American Cohort Research Articles

Clinical, Endoscopic, and Histopathologic Gastrointestinal Disease in an American Cohort With Behçet's Disease.

Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD. Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent. Eighty-three patients were evaluated. The majority were female (83.1%) and white (75.9%). Mean age was 36 ± 14.8 years. GI symptoms were reported in 75% of cohort with nearly half of reporting abdominal pain (48.2%) and significant numbers reporting acid reflux, diarrhea, and nausea/vomiting. Esophagogastroduodenoscopy was performed in 37 patients; erythema and ulcers were the most common found abnormalities. Colonoscopy was performed in 32 patients with abnormalities including polyps, erythema, and ulcers. Endoscopy was normal in 27% of esophagogastroduodenoscopies and 47% of colonoscopies. Vascular congestion was demonstrated on the majority of random biopsies throughout the GI tract. Inflammation was not highly prevalent on random biopsies except in the stomach. Wireless capsule endoscopy was performed on 18 patients; ulcers and strictures were the most common abnormalities. GI symptoms were common in this cohort of American patients with BD. Endoscopic examination was often normal; however, histopathologic examination demonstrated vascular congestion throughout the GI tract.

In-hospital and Post-discharge Status in COVID-19 Patients With Acute Respiratory Failure Supported With Extracorporeal Membrane Oxygenation.

Few data from Latin American centers on clinical outcomes in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome who required extracorporeal membrane oxygenation (ECMO) are published. Moreover, clinical and functional status after hospital discharge remains poorly explored in these patients. We evaluated in-hospital outcomes of severe COVID-19 patients who received ECMO support in two Brazilian hospitals. In one-third of the survivors, post-acute COVID-19 syndrome (PACS), quality of life, anxiety, depression, and return to work were evaluated. Eighty-five patients were included and in-hospital mortality was 47%. Age >65 years (HR: 4.8; 95% confidence interval [CI]: 1.4-16.4), diabetes (HR: 6.0; 95% CI: 1.8-19.6), ECMO support duration (HR: 1.08; 95% CI: 1.05-1.12) and dialysis initiated after ECMO (HR: 3.4; 95% CI: 1.1-10.8) were independently associated with higher in-hospital mortality and mechanical ventilation (MV) duration before ECMO was not (HR: 1.18; 95% CI: 0.71-2.09). PACS-related symptoms were reported by two-thirds and half of patients at 30- and 90-days post-discharge, respectively. The median EQ-5D score was 0.85 (0.70-1.00) and 0.77 (0.66-1.00) at 30 and 90 days. Of the 15 responders, all previously working patients, except one, have returned to work at 90 days. In conclusion, in-hospital mortality in a large Latin American cohort was comparable to the Global extracorporeal life support organization registry.

Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

BackgroundOver the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure. ObjectivesThe authors aimed to explore whether ImP is associated with heart failure and mortality. MethodsImP serum measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates. ResultsImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01). ConclusionsThe gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.

Frequency of Known Genetic Variants for Parkinson’s Disease in the PD GENEration Study Cohort (S42.002)

Frequency of Known Genetic Variants for Parkinson’s Disease in the PD GENEration Study Cohort (S42.002)

Prenatal Cannabis Use and Offspring Autism-Related Behaviors: Examining Maternal Stress as a Moderator in a Black American Cohort

Prenatal cannabis use and maternal stress have been proposed as risk factors for autism spectrum disorder (ASD). Black mothers and mothers of lower socioeconomic status (SES) may be especially likely to experience high levels of stress. This study examined the impact of prenatal cannabis use and maternal stress (i.e., prenatal distress, racial discrimination, and lower SES) on child ASD-related behaviors in a sample of 172 Black mother-child pairs. We found that prenatal stress was significantly associated with ASD-related behaviors. Prenatal cannabis use did not predict ASD-related behaviors and did not interact with maternal stress to predict ASD-related behaviors. These findings replicate previous work on prenatal stress-ASD associations and add to the limited literature on prenatal cannabis-ASD associations in Black samples.

