Afro-Caribbean Patients Research Articles

Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations.

Adult T-cell leukemia-lymphoma (ATLL) is an aggressive Human T-cell Leukemia Virus Type 1 (HTLV-1)-driven malignancy. Although Western hemisphere (Afro-Caribbean and South American) patients face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletion and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-seq, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with unfavorable chronic cases. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.

Health disparities in acute myeloid leukemia: A decade-long analysis of Afro-Caribbean patients in a safety net New York City hospital.

e18515 Background: Acute Myeloid Leukemia (AML) in the Afro-Caribbean population is associated with poor outcomes due to disparities in health insurance and access to healthcare resources, among other factors, when compared to survival data in the national SEER database. This study reviews clinical characteristics and treatment outcomes of a cohort of 51 Afro-Caribbean patients who were diagnosed with AML and treated in the past 10 years in a urban safety net hospital in Brooklyn, New York. Methods: This is a retrospective review of patients diagnosed and treated for AML at New York City Health and Hospitals/Kings County from 2012 to 2022. Electronic Health Data was reviewed for clinicopathologic data and treatment outcomes. Analysis was performed through descriptive statistics with specific focus on insurance status and survival outcomes. Results: Our AML patient cohort had a mean age of 66, with 84% of patients identifying as Afro-Caribbean, and 51% being female. In this cohort, the AML risk stratification distribution based on 2022 European LeukemiaNet Risk classification includes 21 (41%) patients in the adverse-risk group, 23 (45%) patients in the intermediate-risk group, and 7 (14%) patients in the favorable-risk group. Of the 36 patients with molecular analysis data, 9 (25%) harbored a mutation in FLT3-ITD. Healthcare disparities are evident in insurance coverage, as 58% of patients lacked medical insurance, 19% had Medicare/Medicaid, and 23% had private insurance. At the time of this retrospective chart review, 35% of patients lacked any follow-up information, including appointments or status updates regarding their condition, vital status, or engagement with healthcare, possibly due to missed appointments, transfers, mortality, or other reasons. Of the 27 patients who were deemed transplant eligible, three (11%) successfully completed allogeneic bone marrow transplant. Reasons for non-transplantation include lack of a compatible donor, inadequate social support, insurance-related challenges, or patient refusal. Patients who completed induction and consolidation treatment with documented follow-up had a 23% survival rate at the five-year mark, compared to 31.7% overall survival rate reported in SEER data from 2013 to 2019. Conclusions: Our study highlights persistent healthcare disparities in Afro-Caribbean AML patients leading to poor survival outcomes. Despite treatment advancements, challenges related to insurance coverage, social support, follow-up care, and access to restricted, advanced care remain. Addressing these disparities calls for targeted interventions to enhance access and support systems for this vulnerable population.

Overall and metastasis-free survival of Afro-Caribbean patients with biochemical recurrence after radical prostatectomy.

Early salvage radiotherapy is indicated for patients with biochemical recurrence after radical prostatectomy. However, for various reasons, certain patients do not benefit from this treatment (OBS) or only at a late stage (LSR). There are few studies on this subject and none on a "high-risk" population, such as patients of African descent. Our objective was to estimate the metastasis-free (MFS) and overall survival (OS) of patients who did not receive salvage radiotherapy, and to identify risk factors of disease progression. This was a single-center retrospective study that included 154 patients, 99 in the OBS group and 55 in the LSR group. All were treated by total prostatectomy for localized prostate cancer between January 2000 and December 2020 and none received early salvage radiotherapy after biochemical recurrence. Baseline characteristics were similar between groups, except for the time to biochemical recurrence. The median follow-up was 10.0 and 11.8 years for the OBS and LSR groups, respectively. The median time from surgery to LSR was 5.1 years. The two groups did not show a significant difference in MFS: 90.6% at 10 years for the OBS group and 93.3% for the LSR group. The median MFS was 19.8 and 19.6 years for the OBS and LSR groups respectively. OS for the OBS group was significantly higher than that for the LSR group (HR: 2.14 [1.07-4.29]; p = 0.03), with 10-year OS of 95.9% for the OBS group and 76.1% for the LSR group. Median OS was 16 and 15.6 years for the OBS and LSR groups, respectively. In this study, we observed satisfactory metastasis-free and OS rates relative to those reported in the scientific literature. The challenge is not to question the benefit of early salvage radiotherapy, but to improve the identification of patients at risk of progression through the development of molecular and genomic tests for more highly personalized medicine.

