Afro-Caribbean Ethnicity Research Articles

Exploring the potential link between prostate cancer and magnetic fields

Prostate cancer is the most common solid cancer in men worldwide. Various lifestyle factors have been established as contributors to cancer risk, and prostate cancer is no exception. Elements such as advanced age, diet, obesity, smoking, alcohol consumption, circadian rhythm disruptions, Afro-Caribbean ethnicity, and sexual activity have all been linked to an increased risk of prostate cancer. Notably, famous male guitarists from bands spanning the last few decades are now entering the age demographic most closely associated with prostate cancer. It is not surprising that they may fall into the ’at-risk’ category. Media speculation has hinted at a potentially higher incidence of prostate cancer among guitarists compared to their bandmates, although no tangible correlation has been established. This speculation piqued our curiosity and prompted an exploration into potential reasons why musicians, particularly guitarists, might be at an elevated risk of developing prostate cancer. We hypothesise the electromagnetic fields generated by the electric guitar may in part explain the possible increase in prostate cancer risk among electric guitarists. This study delves into these intriguing possibilities, shedding light on an area of research that remains speculative but warrants further investigation.

Switching Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide Fumarate (TAF) in Hepatitis B/HIV Co-Infection: A Feasibility Study

PurposeTenofovir alafenamide (TAF) delivers the active metabolite more efficiently to target cells compared with tenofovir disoproxil fumarate (TDF). Recent studies suggest that TAF is efficacious in treatment naïve individuals who are co-infected with HBV/HIV and may have superior effects on HBV e antigen (HBeAg) seroconversion in this setting. The primary objective of this study was to explore the feasibility of switching from TDF to TAF in HBV/HIV co-infection. MethodsIn this single-arm, multicenter, open-label study, we recruited patients (n = 20) who were on stable TDF-based antiviral therapy for at least 12 months. All participants had undetectable HIV RNA and HBV DNA levels at the time of screening and were converted to a TAF-based treatment regimen (TAF + emtricitabine + third agent) for 48 weeks. FindingsTwenty-seven individuals were invited to take part in the screening process; 3 met the exclusion criteria and a further 4 withdrew consent prior to enrolment. The remaining participants were predominantly male (70%), non-cirrhotic (95%) and of Afro-Caribbean ethnicity (60%). All were co-infected with HIV-1 and established on long-term antiretroviral treatment prior to enrolment (median 6.5 years). No adverse events related to the study drug were observed, and most patients (89.5%) maintained undetectable HIV RNA and HBV DNA throughout the follow-up period. ImplicationsSwitching from TDF to TAF in HBV/HIV co-infection was safe, well tolerated and maintained virological suppression in most patients. Additional studies are needed to confirm these findings in larger cohorts and explore other endpoints.

Prevalence, characteristics and outcomes of older patients with hereditary versus wild-type transthyretin amyloid cardiomyopathy.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is often assumed to be associated with wild-type TTR genotype (ATTRwt) in elderly patients (aged ≥70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of transthyretin (TTR) variants among elderly patients diagnosed with ATTR-CM. Data from consecutive patients over 70 years of age diagnosed with ATTR-CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all-cause mortality. The study population consisted of 2029 patients with ATTR-CM (median age 79 years at diagnosis, 13.5% females, 80.4% Caucasian). Variant ATTR-CM (ATTRv-CM) was diagnosed in 20.7% (n=421) of the study population of whom 327 (77.7%) carried V122I, 47 (11.2%) T60A, 16 (3.8%) V30M and 31 (7.3%) other pathogenic TTR variants. During a median (range) follow-up of 29 (12-48) months, ATTRv-CM was associated with increased all-cause mortality compared to ATTRwt-CM, with the poorest survival observed in V122I-associated ATTRv-CM (p < 0.001). Univariable and multivariable logistic regression analyses in those with ATTR-CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p < 0.001), female sex (OR 2.73, p < 0.001), Afro-Caribbean ethnicity (OR 65.5, p < 0.001), atrial fibrillation (OR 0.65, p=0.015), ischaemic heart disease (OR 0.54, p=0.007), peripheral polyneuropathy (OR 5.70, p < 0.001) and orthostatic hypotension (OR 6.29, p < 0.001) to be independently associated with ATTRv-CM. Up to 20.7% of elderly patients with ATTR-CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR-CM regardless of age.

