Abstract Purpose Many dietary factors have either proinflammatory or anti-inflammatory properties. We previously developed a dietary inflammatory index (DII) to assess the inflammatory potential of ...diet. In this study, we conducted a construct validation of the DII based on data from a food frequency questionnaire and three inflammatory biomarkers in a subsample of 2567 postmenopausal women in the Women's Health Initiative Observational Study. Methods We used multiple linear and logistic regression models, controlling for potential confounders, to test whether baseline DII predicted concentrations of interleukin-6, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha receptor 2, or an overall biomarker score combining all three inflammatory biomarkers. Results The DII was associated with the four biomarkers with beta estimates (95% confidence interval) comparing the highest with lowest DII quintiles as follows: interleukin-6: 1.26 (1.15–1.38), Ptrend < .0001; tumor necrosis factor alpha receptor 2: 81.43 (19.15–143.71), Ptrend = .004; dichotomized hs-CRP (odds ratio for higher vs. lower hs-CRP): 1.30 (0.97–1.67), Ptrend = .34; and the combined inflammatory biomarker score: 0.26 (0.12–0.40), Ptrend = .0001. Conclusions The DII was significantly associated with inflammatory biomarkers. Construct validity of the DII indicates its utility for assessing the inflammatory potential of diet and for expanding its use to include associations with common chronic diseases in future studies.
To determine whether patients with ureteral stones received different standard of care in the emergency department (ED) according to various sociodemographic factors. We conducted a retrospective ...study of patients presenting to EDs in a large tertiary-care hospital in the Bronx, New York with a diagnosis of ureteral stones. Electronic chart review was used to assess each patient’s ED course and to gather socio-demographic information. The primary outcomes of interest were administration of pain medication, prescription of alpha-1 antagonists to facilitate stone passage, and whether or not patients received CT scan or ultrasound. Associations of these outcomes with age categories, sex, race/ethnicity, BMI category, socioeconomic status and insurance status were examined using multivariate logistic regression models. 1200 patients were included in this analysis of which 616 (51%) were women. A large proportion of patients were minorities: 40% Hispanic, 15% non-Hispanic Black, and 20% other/multiracial. Patients aged 55–64 years and those 65 or older were less likely to receive pain medication compared to patients < 35 years (OR = 0.48, 95% CI 0.27–0.86,
p
= 0.01 and OR = 0.46, 95% CI 0.21–1.00,
p
= 0.05, respectively). Women were less likely than men to undergo any form of diagnostic imaging (OR = 0.52, 95% CI 0.35–0.76,
p
= 0.001). Similarly, patients in the lowest quintile of SES received less imaging than patients in the highest SES group (OR = 0.50, 95% CI 0.27–0.90,
p
= 0.02). Finally, women were less likely to receive alpha blockade compared to men (OR = 0.68, 95% CI 0.49–0.92,
p
= 0.014). Multiple disparities exist among patients presenting to the emergency department for ureteral stones.
Competing risk analyses have been widely used for the analysis of in-hospital mortality in which hospital discharge is considered as a competing event. The competing risk model assumes that more than ...one cause of failure is possible, but there is only one outcome of interest and all others serve as competing events. However, hospital discharge and in-hospital death are two outcomes resulting from the same disease process and patients whose disease conditions were stabilized so that inpatient care was no longer needed were discharged. We therefore propose to use cure models, in which hospital discharge is treated as an observed “cure” of the disease. We consider both the mixture cure model and the promotion time cure model and extend the models to allow cure status to be known for those who were discharged from the hospital. An EM algorithm is developed for the mixture cure model. We also show that the competing risk model, which treats hospital discharge as a competing event, is equivalent to a promotion time cure model. Both cure models were examined in simulation studies and were applied to a recent cohort of COVID-19 in-hospital patients with diabetes. The promotion time model shows that statin use improved the overall survival; the mixture cure model shows that while statin use reduced the in-hospital mortality rate among the susceptible, it improved the cure probability only for older but not younger patients. Both cure models show that treatment was more beneficial among older patients.
The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the "Percentage ...Method", defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark's Completeness Index (CCI) also have limitations.
We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset.
Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%).
The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high.
The trillions of microbes that colonize our adult intestine are referred to as the gut microbiome (GMB). Functionally it behaves as a metabolic organ that communicates with, and complements, our own ...human metabolic apparatus. While the relationship between the GMB and kidney stone disease (KSD) has not been investigated, dysbiosis of the GMB has been associated with diabetes, obesity and cardiovascular disease. In this pilot study we sought to identify unique changes in the GMB of kidney stone patients compared to patients without KSD. With an IRB-approved protocol we enrolled 29 patients into our pilot study. 23 patients were kidney stone formers and six were non-stone forming controls. Specimens were collected after a 6h fast and were flash frozen in dry ice and then stored at −80 °C. Microbiome: determination of bacterial abundance was by analysis of 16 s rRNA marker gene sequences using next generation sequencing. Sequencing of the GMB identified 178 bacterial genera. The five most abundant enterotypes within each group made up to greater than 50 % of the bacterial abundance identified. Bacteroides was 3.4 times more abundant in the KSD group as compared to control (34.9 vs 10.2 %;
p
= 0.001). Prevotella was 2.8 times more abundant in the control group as compared to the KSD group (34.7 vs 12.3 %;
p
= 0.005). In a multivariate analysis including age, gender, BMI, and DM, kidney stone disease remained an increased risk for high prevalence for Bacteroides (OR = 3.26,
p
= 0.033), whereas there was an inverse association with Prevotella (OR = 0.37,
p
= 0.043). There were no statistically significant differences in bacterial abundance levels for Bacteroides or Prevotella when comparing patients with and without DM, obesity (BMI >30), HTN or HLD. 11 kidney stone patients completed 24 h urine analysis at the time of this writing. Looking at the bacterial genuses with at least 4 % abundance in the kidney stone group, Eubacterium was inversely correlated with oxalate levels (
r
= −0.60,
p
< 0.06) and Escherichia trended to an inverse correlation with citrate (
r
= −0.56,
p
< 0.08). We also compared bacterial abundance between uric acid (UA) stone formers (
n
= 5) and non UA stone formers (
n
= 18) and found no significant difference between them. We identified two genus of bacteria in the GMB that had significant association with KSD. Interestingly, components of the 24-h urine appear to be correlated to bacterial abundance. These preliminary studies for the first time associate differences in the GMB with kidney stone formation. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in kidney stone disease.