Survey of Potential Disparity Issues Among Minority Stroke Survivors in Central Brooklyn.

Medical data and information are ubiquitous due to internet availability. However, most people persist in using and trusting their healthcare professionals for health information. They are increasingly flooded with health information from diverse sources such as the internet, community-based organizations, and family or friends. It is crucial to understand where stroke patients vary in the use and trust of health information to improve their conditions. This pilot study aimed to better understand the nature of the problems confronted by stroke patients, such as the source of reliable health information, trust in the healthcare system, and technology trend awareness. African American and Afro-Caribbean stroke patients (n=64) residing in Central Brooklyn, New York, participated in a survey. The results showed that physicians remained the most highly trusted information sources for stroke patients, particularly among patients with higher education, irrespective of the available communication sources.

Longitudinal follow-up of mixed connective tissue disease and overlapping autoimmune diseases of childhood onset in the Afro-descendant population of the French West Indies

IntroductionOverlap autoimmune syndromes (OAS) and mixed connective tissue disease (MCTD) are rare in children. We performed a retrospective, longitudinal and descriptive study of Afro-Caribbean patients from the French West Indies followed for MCTD and OAS to describe their characteristics and outcomes during childhood.MethodsRetrospective study from January 2000 to 2023. Listings of patients were obtained from multiple sources: computerized hospital archives and national hospital-based surveillance system, registry of pediatricians and adult specialists in internal medicine and the national registry for rare diseases. MCTD was defined according to Kasukawa’s criteria. OAS was defined as overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis/autoimmune myositis (DM/AM).ResultsSixteen patients were included over a 23-year period (10 MCTD and 6 OAS). The incidence was 0.23 per 100,000 children-years. The mean age at diagnosis was 11.9 years old (2.4–17) with median follow up of 7.9 years (2.1–19.6). SLE phenotype was present in the highest, followed by SSc and DM/AM. Patients had an average of three flares during childhood (1–7). A quarter (25%) had symptomatic pulmonary arterial hypertension (PAH). Ninety-four percent received steroids during follow-up and 88% required a corticosteroid-sparing therapy. Three patients (19%) developed SLE after more than 10y of follow-up. There were no death and no chronic organ failure.ConclusionThis is the largest pediatric cohort of MCTD and OAS in Afro-descendant patients treated in a country with a high standard of care. The clinical evolution did not differ between MCTD and OAS. The main complication was PAH, more frequent in our cohort.

The Genetic Paradigm of Hereditary Breast and Ovarian Cancer (HBOC) in the Afro-Caribbean Population.

Differences in tumor biology and genetic predisposition have been suggested as factors influencing overall survival and increased mortality in Black breast and ovarian cancer patients. Therefore, it is key to evaluate genetic susceptibilities in Afro-Caribbean patients because the black population in the US is not homogeneous. Identifying a high incidence of hereditary breast and ovarian cancer (HBOC) in Afro-Caribbean countries can lead to understanding the pattern of inherited traits in US-Caribbean immigrants and their subsequent generations. The paucity of projects studying the genetic landscape in these populations makes it difficult to design studies aimed at optimizing screening and prophylaxis strategies, which in turn, improve survival and mortality rates. This scoping review identifies and categorizes current research on the genetic paradigm of HBOC in the Afro-Caribbean population. We performed an evaluation of the evidence and generated a summary of findings according to preferred reporting items for systematic review and meta-analysis (PRISMA) Extension for Scoping Reviews guidelines. We included articles that assessed the incidence and prevalence of pathologic germline mutations and experience/barriers for genetic testing in Afro-Caribbean Countries and US-Caribbean patients. Our results highlight countries where genetic landscapes remain severely understudied and support recommending multigene testing in Caribbean-born patients. They highlight a need for further research on the genetic paradigm of HBOC in the Afro-Caribbean population to improve genetic testing/counseling and the subsequent adoption of early detection and risk reduction strategies.