Adiposity, aldosterone and plasma renin activity among African Americans: The Jackson Heart Study

ObjectiveTo analyze associations between adiposity and the renin-angiotensin-aldosterone system (RAAS) in a large African American (AA) cohort. MethodsCross-sectional associations of adiposity (body mass index [BMI], waist circumference [WC], waist:height ratio, waist:hip ratio, leptin, adiponectin, leptin:adiponectin ratio [LAR], subcutaneous [SAT] and visceral adipose tissue [VAT], and liver attenuation [LA]) with aldosterone, plasma renin activity (renin), and aldosterone:renin ratio (ARR) were assessed in the Jackson Heart Study using adjusted linear regression models. ResultsA 1-SD higher BMI was associated with a 4.8 % higher aldosterone, 9.4 % higher renin, and 5.0 % lower ARR (all p < 0.05). Log-leptin had the largest magnitude of association with renin (30.2 % higher) and ARR (9.6 % lower), while the strongest association of aldosterone existed for log-LAR (15.3 % higher) (all 1-SD, p < 0.05). SAT was only associated with renin. VAT was associated with higher aldosterone, renin, and ARR. Liver fat was associated with aldosterone and renin, but not ARR. Associations of WC, BMI, and SAT with aldosterone were greater in men while the association with VAT was greater in women (p-interactions < 0.05). ConclusionMultiple measures of adiposity are associated with the RAAS in AAs. Further studies should examine the role of RAAS in obesity-driven cardiometabolic diseases.

The role of aldosterone and ideal cardiovascular health in incident cardiovascular disease: The Jackson heart study

BackgroundHigher levels of ideal cardiovascular health (ICH) are associated with lower levels of aldosterone and incidence of cardiovascular disease (CVD). However, the degree to which aldosterone mediates the association between ICH and CVD incidence has not been explored. Thus, we investigated the mediational role of aldosterone in the association of 5 components of ICH (cholesterol, body mass index (BMI), physical activity, diet and smoking) with incident CVD and the mediational role of blood pressure (BP) and glucose in the association of aldosterone with incident CVD in a cohort of African Americans (AA). MethodsThe Jackson Heart Study is a prospective cohort of AAs adults with data on CVD outcomes. Aldosterone, ICH metrics and baseline characteristics were collected at exam 1 (2000–2004). ICH score was developed by summing 5 ICH metrics (smoking, dietary intake, physical activity, BMI, and total cholesterol) and grouped into two categories (0–2 and ≥3 metrics). Incident CVD was defined as stroke, coronary heart disease, or heart failure. Cox proportional hazard regression models were used to model the association of categorical ICH score with incident CVD. The R Package Mediation was utilized to examine: 1) The mediational role of aldosterone in the association of ICH with incident CVD and 2) The mediational role of blood pressure and glucose in the association of aldosterone with incident CVD. ResultsAmong 3,274 individuals (mean age: 54±12.4 years, 65% female), there were 368 cases of incident CVD over a median of 12.7 years. The risk of incident CVD was 46% lower (HR: 0.54; 95%CI 0.36, 0.80) in those with ≥3 ICH metrics at baseline compared to 0–2. Aldosterone mediated 5.4% (p = 0.006) of the effect of ICH on incident CVD. A 1-unit increase in log-aldosterone was associated with a 38% higher risk of incident CVD (HR 1.38, 95%CI: 1.19, 1.61) with BP and glucose mediating 25.6% (p<0.001) and 4.8% (p = 0.048), respectively. ConclusionAldosterone partially mediates the association of ICH with incident CVD and both blood pressure and glucose partially mediate the association of aldosterone with incident CVD, emphasizing the potential importance of aldosterone and ICH in risk of CVD among AAs.