Several studies have reported associations between vascular calcifications and urinary stone disease (USD). However, results have been inconsistent and the majority of studies did not report on ...race/ethnicity. We examined the association between vascular calcifications and USD in a large, racially/ethnically diverse patient population. We identified 672 USD cases and 672 controls (i.e., patients without a history of USD) from patients who underwent non-contrast CT imaging at Montefiore Medical Center in Bronx, New York between 2004 and 2013. Controls were matched to cases on age, sex and race/ethnicity. The non-contrast CT imaging was used to measure abdominal aortic calcification (AAC) and calculate the AAC severity score. Logistic regression models were used to examine associations of AAC presence and severity score with risks of USD and stone types. Cases and controls had similar AAC prevalence (45.2% vs. 44.8%,
p
= 0.87), and AAC severity score (median 10 vs. 9.3,
p
= 0.47). The presence of AAC (OR = 0.98, 95% CI 0.78–1.23;
p
= 0.86) or AAC severity score were not associated with risk of USD: ORs of 0.96, 0.87, 1.07 and 1.03 for increasing AAC quartiles (
p
-trend = 0.54). There were also no associations in the stratified analyses by race/ethnicity or by sex. However, when USD patients were stratified by stone type, brushite/apatite stone formers had an inverse association with the lowest quartile of AAC severity score (OR = 0.35, 95% CI 0.11–0.84,
p
= 0.04) in comparison to patients without AAC. Overall, we found no association between vascular calcifications and risk of urinary stone disease in this large, hospital-based, case–control study.
Purpose: Protein-truncating mutations in BRCA1 and in particular BRCA2 genes have been associated with prostate cancer. However, there is still uncertainty about the magnitude of association ...particularly
with Gleason score, and family history of prostate, breast, and ovary cancers.
Experimental Design: To further examine associations between three founder mutations located in BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) genes and prostate cancer, we conducted a study of 979 prostate cancer cases and 1,251 controls among Ashkenazi
Jewish men. Detailed information was obtained on prostate cancer pathology, age at diagnosis, and family history of all cancers.
Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression models.
Results: Prostate cancer risk was increased (OR, 1.9; 95% CI 0.9-4.1) for BRCA2 mutation carriers but not for BRCA1 mutation carriers. BRCA2 mutation carriers had an OR of 3.2 (95% CI, 1.4-7.3) for Gleason score of 7 to 10, but no association was observed for Gleason
score of <7. Carriers of BRCA1- 185delAG mutation also had an OR of 3.5 (95% CI, 1.2-10.3) for Gleason score of ≥7 tumors; however, the association of either
BRCA1 -185delAG or 5382insC mutation was not statistically significant. Associations between founder mutations and prostate cancer
were stronger in men with no first-degree family history of breast and/or ovarian cancers but were unaffected by family history
of prostate cancer.
Conclusion: These results indicate that the BRCA2 founder mutation confers a 3-fold elevated risk of high-grade prostate cancer. Although BRCA1 mutations were not associated with prostate cancer, the BRCA1 -185delAG was associated with high Gleason score tumors. These findings should be carefully considered in genetic counseling
and/or evaluating therapeutic options.
The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide ...significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P=9 × 10(-18)), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21-0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49-0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations.
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.
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.
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.
Objective
To perform a systematic review and a retrospective cohort analysis evaluating the rates of surgical downgrading of prostate cancer (PCa) from biopsy (PBx) to radical prostatectomy (RP), and ...their association with biochemical recurrence (BCR) in a multiethnic population.
Methods
A systematic review of PubMed and other databases was performed. We included retrospective studies evaluating the relationship between surgical downgrading and BCR-free survival. Data regarding Gleason score (GL) downgrading were abstracted from the articles and categorized as follows: GL8-10 to GL7, GL7 to GL6, and GL 7(4 + 3) to GL7(3 + 4). We also performed a retrospective cohort review of patients who underwent RP at our institution from 2005 through 2020. Kaplan–Meier survival analysis and Cox proportional hazards models were used to compare BCR among downgraded versus non-downgraded men.
Results
Systematic review yielded 137 abstracts; of these, 36 full-texts were reviewed, 8 of which were included in our systematic review. Despite substantial variability, all showed that GL at RP is one of the most important factors of BCR-free survival. A total of 1,484 men with PCa were analyzed from our institution. On multivariate analysis, GL7 to GL6 downgrading (HR = 0.50,
p
= 0.022) and GL8-10 to GL7 downgrading (HR = 0.42,
p
= 0.011) were associated with reduced risk of BCR when compared to men with GL7 and GL8-10 concordance, respectively. However, GL7(4 + 3) to GL7(3 + 4) downgrading was not significantly associated with reduced BCR (HR = 0.56,
p
= 0.12), when compared to GL7(4 + 3) concordance, although HR was similar.
Conclusion
Surgical downgrading at RP was associated with a reduced risk of BCR compared to GL concordant disease, and these findings have been validated within our multiethnic population. Pathologic downgrading at the time of RP may be a more useful predictor of subsequent BCR in comparison to that associated with GL concordant pathology.
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