Phenotypic Profiles Among 72 Caucasian and Afro-Caribbean Patients with Antisynthetase Syndrome Involving Anti-PL7 or Anti-PL12 Autoantibodies

ObjectivesAntisynthetase syndrome (ASyS) is a rare autoimmune disease. We aimed to determine clinical, biological, radiological, and evolutive profiles of ASyS patients with anti-PL7 or anti-PL12 autoantibodies. MethodsWe performed a retrospective study that included adults with overt positivity for anti-PL7/anti-PL12 autoantibodies and at least one Connors’ criterion. ResultsAmong 72 patients, 69% were women, 29 had anti-PL7 and 43 anti-PL12 autoantibodies, median age was 60.3 years, and median follow-up period was 52.2 months. At diagnosis, 76% of patients had interstitial lung disease, 61% had arthritis, 39% myositis, 25% Raynaud's phenomenon, 18% mechanic's hands, and 17% had fever. The most frequent pattern on initial chest computed tomography was non-specific interstitial pneumonia and 67% had fibrosis at last follow-up. During follow-up, 12 patients had pericardial effusion (18%), 19 had pulmonary hypertension (29%), 9 (12.5%) had neoplasms, and 14 (19%) died. Sixty-seven patients (93%) received at least one steroid or immunosuppressive drug. Patients with anti-PL12 autoantibodies were younger (p=0.01) and more frequently exhibited anti-SSA autoantibodies (p=0.01); patients with anti-PL7 autoantibodies had more severe weakness and higher maximum creatine kinase levels (p=0.03 and 0.04, respectively). Initial severe dyspnoea was more common in patients from the West Indies (p=0.009), with lower predicted values of forced vital capacity, forced expiratory volume in 1s, and total lung capacity (p=0.01, p=0.02, p=0.01, respectively) contributing to a more severe ‘respiratory’ initial presentation. ConclusionsThe high mortality and significant numbers of cardiovascular events, neoplasms and lung fibrosis in anti-PL7/12 patients justify close monitoring and question addition of antifibrotic drugs.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: CAR T-cell therapy has revolutionised treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL), but it is unclear whether access and clinical benefit is equal for ethnic minorities and deprived communities. We analysed outcomes of LBCL patients approved for CD19 CAR T at 2 UK centres serving a large and diverse population, according to ethnicity and socioeconomic deprivation. Methods: Consecutive patients with r/r LBCL approved for 3L axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between January 2019 and December 2022 at King’s College Hospital London and University Hospital Birmingham were included. Data on deprivation was obtained through the Index of Multiple Deprivation (IMD) 2020 according to patients’ postcode. The IMD ranks between 1 and 10 and includes different factors relating to healthcare inequalities (e.g., income, employment, education). Patients were grouped into high (IMD 1–3) and low deprivation (8–10). Results: 245 patients were included, 193 approved for axi-cel, 52 for tisa-cel. Deprivation data were available for 218 patients. The product choice did not differ according to ethnic or deprivation groups. Patients’ median age was 61y. Ethnic groups were as follows: 214/245 (87%) White, 22 (9%) Asian, 7 (3%) Afro-Caribbean, 2 mixed race. 21% of patients were from areas of high deprivation. 53% of patients travelled >50 km to the CAR T centre, 25% >100 km. 82% patients were infused, with no significant difference according to ethnicity, deprivation or distance to the centre. Ethnic minority patients came from more deprived areas versus white patients (med. IMD 7 vs. 5 vs. 4 in White, Asian and Afro-Caribbean patients, respectively; p = 0.04). Distance to the CAR T centre was longer in white versus ethnic minority patients (med. 59 vs. 18 km, p = 0.03). There were more patients with ECOG PS 0 from low deprivation areas (46% vs. 31%; p = 0.04), otherwise no significant differences of baseline characteristics, i.e., LDH, bulk, stage, IPI, bridging response, or vein-to-vein time according to ethnicity or deprivation. No difference was observed in high-grade ICANS, incidence of CRS, ICU requirement, tocilizumab/steroid use or non-relapse mortality with respect to ethnicity or deprivation. CAR T response and progression-free survival were similar across ethnic and deprivation groups. Among patients who progressed after CAR T, those from areas of low deprivation were more likely to receive further therapies (79% vs. 48%, p = 0.02). Patients from low deprivation areas had better overall survival (OS; 1-y OS 61% vs. 45%, p = 0.04). Keywords: Cancer Health Disparities, Cellular therapies, Immunotherapy No conflicts of interests pertinent to the abstract.