189 PREVALENCE, DISEASE CHARACTERISTICS AND OUTCOMES OF HEREDITARY TRANSTHYRETIN AMYLOID CARDIOMYOPATHY AMONG ELDERLY INDIVIDUALS

Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR-CM) is often assumed to be associated with wild-type TTR genotype (ATTRwt) in elderly patients (aged ≥70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of variant ATTR-CM (ATTRv-CM) among elderly patients. Methods Data from consecutive patients over 70 years of age diagnosed with ATTR-CM at the UK National Amyloidosis Centre between January 2012 and June 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all-cause mortality. Results The study population consisted of 2164 patients with ATTR-CM (median age 79 years at diagnosis, 13.2% females, 80.4% Caucasian). ATTRv-CM was diagnosed in 20% (n=431) of the study population of whom 329 (76.3%) carried V122I, 49 (11.4%) T60A, 18 (4.2%) V30M and 35 (8.1%) other pathogenic TTR variants. During a median (range) follow up of 29 (12-48) months, ATTRv-CM was associated with increased all-cause mortality compared to ATTRwt-CM, with the poorest survival observed in V122I-associated ATTRv-CM (p&amp;lt;0.001). Univariable and multivariable binary logistic regression analyses in those with ATTR-CM showed younger age at diagnosis (odds ratio [OR] 0.86 per year, p&amp;lt;0.001), female sex (OR 3.0, p&amp;lt;0.001), Afro-Caribbean ethnicity (OR 59.1, p&amp;lt;0.001), atrial fibrillation (OR 0.65, p=0.015), ischemic heart disease (OR 0.54, p=0.007), peripheral polyneuropathy (OR 3.72, p&amp;lt;0.001) and orthostatic hypotension (OR 3.75, p=0.001) to be independently associated with ATTRv-CM. Conclusions Up to 20% of elderly patients with ATTR-CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR-CM regardless of age.

314.10: Controlling the Cytokine Stom With Therapeutic Plasma Exchange: The MTI Experience With Solid Organ Transplant Recipients

Introduction: The solid organ transplant recipient (SOTr) have suffered a tremendous impact from coronavirus pandemic. The use of immunosuppressants and frequent associated medical comorbidities put this population at extreme risk for developing SARS-CoV-2 associated pneumonia. SARS-CoV-2-related mortality is higher in SOTr. It has been hypothesized that cytokine release storm (CRS) is the leading cause of ARDS in COVID-19 and timely control of this inflammatory response may improve outcomes. We report our experience of using therapeutic plasma exchange (TPE) to improve outcomes by tackling CRS in a timely manner. Methods: This is a single-center, retrospective cohort study of SOTr diagnosed with SARS-CoV-2 infection from April 2020 to April 2021. All the patients received severity stratified institutional protocolized treatment and TPE was initiated based on clinical and inflammatory parameters of CRS and ARDS. TPE patients received Methylprednisolone 250 mg x 3 days then 125 mg x 2 days, followed by Prednisone 60 mg x 2 days and then 30 mg x 2 days. All patients received prophylaxis with omeprazole, ivermectin 0.2 mg/Kg daily for 2 days followed by 2 additional doses 2 weeks later, and trimethoprim/sulfamethoxazole (renally adjusted) 3 times weekly for 3 months. Laboratory markers, immunosuppression, WHO severity score pre- and post-TPE therapy and outcomes including mortality were analyzed. For risk factor analysis for mortality, we performed logistic regression analysis for univariate analysis. After that, based on the univariate analysis, we developed multivariate model. We conducted multiple logistic regression analysis with stepwise backward elimination. Results: 62 patients were followed for median of 141 days (range 8-376). The median age was 60 years (range 28-78), 65% were male, 76% had hypertension, 55% had diabetes and 81% were overweight with a BMI > 25 kg/m2. 90% were of Hispanics and Afro-Caribbean ethnicity. The most common transplanted organ was kidney with 54 patients (87%), followed by liver with 4 patients (6.5%). Time from transplant to diagnosis was 10 months(median, IQR 4-37) and time from symptoms to admission was 3 days (median, IQR 2-5). 79% of the patients were admitted to an intensive care unit (ICU). Tacrolimus (77%) and mycophenolate mofetil (87%) were the most common immunosuppressant drugs used with mycophenolate mofetil being held in 75% of the patients. The median of TPE sessions was 5 (range 1-20). Prior to TPE, there were 27 patients (44%) requiring ventilatory support and additional support (vasopressors, Renal Replacement Therapy (RRT) or Extracorporeal Membrane Oxygenation (ECMO)). A reduction of 32% support on the 27 patients was observed after TPE. The WHO severity score pre- and post-TPE therapy was statistically significant (p<0.001). The overall mortality was 26/62 patients (42%). Secondary infections were diagnosed in 35/62 (56%) of patients with 77 % leading to mortality and of those, 38 % were fungal infections. The median length of stay was 42 days (range 2-207). 4/54 (7%) kidney transplant recipients developed graft failure at 9, 18, 139 and 344 days respectively; and 4/54 (7%) had episodes of acute rejections at 1,14, 22 and 124 days of COVID diagnosis, respectively. Univariable analysis showed that older age and elevated LDH pre TPE and the lack of decline on LDH, D Dimer, CRP and ferritin values post TPE were risk factors for mortality (p=0.001; 0.022; 0.006; 0.004; 0.0002 and 0.043, respectively). The presence of a secondary infection was correlated with increased likelihood of death from 25% to 55% and it occurred with a mean of 8 days (range 1-65) from its diagnosis. Multivariate analysis showed older age and CRP values post TPE as risk factors for mortality (p=0.015 and 0.04, respectively). Conclusion: SARS-CoV-2 infection with cytokine storm leading to ARDS leads to high mortality, especially in the SOTr. TPE appears to be a valuable tool to control the cytokine storm by reducing the systemic inflammatory response and improving the overall critical state. Alongside with older age, we observed that high levels of LDH pre TPE and the persistent high levels of the other inflammatory parameters, specifically CRP post TPE and secondary infections, were predictors of mortality. Further research is needed to establish if these findings can lead to clinical guidelines.