MP40-02 BASELINE PSA LEVELS IN MIDLIFE &amp; FUTURE DEVELOPMENT OF LETHAL PROSTATE CANCER: A DIVERSE NORTH AMERICAN COHORT ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP40-02 BASELINE PSA LEVELS IN MIDLIFE & FUTURE DEVELOPMENT OF LETHAL PROSTATE CANCER: A DIVERSE NORTH AMERICAN COHORT ANALYSIS Matthew Davis, Alexander Stephens, Chase Morrison, Sami Majdalany, Rafe Affas, Sohrab Arora, Nicholas Corsi, Ivan Rakic, Akshay Sood, Craig Rogers, and Firas Abdollah Matthew DavisMatthew Davis More articles by this author , Alexander StephensAlexander Stephens More articles by this author , Chase MorrisonChase Morrison More articles by this author , Sami MajdalanySami Majdalany More articles by this author , Rafe AffasRafe Affas More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Ivan RakicIvan Rakic More articles by this author , Akshay SoodAkshay Sood More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of our study was to examine prostate cancer (PCa) mortality based on midlife prostate-specific antigen (PSA) results in a racially diverse North American population. METHODS: Our cohort included all men aged 40-59 years, who received their first PSA through our health system between the years 1995 and 2019. Next, patients were divided into 4 categories based on age as follows: 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years. First PSA testing represented the main predictor of interest, and it was categorized based on median and 90th percentile for each age category. Fine-Gray regression was used to examine the impact of the value of PSA at first testing on the risk of developing lethal PCa (i.e. prostate cancer-specific mortality) after accounting for all confounders including race and comorbidity among others. Cancer-specific mortality and overall mortality were obtained by linking our database to the Michigan Vital Records registry. RESULTS: A total of 129,067 men met inclusion criteria during the study period, of which 82,084 (64%) were White, 30,883 (24%) were Black, and 16,100 (12%) were other race. Median and 90th percentile PSA were 0.7 and 2.0 ng/ml, respectively. For men aged 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years, median PSA was respectively 0.6, 0.7, 0.7, and 0.9 ng/ml, and the 90th percentile PSA was respectively 1.4, 1.6, 2.1, and 3.0 ng/ml. For the same age categories, the estimated rate (95% CI) of lethal PCa at 20 years was 0.023% (0.003-0.130%), 0.14% (0.071-0.25%), 0.33% (0.19-0.54%), 0.51% (0.34-0.75%) in men with PSA < median, and 0.79% (0.22-2.2%), 0.16% (1.04-2.45%), 2.5% (1.80-3.35%), 5.4% (4.28-6.76%) in men with PSA ≥90th percentile. Median (IQR) follow-up was 7.8 (3.2-15.0) years. On multivariable analysis, men with a PSA≥90th percentile had a 11.57 HR (95% CI: 8.71-15.35) times higher risk of developing lethal PCa, when compared to those with PSA<median at first testing. This HR (95% CI) was 11.03 (2.01-60.57), 13.96 (6.93-28.13), 13.01 (7.62-22.23), and 10.47 (7.09-15.47) for men aged 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years, respectively. CONCLUSIONS: Our findings suggest that midlife first-time PSA is an important predictor of the subsequent risk of developing lethal PCa. This information can be used to develop a PSA screening program, which is tailored to the patient’s specific risk. To the best of our knowledge, our report is the first to examine the role of first-time PSA in a diverse North American cohort. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e545 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Davis More articles by this author Alexander Stephens More articles by this author Chase Morrison More articles by this author Sami Majdalany More articles by this author Rafe Affas More articles by this author Sohrab Arora More articles by this author Nicholas Corsi More articles by this author Ivan Rakic More articles by this author Akshay Sood More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