A population pharmacokinetic model to guide clozapine dose selection, based on age, sex, ethnicity, body weight and smoking status.

Guidance on clozapine dosing in treatment-resistant schizophrenia is based largely on data from White young adult males. This study aimed to investigate the pharmacokinetic profiles of clozapine and N-desmethylclozapine (norclozapine) across the age range, accounting for sex, ethnicity, smoking status and body weight. A population pharmacokinetic model, implemented in Monolix, that linked plasma clozapine and norclozapine via a metabolic rate constant, was used to analyse data from a clozapine therapeutic drug monitoring service, 1993-2017. There were 17 787 measurements from 5960 patients (4315 male) aged 18-86 years. The estimated clozapine plasma clearance was reduced from 20.2 to 12.0L h-1 between 20 and 80 years. Model-based dose predictions to attain a predose plasma clozapine concentration of 0.35 mg L-1 was 275 (90% prediction interval 125, 625) mg day-1 in nonsmoking, White males weighing 70 kg and aged 40 years. The corresponding predicted dose was increased by 30% in smokers, decreased by 18% in females, and was 10% higher and 14% lower in otherwise analogous Afro-Caribbean and Asian patients, respectively. Overall, the predicted dose decreased by 56% between 20 and 80 years. The large sample size and wide age range of the patients studied allowed precise estimation of dose requirements to attain predose clozapine concentration of 0.35 mg L-1 . The analysis was, however, limited by the absence of data on clinical outcome and future studies are required to determine optimal predose concentrations specifically in those aged over 65 years.

Abstract P4-03-05: HER2 + Breast Cancer in Afro-Caribbean Women in New York City

Abstract Background: Human Epidermal Growth Factor receptor 2 (HER2) protein overexpression and/or amplification positive breast cancer accounts for 14% of breast cancer cases in the United States. The use of anti-HER2 targeted therapy in combination with chemotherapy has resulted in better response rates leading to better outcomes in patients with this breast cancer subtype. Few studies directly investigate breast cancer outcomes in Afro-Caribbean women in the U.S, and fewer studies have investigated HER2 positive (HER2+) disease in this patient group. We describe the clinicopathologic characteristics and outcomes of HER2+ breast cancer in this minority patient group. Methods: This is a retrospective study conducted at Kings County Hospital (KCH), a public hospital in Brooklyn, a New York City borough with the highest population of Afro-Caribbeans in the United States, outside of Miami, Florida. Data of patients diagnosed with breast cancer from 2015-2018 was collected from the hospital’s tumor registry. Clinical and pathologic data was collected and analyzed with descriptive statistics and Chi-square testing. Results: A total of 299 women with breast cancer were screened and 18% (54) had HER2+ disease. 63% (34) of these patients were post-menopausal, with median age 56. 78% self-identified as Afro-Caribbean. 19% (11) of patients reported first- or second-degree relatives with a breast cancer diagnosis, 22% (13) reported first-degree relative with non-breast malignancy. Half of the patients younger < 45 years age reported a positive family history of any type of cancer. 74% of patients presented with Nottingham Grade 3 disease, 31% with localized disease, without lymph node involvement, 52% with regional lymph node involvement, and 17% with distant metastasis. 63% of patients were estrogen receptor (ER) positive and 37% were ER negative. Post-menopausal women presented with higher rates of lymph node involvement at 70.4% vs. 50% in pre-menopausal women (p=0.17). 41% (22) of patients received neoadjuvant chemotherapy while 31% received adjuvant therapy with standard chemotherapy and anti-HER2 targeted treatment. Of the 22 patients who received neoadjuvant treatment, 14% had complete pathologic response, 68% had partial response, and 18% had disease progression. Treatment response to neoadjuvant therapy was independent of lymph node status (90.9% in local disease vs. 85.7% in lymph node involvement, p=0.66). The median progression free survival was 48 months, overall survival at 7 years was not reached, and mortality rate was 16.7%. Conclusions: In our analysis, Afro-Caribbean patients with HER2+ breast cancer presented with high grade tumor, high incidence of regional lymph node involvement, and ER positive tumors. Noteworthy was the presence of strong family history of cancers, suggestive of familial or inherited cancers. Pathologic complete response to neoadjuvant chemotherapy was remarkably less than anticipated, and further research is warranted to study tumor biology and responses to standard HER2 systemic therapies in these patients.