Recurrence of Primary and Secondary Keloids in a Select African American and Afro-Caribbean Population.

Keloid formation occurs with increased incidence in African Americans and Afro-Caribbeans when compared with other ethnic populations. Although surgical management and nonsurgical management of keloids are mainstays of treatment, there are significant variations within studies comparing the efficacy of intraoperative steroid injection, postoperative radiotherapy, or a combination of both modalities. The purpose of our study is to evaluate the efficacy of different treatment modalities used for treatment of keloids and to determine their recurrence in a select Afro-Caribbean population. A retrospective review of the plastic surgery case list from January 2015 to October 2019 was conducted, with identification of 46 Afro-Caribbean and African American patients with 56 keloids. Each patient was contacted to determine whether they had experienced recurrence of their keloid(s). Eighteen patients were lost to follow-up, resulting in 28 patients with 35 keloids included in our study. The treatment protocol involved surgical excision for all keloids, with selective additional triamcinolone 40 mg/mL injection intraoperatively, immediate postoperative radiotherapy, or intraoperative triamcinolone injection with postoperative radiotherapy. Recurrence rates between the different treatment groups were calculated, and statistical analyses were performed using IBM SPSS Statistics, with a value of P < 0.05 deeming statistical significance. Our study demonstrates that postoperative recurrence rates of primary and secondary keloids were 43% and 58%, respectively. Results of recurrence rate varied by specific treatment modality; keloid excision yielded a rate of only 54%, keloid excision with postoperative radiation yielded a rate of 83%, keloid excision with intraoperative triamcinolone injection yielded a rate of 33%, and keloid excision with a combination of intraoperative triamcinolone injection and postoperative radiation yielded a rate of 33%. Patients of Afro-Caribbean and African American ethnicity are more heavily affected by the formation of keloids compared with other population groups. Results of varying modalities for keloid management demonstrate that patients who received a combination of excision with intraoperative triamcinolone injection, with or without postoperative radiation, had the lowest recurrence rates compared with other treatment protocols including excision alone and excision with postoperative radiation only.

Unrecognized hemoglobin SC sickle cell disease complicated by sepsis and cholestasis

KEY POINTS A 56-year-old, Jamaica-born woman of Afro-Caribbean ethnicity presented to our emergency department with a 3-day history of abdominal pain, jaundice, subjective fever, dark urine and persistent dysuria after nitrofurantoin treatment for possible urinary tract infection. She reported that

PD17-01 DERIVATION AND EXTERNAL VALIDATION OF A RAPID RISK SCORE FOR PREDICTING CLINICALLY SIGNIFICANT PROSTATE CANCER IN MEN WITH AN MRI VISIBLE LESION: A MULTINATIONAL COHORT STUDY

PD17-01 DERIVATION AND EXTERNAL VALIDATION OF A RAPID RISK SCORE FOR PREDICTING CLINICALLY SIGNIFICANT PROSTATE CANCER IN MEN WITH AN MRI VISIBLE LESION: A MULTINATIONAL COHORT STUDY