MP77-04 RACIAL DISPARITIES IN FUTURE DEVELOPMENT OF LETHAL PROSTATE CANCER BASED ON PSA LEVELS IN MIDLIFE

You have accessJournal of UrologyCME1 Apr 2023MP77-04 RACIAL DISPARITIES IN FUTURE DEVELOPMENT OF LETHAL PROSTATE CANCER BASED ON PSA LEVELS IN MIDLIFE Matthew Davis, Alexander Stephens, Chase Morrison, Sami Majdalany, Rafe Affas, Sohrab Arora, Nicholas Corsi, Ivan Rakic, Akshay Sood, Craig Rogers, and Firas Abdollah Matthew DavisMatthew Davis More articles by this author , Alexander StephensAlexander Stephens More articles by this author , Chase MorrisonChase Morrison More articles by this author , Sami MajdalanySami Majdalany More articles by this author , Rafe AffasRafe Affas More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Ivan RakicIvan Rakic More articles by this author , Akshay SoodAkshay Sood More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous literature has examined prostate cancer (PCa) mortality in a Scandinavian population based on midlife PSA results. The aim of our study was to examine racial disparities in PCa mortality based on midlife PSA results in a North American population. METHODS: Our cohort included self-identified White and Black men aged 40-59 years, who received their first PSA through our health system between the years 1995 and 2019. Next, patients were divided into 4 categories based on age as follows: 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years. First PSA testing represented the main predictor of interest, and it was categorized based on median and 90th percentile for each age category. Fine-Gray regression was used to examine the impact of the value of PSA at first testing on the risk of developing lethal PCa (i.e. PCa-specific mortality) by race after accounting for all confounders including Charlson comorbidity index among others. Cancer-specific mortality and overall mortality were obtained by linking our database to the Michigan Vital Records registry. RESULTS: A total of 112,967 men met inclusion criteria, of whom 82,084 (73%) were White and 30,883 (27%) were Black. Median and 90th percentile PSA were 0.7 and 2.0 ng/ml, respectively, in White men compared to 0.7 and 2.1 ng/ml, respectively, in Black men. For White men aged 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years, median PSA was respectively 0.6, 0.7, 0.7, and 0.9 ng/ml compared to 0.6, 0.7, 0.8, and 0.9 ng/ml in Black men. The 90th percentile PSA in White men was respectively 1.3, 1.6, 2.0, and 2.8 ng/ml compared to 1.4, 1.8, 2.4, and 3.8 ng/ml in Black men. For the same age categories, the estimated rate of lethal PCa at 20 years was significantly higher in Black men when using the 90th percentile PSA cutoff (see Table 1). Median (IQR) follow-up was 6.7 (2.9 - 14.4) years for White men and 9.9 (4.4 - 16.4) years for Black men. On multivariable analysis, these findings were confirmed. CONCLUSIONS: Our findings suggest that Black men are significantly more likely to develop lethal PCa based on previously published midlife first-time PSA cutoffs. This information suggests that a lower midlife PSA cutoff could be considered amongst Black men. To the best of our knowledge, our report is the first to examine the racial disparities in lethal PCa based on first-time PSA results in a diverse North American cohort. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1102 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Davis More articles by this author Alexander Stephens More articles by this author Chase Morrison More articles by this author Sami Majdalany More articles by this author Rafe Affas More articles by this author Sohrab Arora More articles by this author Nicholas Corsi More articles by this author Ivan Rakic More articles by this author Akshay Sood More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

MP69-18 EVALUATING THE ROLE OF LYMPHVASCULAR INVASION AS AN INDICATOR FOR ADVERSE OUTCOMES IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AND ITS HISTOLOGICAL SUBTYPES