Clozapine: Dose, Sex, Ethnicity, Smoking Habit, Age, Body Weight, and Plasma Clozapine and N-Desmethylclozapine (Norclozapine) Concentrations in Clinical Practice.

Guidance on clozapine dosing in treatment refractory schizophrenia is based largely on data from young adult male White patients. This study aimed to audit the plasma clozapine and N-desmethylclozapine (norclozapine) concentrations attained in male and female patients of different ethnicity and smoking habit. The effect of dose, sex, ethnicity, age, body weight, and smoking habit on plasma clozapine and norclozapine concentrations were studied using data from a therapeutic drug monitoring service, 1993 to 2017. There were 371,610 samples (48,098 patients, 32,855 male). Ethnicity was recorded for 763 Afro-Caribbean, 536 Asian, and 7940 White patients. Males were prescribed significantly higher median doses than females but attained significantly lower median plasma clozapine and norclozapine concentrations. Asian and Afro-Caribbean males were prescribed significantly lower and higher median doses, respectively, than White males but attained significantly higher and lower median plasma clozapine and norclozapine concentrations, respectively. Data from 78,431 samples (23,516 patients) were analyzed using a linear mixed model. The predicted dose to attain a predose plasma clozapine concentration of 0.35 mg/L in a nonsmoking White male aged 40 years, with weight of 70 kg, and plasma clozapine-norclozapine ratio of 1.32 was 344 mg/d (95% confidence interval, 227-526 mg/d). The predicted dose was 33% higher and 20% lower in otherwise analogous Afro-Caribbean and Asian patients, respectively. In all cases, the predicted dose was increased by 36% in smokers and decreased by 22% in females. Research is needed to further investigate the complex relationships between dose, sex, ethnicity, plasma clozapine and norclozapine concentrations, and clinical outcome such as weight gain.

Lumbar Spinal Stenosis Treatment: Is Surgery Better than Non-Surgical Treatments in Afro-Descendant Populations?

(1) Background: Limited data are available on lumbar spine stenosis management in sub-Saharan African populations and Afro-descendant patients are underrepresented in European and US clinical trials. We aimed to compare the clinical response between decompressive surgery and conservative treatments in a population of self-reported Afro-Caribbean patients with lumbar spine stenosis over a 2-year follow-up period. (2) Methods: Prospective cohort of 137 self-reported Afro Caribbeans with lumbar spine stenosis based on clinical and radiological criteria. Patients were assigned to decompression surgery or to conservative treatments according to their outcome after a first course of steroid epidural injection and their preferences. The primary outcome was evolution of the Oswestry disability index at 3 months (3 M), 12 M, 18 M and 24 M follow-up. (3) Results: Decrease of ODI was significantly more important in the "decompression surgery" arm compared to "conservative treatment" arm at 3 M, 12 M and 18 M: -17.36 vs. 1.03 p < 10-4; -16.38 vs. -1.53 p = 0.0059 and -19.00 vs. -4.52 p = 0.021, respectively. No difference was reported at 24 M. (4) Conclusions: In this first comparative study between surgery and conservative treatments in an exclusively afro-descendant lumbar spine stenosis cohort, we report long term superiority of decompression surgery versus conservative treatments over an 18-month period.