COVID-19 vaccination during pregnancy: coverage and safety

BackgroundConcerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom; limited data exist on its uptake and safety.ObjectiveThis study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women.Study DesignThis was a cohort study of pregnant women who gave birth at St George’s University Hospitals National Health Service Foundation Trust, London, United Kingdom, between March 1, 2020, and July 4, 2021. The primary outcome was uptake of COVID-19 vaccination and its determinants. The secondary outcomes were perinatal safety outcomes. Data were collected on COVID-19 vaccination uptake, vaccination type, gestational age at vaccination, and maternal characteristics, including age, parity, ethnicity, index of multiple deprivation score, and comorbidities. Further data were collected on perinatal outcomes, including stillbirth (fetal death at ≥24 weeks’ gestation), preterm birth, fetal and congenital abnormalities, and intrapartum complications. Pregnancy and neonatal outcomes of women who received the vaccine were compared with that of a matched cohort of women with balanced propensity scores. Effect magnitudes of vaccination on perinatal outcomes were reported as mean differences or odds ratios with 95% confidence intervals. Factors associated with antenatal vaccination were assessed with logistic regression analysis.ResultsData were available for 1328 pregnant women of whom 140 received at least 1 dose of the COVID-19 vaccine before giving birth and 1188 women who did not; 85.7% of those vaccinated received their vaccine in the third trimester of pregnancy and 14.3% in the second trimester of pregnancy. Of those vaccinated, 127 (90.7%) received a messenger RNA vaccine and 13 (9.3%) a viral vector vaccine. There was evidence of reduced vaccine uptake in younger women (P=.001), women with high levels of deprivation (ie, fifth quintile of the index of multiple deprivation; P=.008), and women of Afro-Caribbean or Asian ethnicity compared with women of White ethnicity (P<.001). Women with prepregnancy diabetes mellitus had increased vaccine uptake (P=.008). In the multivariable model the fifth deprivation quintile (most deprived) (adjusted odds ratio, 0.10; 95% confidence interval, 0.02–0.10; P=.003) and Afro-Caribbean ethnicity (adjusted odds ratio, 0.27; 95% confidence interval, 0.06–0.85; P=.044) were significantly associated with lower antenatal vaccine uptake, whereas prepregnancy diabetes mellitus was significantly associated with higher antenatal vaccine uptake (adjusted odds ratio, 10.5; 95% confidence interval, 1.74–83.2; P=.014). In a propensity score–matched cohort, the rates of adverse pregnancy outcomes of 133 women who received at least 1 dose of the COVID-19 vaccine in pregnancy were similar to that of unvaccinated pregnant women (P>.05 for all): stillbirth (0.0% vs 0.2%), fetal abnormalities (2.2% vs 2.5%), postpartum hemorrhage (9.8% vs 9.0%), cesarean delivery (30.8% vs 34.1%), small for gestational age (12.0% vs 12.8%), maternal high-dependency unit or intensive care admission (6.0% vs 4.0%), or neonatal intensive care unit admission (5.3% vs 5.0%). Intrapartum pyrexia (3.7% vs 1.0%; P=.046) was significantly increased but the borderline statistical significance was lost after excluding women with antenatal COVID-19 infection (P=.079). Mixed-effects Cox regression showed that vaccination was not significantly associated with birth at <40 weeks’ gestation (hazard ratio, 0.93; 95% confidence interval, 0.71–1.23; P=.624).ConclusionOf pregnant women eligible for COVID-19 vaccination, less than one-third accepted COVID-19 vaccination during pregnancy, and they experienced similar pregnancy outcomes with unvaccinated pregnant women. There was lower uptake among younger women, non-White ethnicity, and lower socioeconomic background. This study has contributed to the body of evidence that having COVID-19 vaccination in pregnancy does not alter perinatal outcomes. Clear communication to improve awareness among pregnant women and healthcare professionals on vaccine safety is needed, alongside strategies to address vaccine hesitancy. These strategies include postvaccination surveillance to gather further data on pregnancy outcomes, particularly after first-trimester vaccination, and long-term infant follow-up.

Risk factors associated with post-operative uveitis after cataract surgery: a retrospective case-control study.

Post-operative uveitis is the most common complication after cataract surgery in the UK. The study aims to evaluate the risk of post-operative uveitis in cataract surgery patients of different ethnicity in the presence and absence of co-morbidities as well as operative complications using multivariate analysis. A retrospective case-control study of patients undergoing phacoemulsification cataract surgery between January 2018 to December 2019 at two hospital sites. Differences in demographic and clinical characteristics were compared between two groups defined by the development of post-operative uveitis. Statistically significant factors in univariate analysis were further analysed using multivariate analysis to account for confounders. One thousand and five hundred eighty seven eyes had undergone phacoemulsification cataract operations with 104 (6.6%) developing post-operative uveitis. Compared to eyes of White/Mixed/Other ethnicity, Asian and Afro-Caribbean eyes were associated with a twofold (OR 2.02, 95% CI 1.16-3.52, P = 0.013) and fivefold (OR 5.15, 95% CI 2.85-9.29, P < 0.001) risk of post-operative uveitis, respectively. Complicated surgery involving eyes with small pupil/iris hooks/Malyugin ring (OR 2.70, 95% CI 1.16-6.30, P = 0.022) and posterior capsular rupture (OR 6.00, 95% CI 2.55-14.12, P < 0.001) were associated with an increased risk of post-operative uveitis. The factors significantly associated with a post-operative uveitis outcome were patients of Asian and Afro-Caribbean ethnicity, small intra-operative pupil size, use of iris hooks or Malyugin ring and PCR. The post-operative management plan should be tailored in these group of patients with a view of early assessment and prompt management of symptoms.

