 6336 children (age 12-15 years) in NHANES representing over 13 million US individuals. Using the updated Schwartz, the prevalence of reduced kidney function was 30.1% (25.2-35.6) for children born with LBW compared to 22.4% (20.5-24.3) in children with normal BW. Equations yielded different estimates of prevalence of reduced kidney function in LBW from 21.5% for Counahan-Barratt to 35.4% for CKiD-U25. Compared to those with normal BW, participants with LBW and VLBW had a 7.2 and 10.3% higher prevalence of elevated BP and a 2.4 and 14.6% higher prevalence of hypertension, respectively. CONCLUSIONS: Children born with LBW are at higher risk of reduced kidney function and hypertension than previously described. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Hipertensão , Insuficiência Renal Crônica , Recém-Nascido , Humanos , Criança , Adolescente , Inquéritos Nutricionais , Estudos Transversais , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/diagnóstico , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Hipertensão/epidemiologia , RimRESUMO
INTRODUCTION: This study aimed to evaluate predictors of timely urological evaluation among men referred for initial elevated PSA in a diverse, high-risk, urban community. METHODS: We conducted a retrospective cohort study of all men aged 50+ referred to urology within our healthcare network between January 2018 and December 2021 for initial elevated PSA. Time to initial urological evaluation was categorized as timely (within 4 months of referral), late (after 4 months), or absent (no urology evaluation). Demographic and clinical variables were abstracted. A multivariable multinomial logistic regression model was conducted to identify predictors of timely vs late vs absent urological evaluation controlling for age, referral year, household income, distance to care, and PSA at referral. RESULTS: A total of 1,335 men met inclusion criteria; 589 (44.1%), 210 (15.7%), and 536 (40.1%) had timely, late, and absent urological evaluation, respectively. The majority were non-Hispanic Black (46.7%), English-speaking (84.0%), and married (54.6%). Median time to initial urological evaluation differed significantly between timely and late groups (16 vs 210 days, P < .001). Multivariable logistic regression revealed the following to be significant predictors of timely urological evaluation: non-Hispanic Black (OR=1.59, P = .03), Hispanic (OR=2.07, P = .001), Spanish-speaking (OR=1.44, P = .03), or former-smokers (OR=1.31, P = .04). CONCLUSIONS: In our diverse community, men who are non-Hispanic White or English-speaking have a decreased odds of timely urological evaluation after a referral for elevated PSA in our diverse patient population. Our study underscores cohorts that may benefit from implementation of institutional safeguards such as patient navigation systems to facilitate and ensure appropriate follow-up upon referral for elevated PSA.
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Neoplasias da Próstata , Urologia , Masculino , Humanos , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Estudos Retrospectivos , Encaminhamento e ConsultaRESUMO
The objective of this study is to evaluate the conventional dietary recommendations for stone prevention among patients in the National Health and Nutritional Examination Survey (NHANES) and compare dietary components and special diets between stone formers and non-stone formers. We analyzed the NHANES 2011-2018 dietary and kidney condition questionnaires, among 16,939 respondents who were included in this analysis. Dietary variables were selected based on the American Urological Association (AUA) guideline for Medical Management of Kidney Stones and from other studies on kidney stone prevention. Weighted multivariate logistic regression models were used to assess the relationship of dietary food components (categorized into quartiles) and dietary recommendations with kidney stone formation (yes vs no), adjusted for total caloric intake, comorbidities, age, race/ethnicity, and sex. The prevalence of kidney stones was 9.9%. Our results showed association of kidney stones with lower levels of potassium (p for trend = 0.047), which was strongest for < 2000 mg (OR = 1.35; 95% CI 1.01-1.79). Higher vitamin C intake was inversely associated with stone formation (p for trend = 0.012), particularly at daily intake levels between 60 and 110 mg (OR = 0.76; 95% CI 0.60-0.95) and above 110mcg (OR = 0.80; 95% CI 0.66-0.97). There were no associations between other dietary components and kidney stone formation. Higher levels of dietary vitamin C and potassium intake may be indicated for stone prevention and warrants further investigation.
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Dieta , Cálculos Renais , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Dieta/efeitos adversos , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Cálculos Renais/prevenção & controle , Vitaminas , Ácido AscórbicoRESUMO
OBJECTIVE: Fractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma. METHODS: A retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models. RESULTS: A higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (ß = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (ß = 16.1, 95% CI: 1.5 to 30.8). CONCLUSIONS: Intermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children.