Systemic lupus of pediatric onset in Afro-Caribbean children: a cohort study in the French West Indies and French Guiana

BackgroundSystemic diseases of pediatric onset are more frequent in the Afro-Caribbean population. We performed a study of patients followed in the French overseas departments of America (FOAD) for pediatric systemic lupus erythematosus (pSLE). The aims were to describe the clinical and biological specificities during childhood in this population.MethodsA retrospective study was conducted between January 2000 and September 2021. Patients with pSLE were identified from multiple sources: computerized hospital archives, registry of referring pediatricians, adult specialists in internal medicine and the French National Registry for rare diseases. We studied SLE with pediatric onset defined by international criteria.ResultsOverall, 2148 patients were identified, of whom 54 were included. The average follow-up was 8.3 years (range: 0.3—25 years). We observed an increase in new diagnoses over time. At onset, pSLE patients had a median of 10 SLICC criteria (range: 4–12), and the median EULAR/ACR 2019 score was 38 (12—54). At onset, one third of patients had renal involvement, 15% had neurolupus and 41% cardiac involvement. During childhood, 54% had renal involvement, and 26% suffered from neurolupus. Patients suffered a median of 3 flares during childhood, and 26% had more than 5 flares. Patients with younger age at onset had worse outcomes than those who were older at diagnosis, i.e., more flares (median 5, p = 0.02) and requiring an average of 4 background therapies (p = 0.04).ConclusionThe outcomes of Afro-Caribbean patients were similar to those in Western population, but with worse disease activity at onset. Further studies should be performed to identify the genetic and environmental factors in this population.

Characterising treatment outcomes of patients achieving quarterly aflibercept dosing for neovascular age-related macular degeneration: real-world clinical outcomes from a large tertiary care centre.

To evaluate the proportion of patients achieving a 12-week (q12) aflibercept dosing interval in patients with neovascular age-related macular degeneration (nAMD). Retrospective, comparative, non-randomised electronic medical record (EMR) database study of the Moorfields database of treatment-naïve nAMD eyes. Extraction criteria included at least 7 aflibercept injections in first year of treatment, AMD in the diagnosis field of EMR, and minimum of 1 year follow-up data. There were 2416 eyes of 2163 patients started on anti-vascular endothelial growth factor (anti-VEGF) between 01-11-2013 & 14-02-2020 who had received at least 7 aflibercept intravitreal injections (electronic database accessed March 2021). Of these, 1674 (68%) eyes of 1537 patients had at least one q12 dosing interval (>=84 and < =98 days between injections) during the first 2 years of treatment. This included 926 (61.8%) female patients and 856 (right eyes age at 1st injection), 936 (62.4%) Caucasian, and 32 (2.1%) Afro-Caribbean patients. The median time to the first q12 injection (95% confidence interval) was 1.76 years (1.70-1.86) with mean (±SD) of 11.8 (±6.0) injections. Visual acuity (ETDRS letters) of the eyes without q12 injection and eyes with a q12 injection was 57.9 ± 14.7 and 56.7 ± 14.8 respectively at baseline, 61.4 ± 18.1 and 63.0 ± 15.9 respectively at 12 months and 61.2 ± 20.1 and 61.1 ± 17.8 respectively at 24 months. 68% of eyes were able to achieve a q12 injection dose within the first 2 years of treatment. Eyes achieving a q12 injection in the first 2 years achieved a similar visual acuity outcome at both 1 and 2-year follow-up to those unable to do so, with a fewer number of total injections.

Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers

Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad’s phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of “seronegative” SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2–7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients’ stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns’ interpretation. The gold-standard technique for autoantibodies’ identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients.

Long-Term Complications of Open and Robot-Assisted Laparoscopic Radical Prostatectomy in an Afro-Caribbean Population.

BackgroundWith the Afro-Caribbean population increasing in the United States, their complication profiles following open (ORP) and robot-assisted laparoscopic (RALP) radical prostatectomy warrants investigation. The purpose of this pilot study was to evaluate differences in long-term complications between ORP and RALP in Afro-Caribbeans.MethodsA retrospective review of patients undergoing ORP or RALP between April 2010 and August 2019 at an academic medical center and county hospital was conducted. Patients who identified as Afro-Caribbean with complete data were analyzed. Complications were classified using the Clavien-Dindo system. Age, transrectal ultrasound prostate volume, preoperative prostate-specific antigen, Gleason scores, and long-term complications (persisting to at least 18 months postoperatively) were compared between procedures using the Mann-Whitney U test or Fisher’s exact test for statistical significance. Multivariable logistic regression was used to assess the odds of complications.ResultsThis study included 53 Afro-Caribbean patients (mean age±SD; 65.9±6.8 years, 30 ORP, and 23 RALP). Patients treated by RALP were younger and had lower Gleason scores. Patients who were treated by RALP had a lower association to having ≥1 complications compared to those treated by ORP (OR=0.28, 95%CI 0.09-0.89, p=0.024). In addition, >60% of complications had a Clavien-Dindo grade≤II for both procedures. RALP resulted in fewer grade II complications compared to ORP (OR=0.25, 95%CI 0.08-0.81, p=0.046).ConclusionsTreatment of Afro-Caribbeans with RALP allows for fewer complications, especially Clavien-Dindo Grade II complications. While previous investigations show that Black populations experience more complications when treated with ORP or RALP compared to other groups, their complication profile is likely not homogenous when considering their sub-ethnic background and must be investigated to understand optimal interventions for prostate cancer.