High prevalence of Afro‐Caribbean ethnicity and hypoglycaemia in patients with diabetes and end stage renal disease hospitalized with COVID‐19

End stage renal disease (ESRD) is associated with a high mortality rate among patients hospitalized with COVID-19. To the best of our knowledge, there is limited data on the clinical features, ethnicity, inpatient glycaemic control and outcomes in patients with diabetes related ESRD in the literature. We report the clinical features and outcomes of 39 consecutive ESRD patients (28 on haemodialysis [HD] and 11 with renal transplant) secondary to diabetic kidney disease admitted to a university hospital with COVID-19. We observed a high prevalence of patients of Afro-Caribbean ethnicity hospitalized with COVID-19 with a 73% and 54% prevalence in renal transplant and HD groups respectively. The mortality rate of our cohort was 36%. Nearly a one-third of HD patients and one-fifth of transplant patients had hypoglycaemic events during COVID-19 hospitalization. Adjustment of diabetes treatment was frequently required. Our data highlight the importance of integrated multidisciplinary care of patients with diabetes related ESRD hospitalized with COVID-19.

Prognostic Value of Maternal Cardiovascular Hemodynamics in Women With Gestational Hypertension and Chronic Hypertension in Pregnancy

This study aimed to assess the prognostic value of cardiovascular assessment in women with gestational hypertension or chronic hypertension for the risk of preeclampsia and need for closer antenatal surveillance. This was a prospective study of pregnancies complicated by gestational hypertension or chronic hypertension presenting to St George's Hospital, between January 2015 and May 2018. A noninvasive ultrasonic cardiac output monitor was used to obtain cardiovascular variables of cardiac output (CO) and systemic vascular resistance (SVR) and weight-adjusted indices. The primary outcome was the time to development of preeclampsia in women with gestational hypertension or chronic hypertension. In women with gestational hypertension or chronic hypertension (n=149), cox-proportional hazards analysis showed that mean arterial pressure (P=0.006), Afro-Caribbean ethnicity (P=0.045), and gestational age at the time of diagnosis above 34 weeks (P<0.001) were significantly associated with increased risk of earlier preeclampsia. Women with high SVR and normal CO (adjusted hazard ratio, 2.32 [95% CI, 1.06-5.08]; P=0.035) and high SVR and low CO (adjusted hazard ratio, 7.79 [95% CI, 1.94-31.24]; P=0.003) cardiovascular profiles had significantly higher risk of earlier preeclampsia compared with women with normal SVR and normal CO. The findings of this study demonstrate that hypertensive women with increased SVR and low CO had a higher risk of developing preeclampsia sooner.