You have accessJournal of UrologyCME1 Apr 2023MP69-18 EVALUATING THE ROLE OF LYMPHVASCULAR INVASION AS AN INDICATOR FOR ADVERSE OUTCOMES IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AND ITS HISTOLOGICAL SUBTYPES Ivan Rakic, Matthew Davis, Nicholas Corsi, Alexander Stephens, Sohrab Arora, Nikola Rakic, Taylor Malchow, Chase Morrison, Rafe Affas, Akshay Sood, Craig Rogers, and Firas Abdollah Ivan RakicIvan Rakic More articles by this author , Matthew DavisMatthew Davis More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Alexander StephensAlexander Stephens More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Nikola RakicNikola Rakic More articles by this author , Taylor MalchowTaylor Malchow More articles by this author , Chase MorrisonChase Morrison More articles by this author , Rafe AffasRafe Affas More articles by this author , Akshay SoodAkshay Sood More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymphvascular invasion (LVI) is recognized as an adverse prognostic factor in many cancers. However, its utility in upper tract urothelial carcinoma (UTUC) has not been well-defined. Our aim is to assess the prognostic ability of LVI in UTUC urothelial carcinoma (UC) and micropapillary urothelial carcinoma (MPUC) subtypes as a predictor of overall survival (OS) using a large North American cohort. METHODS: Our cohort included 9750 cM0 UTUC patients who underwent a radical nephroureterectomy (RNU), between 2004 and 2015, within the National Cancer Database (NCDB). The main variable of interest was LVI status, and its interaction with pathological nodal (pN) status. Kaplan-Meier curves were used to estimate the OS. Cox regression analysis tested the impact of LVI status on OS after accounting for covariates: age, sex, race, year of diagnosis, Charlson Comorbidity Index, income, treatment center type, insurance status, pathological tumor, and pN status. RESULTS: Mean (SD) age was 70.90±10.9 years. Overall, 14.4% had LVI, and 6.77% had pN+ (pN1-3) disease. The rate of advanced stage (pT3 or higher), and pN+ disease was 78.8%% and 18.1% in patients with LVI vs. 34.7% and 3.32% in patients without LVI. The histological subtypes were UC, pure squamous, sacromatoid/spindle cell carcinoma, and MPUC in respectively 49.8%, 0.608%, 0.708%, and 48.9% of patients. The mean (SD) follow-up was 42.9±35.3 months. In patients with UC at 5-years post-RNU, the OS rates were 60.2%, 29.9%, 28.9%, and 20.8% in patient with pN0 without LVI, pN0 with LVI, pN+ without LVI, and pN+ with LVI, respectively (p<0.001). In patients with MPUC at 5-years post-RNU, the OS rates were 65.3%, 40.2%, 54.7%, and 36.5% in patient with pN0 without LVI, pN0 with LVI, pN+ without LVI, and pN+ with LVI, respectively (p<0.001). On multivariable analysis, LVI was an independent predictor of less favorable OS outcomes, as those with LVI had a 1.82-fold higher risk of death (95% CI: 1.21-1.54, p<0.001), when compared to their counterpart without LVI. CONCLUSIONS: To the best of our knowledge, our report is the first to examine the impact of LVI on OS in a large North American nationwide cohort. Our results indicate that LVI is associated with less favorable survival outcomes in patient with UTUC who are treated surgically, and can be utilized for counseling after RNU and as a risk-stratification tool for future clinical trials. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e972 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ivan Rakic More articles by this author Matthew Davis More articles by this author Nicholas Corsi More articles by this author Alexander Stephens More articles by this author Sohrab Arora More articles by this author Nikola Rakic More articles by this author Taylor Malchow More articles by this author Chase Morrison More articles by this author Rafe Affas More articles by this author Akshay Sood More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

THE PRECIOUS STUDY: A PROSPECTIVE, OBSERVATIONAL STUDY OF CD8+ BIOMARKER BASED PROGNOSTIC TEST IN NORTH AMERICAN IBD PATIENTS

The clinical course of IBD varies considerably among patients1. One barrier to personalized medicine in IBD is the lack of a reliable prognostic assay that can be used at diagnosis to guide effective therapy for each patient, to optimize clinical outcomes and minimize complications. To address this need, a whole-blood qPCR-based prognostic assay was developed to divide IBD patients into two subgroups2. This transcriptional signature yields CD8 T-cell exhaustion level data that correlated with disease outcomes among IBD patients in UK2. Here, we aimed to determine if this prognostic assay could stratify an ethnically diverse North American cohort of IBD patients at diagnosis into low and high-risk subgroups.