Cerebral Ischemic Events: An Overlooked Complication of Transthyretin Cardiac Amyloidosis in Afro-Caribbean Patients

AimThe link between transthyretin cardiac amyloidosis (CATTR), and cerebral ischemic events (CIE) has only been hinted at till now, impeding progress in patient management. We seek to evaluate the frequency and characteristics of CIE in Afro-Caribbean patients followed for CATTR at our institution.MethodsIn this single-center retrospective observational study, Afro-Caribbean patients followed for CATTR between July 2005 and October 2019 were included. Occurrence of CIE was investigated, and their cardioembolic origin determined. Analysis of patient characteristics was conducted according to CIE and CATTR profiles.ResultsOverall, 120 CATTR patients were included: 17 wild-type ATTR (14.2%), 73 ATTR-V122I (60.8%), and 22 ATTR-I107V (18.3%). Thirty-six patients (30.0%) presented with CIE, including three transient ischemic attacks and 33 permanent ischemic strokes (75.8% with a cardioembolic pattern). CIE was concomitant with CATTR diagnosis in 16 (16/36: 44.4%) patients, while 14 patients (14/36: 38.9 %) experienced CIE over a median CATTR follow-up of 2.0 years (min-max range: 0.8–4.4 years). CATTR-CIE patients presented with atrial fibrillation (66.7%), left atrial enlargement (77.8%), a CHA2DS2-VASc ≥ 3 (97.2%) and a high anticoagulant intake (75.0%). Multivariate analysis retained only a high CHA2DS2-VASc score as an independent predictor of CIE risk (Hazard Ratio [95% CI]: 12.03 [1.62–89.24]).ConclusionConcomitant CIE, and CATTR diagnosis, potentially carries a worse prognosis. A CHA2DS2-VASc score ≥3 seems to be a strong and independent predictive factor of CIE in CATTR patients. Further studies are needed to assess the efficacy and timeliness of anticoagulation in CATTR patients, independently of atrial fibrillation.

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.

Changes in Pregnant Patients’ Beliefs About COVID-19

COVID-19 is a novel coronavirus with data suggesting a more serious clinical course in pregnancy. We aimed to assess changes in knowledge, behaviors, and intentions of pregnant women regarding COVID-19. This was a cross-sectional survey study of 58 and 77 predominantly African-American and Afro-Caribbean pregnant patients presenting for prenatal care in Brooklyn, NY in 2020 (during the first surge of the pandemic) and 2021, respectively. Descriptive and inferential statistics were performed. Many beliefs and intentions were unchanged between 2020 and 2021 (e.g. believing pregnant women were at higher risk of COVID-19 infection and subsequent ICU admission due to pregnancy, having the desire to breastfeed, among others). Other beliefs and behaviors changed between 2020 and 2021 (fewer women believed they received information from their provider regarding COVID-19 and fewer would miss a prenatal visit for fear of COVID-19 contagion). Patients’ behaviors and intended behaviors in both 2020 and 2021 were directly influenced by their beliefs, many of which were based on unsupported data regarding COVID-19 and pregnancy (ie: babies were at increased risk of being born with congenital malformation following a mother’s COVID-19 infection). Patients who held these beliefs were more likely to say that they did not attend prenatal visits and did not receive information from their provider regarding COVID-19. Knowledge of patient beliefs is useful for structuring care as the pandemic evolves. This study demonstrates that pregnant patients make decisions regarding behaviors based on beliefs grounded in misinformation. Accordingly, it is the provider’s responsibility to ensure that beliefs regarding COVID-19 are based in fact, so patients can make informed decisions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10900-021-01058-0.