Abstract B073: Estimating genetic ancestry of commonly used cancer cell lines

Abstract Given the scarcity of human cell lines from under-represented populations available for study, it is crucial that these cell lines be accurately characterized regarding their genetic ancestry so findings can be properly contextualized. Mischaracterization of a cell line's race/ethnicity can lead to wasted time and resources and potentially publication retractions. Here we calculated genetic ancestry proportions for 22 commercially available cell lines to test the accuracy of the “race/ethnicity” categorization assigned to these cells and to provide previously unknown genetic ancestry estimates to the scientific community. To determine cellular genetic ancestry proportions, DNA was extracted from the cell lines and genotyped for ancestry informative markers using the Agena MassARRAY platform with iPLEX chemistry. Genotypes for each cell line were analyzed with STRUCTURE software using settings of 30,000 for burn-in length, 70,000 replications, and K = 3 ancestral populations, representing West African (WA), Native American (NA), and European (EA) input genotype data. Commercially available cell lines designated as “Caucasian” in ethnicity were accurately described with mean European ancestry proportions of 97% (range 92-99%). Recently, using a much smaller panel of markers, the 22Rv1 cell line was found to have 41% WA ancestry. Our genetic ancestry analysis found the 22Rv1 cell line to have mostly EA ancestry, 91% EA, while also containing a non-negligible proportion of WA ancestry (8%). Three of the commercially available cell lines ascribed “Black” race appear to be accurate (HeLa, MDA-MB-PCa2, MDA-MB-468), although two of the three, HeLa and MDA-MBPCa2, fall far below the mean of ~80% WA ancestry for US-born African Americans with 60% and 66% WA ancestry, respectively. Interestingly, the MDA-MB-468 “Black” cell line had an appreciable amount of NA ancestry, 23% NA and 77% WA ancestry, which could suggest possible Afro-Caribbean ethnicity. Most notably, the E006 cell line, designated as “Black,” is as European as the previously mentioned cell lines ascribed Caucasian ethnicity with &amp;gt; 92% EA genetic ancestry. Cell lines with unassigned ethnicity varied widely in genetic ancestry with ranges of WA, NA, and EA ancestry proportions of 1%-92%, 0%-30%, and 2%-96%, respectively. Our results suggest predominantly European ancestry for the Caucasian-designated cell lines and high variance in genetic ancestry proportions for the Black-designated cell lines. However, the E006 cell line is an example of extreme misclassification, which has led to erroneous findings in the disparities literature and leave open the possibility of mischaracterization of other unanalyzed cell lines. Genetic ancestry estimates add more advanced and detailed ancestral characterization to these cell lines and allow for better contextualization of comparisons, applicability, and significant findings. We suggest robust genetic ancestry estimates as a requirement for all current and novel cell lines used in research. Citation Format: Stanley E. Hooker Jr., Madhavi Bathina, Stacy Lloyd, Priyatham Gorjala, Ranjana Mitra, Kevin S. Kimbro, Rick A. Kittles. Estimating genetic ancestry of commonly used cancer cell lines [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B073.

P170 Predictors of renal survival in a cohort of patients with lupus nephritis with more than 30 years of follow-up

Abstract Background Despite the improvement in survival of patients with lupus nephritis (LN) over the last decades, LN is associated with progression to end-stage renal disease (ESRD) in a significant proportion of patients. We aimed to investigate the factors influencing renal survival in patients with LN. Methods Single-centre retrospective observational study. Patients with biopsy-proven proliferative, membranous or mixed LN were included. Individual clinical files were reviewed to obtain demographic, clinical, laboratory and pathological data. Cox regression analysis was performed to investigate predictors of progression to ESRD and Kaplan-Meier curves were obtained. Results We studied 187 LN patients (135 proliferative, 38 membranous and 14 mixed LN), followed for up to 42 years (mean 13±9 years). Cumulative renal survival rates at 5, 10, 15 and 20 years were 93%, 85%, 78% and 70%, respectively. In univariable analysis, urinary protein/creatinine ratio (uPCR) above 42 mg/mmol or estimated glomerular filtration rate (eGFR) below 76 mL/min/1.73m2, one year after the diagnosis of LN, were the strongest predictors of progression to ESRD, with hazard ratios (HR) of 8.081 [95%CI:1.856-35.179] and 4.985 [95%CI:1.964-12.651], respectively. HR for uPCR and eGFR at the time of diagnosis were considerably smaller (2.508 [95%CI:1.062-5.922] and 2.833 [95%CI:1.156-6.945] respectively). Other factors associated with increased risk of ESRD were Afro-Caribbean ethnicity (HR = 3.861 [95%CI:1.817-8.206]), proliferative LN (HR = 3.423 [95%CI:1.049-11.173]), not having taken antimalarials (HR = 2.180 [95%CI:1.089-4.363]) and poorly controlled diastolic blood pressure (HR = 1.016 [95%CI:1.001-1.030]). The effect of uPCR and eGFR at one year remained significant after adjusting for ethnicity, histological class, uPCR and eGFR at the time of diagnosis, use of antimalarials and diastolic blood pressure (Table 1). Conclusion uPCR above 42 mg/mmol and eGFR below 76 mL/min/1.73m2, one year after the diagnosis of LN, were the strongest predictors of progression to ESRD. Disclosures F. Farinha None. R.J. Pepper None. D.G. Oliveira None. T. McDonnell None. D.A. Isenberg None. A. Rahman None.

Incidence and Associated Risk Factors of Chemotherapy-Induced Cardiomyopathy in the African American and Afro-Caribbean Populations.