Strong Positive Selection in Aedes aegypti and the Rapid Evolution of Insecticide Resistance.

Aedes aegypti vectors the pathogens that cause dengue, yellow fever, Zika virus, and chikungunya and is a serious threat to public health in tropical regions. Decades of work has illuminated many aspects of Ae. aegypti's biology and global population structure and has identified insecticide resistance genes; however, the size and repetitive nature of the Ae. aegypti genome have limited our ability to detect positive selection in this mosquito. Combining new whole genome sequences from Colombia with publicly available data from Africa and the Americas, we identify multiple strong candidate selective sweeps in Ae. aegypti, many of which overlap genes linked to or implicated in insecticide resistance. We examine the voltage-gated sodium channel gene in three American cohorts and find evidence for successive selective sweeps in Colombia. The most recent sweep encompasses an intermediate-frequency haplotype containing four candidate insecticide resistance mutations that are in near-perfect linkage disequilibrium with one another in the Colombian sample. We hypothesize that this haplotype may continue to rapidly increase in frequency and perhaps spread geographically in the coming years. These results extend our knowledge of how insecticide resistance has evolved in this species and add to a growing body of evidence suggesting that Ae. aegypti has an extensive genomic capacity to rapidly adapt to insecticide-based vector control.

Machine learning for predicting the survival in osteosarcoma patients: Analysis based on American and Hebei Province cohort.

Osteosarcoma, a rare malignant tumor, has a poor prognosis. This study aimed to find the best prognostic model for osteosarcoma. There were 2912 patients included from the SEER database and 225 patients from Hebei Province. Patients from the SEER database (2008-2015) were included in the development dataset. Patients from the SEER database (2004-2007) and Hebei Province cohort were included in the external test datasets. The Cox model and three tree-based machine learning algorithms (survival tree [ST], random survival forest [RSF] and gradient boosting machine [GBM]) were used to develop the prognostic models by 10-fold cross-validation with 200 iterations. Additionally, performance of models in the multivariable group was compared with the TNM group. The 3-year and 5-year cancer specific survival (CSS) were 72.71% and 65.92% in the development dataset, respectively. The predictive ability in the multivariable group was superior to that in the TNM group. The calibration curves and consistency in the multivariable group were superior to those in the TNM group. The Cox and RSF models performed better than the ST and GBM models. A nomogram was constructed to predict the 3-year and 5-year CSS of osteosarcoma patients. The RSF model can be used as a nonparametric alternative to the Cox model. The constructed nomogram based on the Cox model can provide reference for clinicians to formulate specific therapeutic decisions both in America and China.

Establishing an Approach for Designation of Evolving and Emerging Drug Threats.

Establishing an Approach for Designation of Evolving and Emerging Drug Threats.

Distribution of a novel CYP2C haplotype in Native American populations.

The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1KG superpopulations (range: 0.014-to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype.

Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. Factors associated with time to severe AIHA (hemoglobin level ≤7g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

A Protected Class, An Unprotected Condition, and A Biomarker - A Method/Formula for Increased Diversity in Clinical Trials for the African American Subject with Benign Ethnic Neutropenia (BEN).

Expanding on previous industry guidance relative to increased clinical trial diversity, while honing more exacting treatments and better ways to fight diseases that have often disproportionately impacted people of color, is a topic being discussed by multidisciplinary public health experts across the nation.This writing draws attention to the African American demographic, which is continually subject to health care disparities. Any glimpses of knowledge or medical discovery that could potentially help to redress harm or reinforce a weakened familial-cultural infrastructure should be emphasized for sanative restoration of the impacted communities. The focus of this writing is the African American cohort and its nexus to Benign Ethnic Neutropenia as the diverse target population of discussion, hoping to convey a harmonized approach in the examination of (1) the African American Benign Ethnic Neutropenia cohort within the context of basic scientific understanding, (2) the interplay of applicable governing regulatory protections, and (3) increased clinical trial participation to enlarge the pathway for increased diversity in clinical trials.