Notable Patterns in the Genomic Landscape of Adult T-Cell Leukemia/Lymphoma Encountered in HTLV-1 Endemic Western World Regions

Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognosis and associated with clonal T-cell expansion driven by Human T-Lymphotropic Virus 1 (HTLV-1) infection. Comprehensive genomic studies in Japan have identified recurrent alterations affecting TCR-NF-kB signaling (i.e. PRKCB, PLCG1, CARD11, VAV1, and IRF4), T-cell trafficking pathways (i.e. CCR4 and CCR7), and the tumor suppressor genes CDKN2A and TP53. HTLV-1 endemic regions include Africa, the Caribbean, and South America in addition to Japan. Retrospective studies from the Western population have reported distinctive features from the Japanese cohort, e.g. younger age, more common lymphomatous presentation, and worse outcomes. Our group sought to evaluate the unique molecular features of ATLL in a large cohort of patients from the Caribbean and South America.Methods: We performed a multimodal genomic study on specimens from 169 patients encountered in the United States (Miami), Peru, Brazil, France, and Spain. Data types included Oncoscan/Copy Number Variation (CNV) data for 129 patients, RNA-seq data for 97 patients, and whole exome sequencing (WES) data for 125 patients. Patients were ethnically classified based upon single nucleotide polymorphisms, under 3 main groups: African (n=80), native American (n= 32), or South Asian/Islander (n=12). 46 specimens without WES data could not be ethnically classified. Somatic variants were called using Mutect. Putative driver mutations were identified by frequency-based criteria. CNV significance was determined using GISTIC2.0. Data were compared to whole exome and targeted sequencing data published by Kataoka et al.Results: Our cohort replicated trends reported in Japanese datasets but included several distinctive findings. South American and Caribbean patients had fewer mutations in CCR4 and CD58. Three putative tumor suppressors not previously implicated in ATLL were identified based on recurrent damaging mutations. These included ANKRD11 (n=3), DGKZ (n=3), and PTPN6 (n=3). Both ANKRD11 and PTPN6 were only mutated in Afro-Caribbean patients with aggressive (acute and lymphomatous) cases. CNV analysis revealed ANKRD11 deletions in a significant portion of cases (n=16).As previously reported, STAT3 mutations were more common in indolent subtypes. IRF4 mutations (n=14) or amplifications (n=19) were only observed in aggressive ATLL subtypes. L70V was the most common IRF4 variant (n=5). Among Japanese samples, K59R mutations were seen twice as often as L70V mutations. Both K59R and L70V are located within the IRF4 DNA binding domain. In samples from patients with disease relapse (N = 10), IRF4 was the only gene mutated significantly more often (p = 0.03). 3 of 10 patients who were previously treated with interferon (IFN)-based therapy relapsed with new IRF4 mutations (L70V n=2, and K59R n=1), suggesting IRF4 may be associated with IFN resistance.A total of 11 patients in the Western cohort had FOXO3 mutations including R177W (n=7) and D199N (n=3) variants. These only occurred in Afro-Caribbean patients with aggressive subtypes. R177W is located within the FOXO3DNA binding domain, suggesting that dysregulation of its transcriptional targets may contribute to disease. In the Japanese cohort, only one patient had a FOXO3 mutation, (D199N). The majority of primary ATLL samples analyzed by Western Blot showed significantly reduced or no expression of FOXO3, or ANKRD11.Conclusion: The genomic landscape of ATLL encountered in patients from South America and the Caribbean resembles that of ATLL in Japanese patients. However, our study identified novel variants and tumor suppressor genes not previously implicated in ATLL that differ from the Japanese population. Furthermore, we correlate our genomic analysis with clinical findings to implicate ATLL driver genes in IFN resistance and disease prognosis. Functional Studies to determine the prognostic and functional roles of the gene alterations we identified in ATLL are ongoing. DisclosuresGru: StemLine: Honoraria, Research Funding, Speakers Bureau; CRISPT Therapeutics: Research Funding; Innate Pharma: Research Funding.