Background:Chemotherapy-induced cardiomyopathy (CICM) and heart failure are major complications of cancer therapeutics and can result in significant morbidity and mortality. There is limited data on the incidence and risk factors of CICM in African American and Afro-Caribbean patients.Methods:We performed a retrospective chart review to evaluate the baseline characteristics that may predispose to CICM. Patients were African American and Afro-Caribbean ethnicity. Data was collected between 2014 to 2018. Patients had transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA) prior to cancer therapy and every 3 months thereafter, until the end of the regimen. CICM was defined as a ≥16% reduction in LVEF or ≥10% reduction in LVEF to a value <50%.Results:A total of 230 patients were studied, with a mean age of 54±12 years with 91% were females, BMI 30±4, 81% were taking anthracyclines, 87% were on Trastuzumab while 5% were receiving both medications. The prevalence of comorbidities was as follows: hypertension 8%, diabetes mellitus 8%, ESRD 8%, dyslipidemia 8%, CAD 7%. The incidence of CICM was 7% overall, while it was 6% and 8% for patients taking Anthracyclines and Trastuzumab, respectively. CICM was associated with dyslipidemia (r= .22, p= .001), hypertension (r= .12, p= .05), baseline ejection fraction (r= −.21, p= .001) and concomitant use of radiation therapy (r= .147, p= .02), but not with age, gender, beta blocker use, angiotensin converting enzyme inhibitor use, number of chemotherapy cycles or stage of the malignancy. On multivariate analysis CICM was independently associated with baseline ejection fraction (β= −.193, P= .003) and dyslipidemia (β= −.20, P= .003).Conclusion:The incidence of CICM in African Americans and Afro-Caribbean is higher than reported in the general population. Dyslipidemia and baseline ejection fraction were seen as the major risk factors associated with the higher incidence of CICM.

Performance of Fetal Medicine Foundation Software for Pre-Eclampsia Prediction Upon Marker Customization: Cross-Sectional Study.

BackgroundFMF2012 is an algorithm developed by the Fetal Medicine Foundation (FMF) to predict pre-eclampsia on the basis of maternal characteristics combined with biophysical and biochemical markers. Afro-Caribbean ethnicity is the second risk factor, in magnitude, found in populations tested by FMF, which was not confirmed in a Brazilian setting.ObjectiveThis study aimed to analyze the performance of pre-eclampsia prediction software by customization of maternal ethnicity.MethodsThis was a cross-sectional observational study, with secondary evaluation of data from FMF first trimester screening tests of singleton pregnancies. Risk scores were calculated from maternal characteristics and biophysical markers, and they were presented as the risk for early pre-eclampsia (PE34) and preterm pre-eclampsia (PE37). The following steps were followed: (1) identification of women characterized as black ethnicity; (2) calculation of early and preterm pre-eclampsia risk, reclassifying them as white, which generated a new score; (3) comparison of the proportions of women categorized as high risk between the original and new scores; (4) construction of the receiver operator characteristic curve; (5) calculation of the area under the curve, sensitivity, and false positive rate; and (6) comparison of the area under the curve, sensitivity, and false positive rate of the original with the new risk by chi-square test.ResultsA total of 1531 cases were included in the final sample, with 219 out of 1531 cases (14.30; 95% CI 12.5-16.0) and 182 out of 1531 cases (11.88%; 95% CI 10.3-13.5) classified as high risk for pre-eclampsia development, originally and after recalculating the new risk, respectively. The comparison of FMF2012 predictive model performance between the originally estimated risks and the estimated new risks showed that the difference was not significant for sensitivity and area under the curve, but it was significant for false positive rate.ConclusionsWe conclude that black ethnicity classification of Brazilian pregnant women by the FMF2012 algorithm increases the false positive rate. Suppressing ethnicity effect did not improve the test sensitivity. By modifying demographic characteristics, it is possible to improve some performance aspects of clinical prediction tests.

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation.

BACKGROUNDPolyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless, long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.AIMTo investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODSThis single-centre observational study with a median follow up of 57 (31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasma quantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment, rejection, renal function, urologic complications, opportunistic infections, new-onset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTSBK-viremia was detected in 9.5% recipients. Initial viral load was high (≥ 10000 copies/mL) in 66.7% and low (< 10000 copies/mL) in 33.3% of these patients. Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia (95% vs 25%, P < 0.00001), nephropathy (92.5% vs 15%, P < 0.00001), and polyomavirus-related graft loss (27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity (33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50% (30% vs 14.6%, P = 0.0047), human leukocyte antigen (HLA) mismatching > 4 (26.7% vs 13.4%, P = 0.0110), and rejection within thirty days of transplant (21.7% vs 9.5%; P = 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However, viremic recipients showed higher 5-year crude cumulative (22.5% vs 12.2%, P = 0.0270) and 30-d-event-censored (22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27% (P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in 55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1% (P = 0.008) and 29.1% vs 7.2% (P < 0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.CONCLUSIONCurrent treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panel-reactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.

Men with a susceptibility to prostate cancer and the role of genetic based screening.