Risk factors for structural and functional progression of primary open-angle glaucoma in an African ancestry cohort

Background/aimsTo investigate the rates of structural and functional progression of primary open-angle glaucoma in an African ancestry cohort and identify risk factors for progression.MethodsThis retrospective study included 1424 eyes from...

Abstract Number ‐ 163: Underlying ICAD is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy

Introduction Acute large vessel occlusion (LVO) can be secondary to thromboembolism or intracranial atherosclerotic disease (ICAD). Data on LVO management due to underlying ICAD are scarce. We hypothesized that patients with ICAD have worse clinical outcomes following mechanical thrombectomy (MT) than those without ICAD. Methods We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center between January 14, 2018 and October 24, 2021. Presence of ICAD at LVO site was determined by the interventionalist. We compared in‐hospital mortality, 90‐day mortality, and 90‐day modified Rankin Scale (mRS) scores between those with and without ICAD, in unadjusted and adjusting logistic regression models. Results Among 215 patients (mean age 67.1±16.0 years; 60.5% female; 80.5% Black, median NIHSS score 16), ICAD was present in 38 patients (17.7%). Diabetes and dyslipidemia were more common in those with ICAD (57.9% vs. 38.4%, p = 0.027 and 29.0% vs. 14.7%, p = 0.035, respectively). Substantial reperfusion (TICI ≥ 2b) was achieved less often (84.2% vs. 94.4%, p = 0.031) but symptomatic ICH was also less common in ICAD patients (0% vs. 9.0%, p = 0.054). In‐hospital and 90‐day mortality were more common (36.8% vs. 15.8%, p = 0.003 and 52.6% vs. 26.6%, p = 0.002, respectively) and favorable functional outcome (mRS 0–2) at 90 days was less common (7.9% vs. 33.9%, p = 0.001) in ICAD patients. After adjusting for prognostic variables, ICAD was independently associated with in‐hospital mortality (OR = 4.1, 95% CI 1.7‐9.7), 90‐day mortality (OR = 3.7, 95% CI 1.6‐8.6), and poor functional outcome at 90 days (OR = 5.5, 95% CI 1.6‐19.4). Conclusions Symptomatic ICAD in a predominantly African American cohort is associated with increased odds of mortality and poor functional outcome at 90 days in patients with LVO undergoing MT. Further research is warranted to understand factors associated with worse outcomes and investigate alternative interventional approaches and medical management in this high‐risk population.

Unintended Bias in Artificial Intelligence Driven Diagnosis of Melanoma: A Systematic Review

Melanoma remains a public health crisis, with incidence rates increasing rapidly in the past decades. Improving diagnostic accuracy to decrease misdiagnosis using Artificial intelligence (AI) continues to be documented. Unfortunately, unintended racially biased outcomes a product of lack of diversity in the dataset used, with a noted class imbalance favoring lighter vs. darker skin tone have increasingly been recognized as a problem. Resulting in noted limitations of the accuracy of the Convolutional neural network (CNN) models. CNN models are prone to biased output due to biases in the dataset used to train them. Although the incidence of melanoma is lower in patients with darker skin tone, it is associated with a worse prognosis than in Caucasians, underscoring the need for accurate early diagnosis in these patients. Our objective in this systematic review was to assess to what degree race/ethnicity, specifically Black/ African American patient cohort were included in training datasets used in generating machine learning algorithms for automated melanoma diagnosis. Our review documents the fact that there is a remarkable lack of and inconsistent reporting of patient demographics especially race/ethnicity with notable under-representation of patients of color, highlighting a currently unmet critical need of lack of diversity in the publicly available skin image datasets. These publicly available skin image datasets, are an inherently unbalanced unintentionally biased datasets from which AI models created for the diagnosis of melanoma skin cancer have restricted applicability to real life clinical scenarios and limited population representation preventing generalizability to the community as a whole.