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Obstrução das Vias Respiratórias , Asma , Humanos , Criança , Asma/diagnóstico , Asma/epidemiologia , Teste da Fração de Óxido Nítrico Exalado , Estudos Retrospectivos , Óxido Nítrico , Testes Respiratórios , Morbidade , Expiração , BiomarcadoresRESUMO
BACKGROUND: Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in individuals with human immunodeficiency virus (HIV) even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in adults with HIV with cryptococcal antigenemia is unknown. METHODS: Cryptococcal capsular glucuronoxylomannan (GXM)- and naturally occurring ß-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans with HIV who underwent CrAg screening and were followed up to 6 months. Associations between antibody titers, CrAg status, and all-cause mortality were sought using logistic and Cox regression, respectively. RESULTS: Compared with CrAg-negative individuals (n = 130), CrAg-positive individuals (n = 67) had significantly higher IgG1 (median, 6672; interquartile range [IQR], 4696-10 414 vs 5343, 3808-7722 µg/mL; P = .007), IgG2 (1467, 813-2607 vs 1036, 519-2012 µg/mL; P = .01), and GXM-IgG (1:170, 61-412 vs 1:117, 47-176; P = .0009) and lower curdlan-IgG (1:47, 11-133 vs 1:93, 40-206; P = .01) titers. GXM-IgG was associated directly with cryptococcal antigenemia adjusted for CD4 count and antiretroviral therapy use (odds ratio, 1.64; 95% confidence interval [CI], 1.21 to 2.22). Among CrAg-positive individuals, GXM-IgG was inversely associated with mortality at 6 months adjusted for CD4 count and tuberculosis (hazard ratio, 0.50; 95% CI, .33 to .77). CONCLUSIONS: The inverse association of GXM-IgG with mortality in CrAg-positive individuals suggests that GXM-IgG titer may have prognostic value in those individuals. Prospective longitudinal studies to investigate this hypothesis and identify mechanisms by which antibody may protect against mortality are warranted.
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Cryptococcus , Infecções por HIV , Meningite Criptocócica , Adulto , Humanos , Estudos Prospectivos , África do Sul , Infecções por HIV/complicações , Contagem de Linfócito CD4 , Antígenos de Fungos , Imunoglobulina G , HIV , Meningite Criptocócica/diagnósticoRESUMO
BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.
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Estudo de Associação Genômica Ampla , Neoplasias da Próstata , África Subsaariana/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias da Próstata/genética , Fatores de RiscoRESUMO
Metabolomics analysis of urine before and after overactive bladder (OAB) treatment may demonstrate a unique molecular profile, allowing predictions of responses to treatment. This feasibility study aimed to correlate changes in urinary metabolome with changes in OAB symptoms after intravesical onabotulinumtoxinA (BTX-A) injections for refractory OAB. Women 18 years or older with non-neurogenic refractory OAB were recruited to complete OAB-V8 questionnaires and submit urine samples before and after 100 units intravesical BTX-A injection. Samples were submitted to CE-TOFMS metabolomics profiling. Data were expressed as percent of change from pre-treatment and were correlated with OAB-V8 score improvement. Urinary metabolite changes in the OAB-V8 groups were compared using the Kruskal-Wallis test, and associations between metabolites and OAB-V8 scores were examined using quantile regression analysis. Of 61 urinary metabolites commonly detected before and after BTX-A, there was a statistically significant decrease in adenosine and an increase in N8-acetylspermidine and guanidinoacetic acid levels associated with OAB score improvement, suggesting that intravesical BTX-A injection modifies the urinary metabolome. These urinary metabolites could provide insight into OAB pathophysiology and help identify patients who would benefit most from chemodenervation.
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PURPOSE: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.
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Alphapapillomavirus , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Anticorpos Antivirais , Detecção Precoce de Câncer , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/epidemiologiaRESUMO
INTRODUCTION: Small renal masses (SRMs) are often incidentally diagnosed, and a large proportion are malignant. However, there is a paucity of data describing predictors of malignancy in minority patients with SRMs. Thus, our goal was to examine clinical risk factors associated with SRM malignant histology in patients undergoing partial nephrectomy (PN) a diverse, urban academic center. MATERIALS AND METHODS: Patients with a SRM undergoing PN at a single institution between 2010 to 2018 were reviewed. Demographic, clinical, and imaging characteristics were compared to pathology results. Logistic regression was used to examine associations between demographic/clinical variables for malignant and high-grade histology. RESULTS: In total, 331 patients who underwent PN for SRM were included. Of those, 264 (79.8%) had malignant histology while 67 (20.2%) had benign histology. The proportions of men and of current smokers were significantly higher among patients with malignant histology. In multivariate models, non-Hispanic Black (NHB) patients had increased odds of having malignant histology (OR 2.46, 95% CI: 1.01-5.99, P = .048) and current smokers (OR = 4.02; 95% CI 1.14-14.18, P = .031). Hispanic patients had a 3-fold increased risk of high-grade RCC (OR 3.06, 95% CI: 1.19-7.87, P = 0.02) compared to Non-Hispanic White patients. CONCLUSION: In our population, male sex, smoking, and NHB race/ethnicity was associated with an increased risk of malignancy in patients undergoing partial nephrectomy for SRM. Older age and Hispanic race/ethnicity were associated with high grade RCC. Our results suggest that urologists should exercise a higher level of vigilance in managing and treating SRM among NHB and Hispanic patients.