Prostate cancer is the second most common malignancy affecting men worldwide, and the commonest affecting men of African descent. Significant diagnostic and therapeutic advances have been made in the past decade. Improvements in the accuracy of prostate cancer diagnosis include the uptake of multi-parametric MRI and a shift towards targeted biopsy. We also now have more life-prolonging systemic and hormonal therapies for men with advanced disease at our disposal than ever before. However, the development of robust screening tools and targeted screening programs has not followed at the same pace. Evidence to support population-based screening remains unclear, with the use of PSA as a screening test limiting our ability to discriminate between clinically significant and insignificant disease. Prostate cancer has a large heritable component. Given that most men without risk factors have a low lifetime risk of developing lethal prostate cancer, much work is being done to further our knowledge of how we can best screen men in higher risk categories, such as those with a family history (FH) of the disease or those of African ancestry. These men have been reported to carry upwards of a two-fold increased risk of developing the disease at an earlier age, with evidence suggesting poorer survival outcomes. In men with a FH of prostate cancer, this is felt to be due to rare, high-penetrance mutations and the presence of multiple, common low penetrance alleles, with men carrying specific germline mutations in the BRCA and other DNA repair genes at particularly high risk. To date, large scale genome-wide association studies (GWAS) have led to the discovery of approximately 170 single nucleotide polymorphisms (SNPs) associated with prostate cancer risk, allowing over 30% of prostate cancer risk to be explained. Genomic tests, utilising somatic (prostate biopsy) tissue can also predict the risk of unfavourable pathology, biochemical recurrence and the likelihood of metastatic disease using gene expression. Targeted screening studies are currently under way in men with DNA repair mutations, men with a FH and those of Afro-Caribbean ethnicity which will greater inform our understanding of disease incidence and behaviour in these men, treatment outcomes and developing the most appropriate screening regime for such men. Incorporating a patient’s genetic mutation status into risk algorithms allows us an opportunity to develop targeted screening programs for men in whom early cancer detection and treatment will positively influence survival, and in the process offer male family members of affected men the chance to be counselled and screened accordingly.

Characteristics, socioeconomic status and ethnic variations of primary idiopathic macular hole repair in vitreoretinal centers in the United Kingdom.

The purpose of this multicentre retrospective study was to investigate the characteristics and role of ethnicity and socioeconomic status amongst patients with idiopathic macular holes (IMH) and the surgical outcome. Consecutive patients undergoing primary IMH surgery at three vitreoretinal units in the UK (King's College Hospital, London, UK, Western Eye Hospital, London, UK, Sunderland Eye Infirmary, Sunderland, UK) between January 2007 and May 2017 were included. The main outcome measure was anatomical closure of IMH. Two hundred and thirty three primary IMH surgeries were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. 69.10% of patients were European Caucasian, 6.44% were Asian, and 24.46% were Afro-Caribbean. The mean base macular hole diameter (BD) was 475.5mcm. Mean BD was 432.2mcm in European Caucasian patients, 481.3mcm in Asians (P=0.005), and 505.61mcm in Afro-Caribbeans (P=0.006). Regression analysis demonstrated that BD and Afro-Caribbean ethnicity were independent significant risk factors for surgical failure. Those who have longer duration of symptoms (Afro-Caribbeans) and leave in more deprived places (Afro-Caribbeans) in England where found to have lower success rate on macular hole closure. Asian and Afro-Caribbean patients present with larger IMH than European Caucasians. In addition to IMH base diameter, black origin and lower socioeconomic status are independent risk factors for surgical failure. This study presents a large population-based data analysis on ethnic variation in macular holes and may assist in the management and predicting the surgical outcome.

Trends in the burden of varicella in UK general practice.

Childhood varicella vaccination has not yet been introduced in the UK. To inform decision-making about future vaccine programmes, data on the burden of varicella in general practice over a 10-year period (01/01/2005-31/12/2014) was calculated by age and ethnicity, using anonymised data from >8 million individuals in the Clinical Practice Research Datalink. Varicella consultations peaked at 20 603 in 2007, then decreased annually in all age groups to 11 243 in 2014. Each year, consultation rates were common among infants, were highest among 1-3 year olds (61·2 consultations/1000 person-years in 2007, 39·7/1000 person-years in 2014) and then fell with increasing age to <1·0/1000 person-years at ages ⩾20 years. Varicella acquisition appeared to be delayed in some ethnic groups, with lower consultation rates for children aged <3 years but increased rates for older children and adults aged ⩽40 years among those of black African, Afro-Caribbean, South Asian or other Asian ethnicity. Decreasing general practice consultation rates over time could reflect changes in healthcare utilisation, with patients seeking care in alternative settings such as Accident and Emergency Departments, although current data prevent full assessment of this. Availability of data on varicella diagnoses across all health settings would enable estimation of the total healthcare burden due to varicella and the cost-effectiveness of introducing varicella vaccination.