Sickle Cell Hemoglobinopathies Research Articles

Unraveling the Complexity of Vaso-Occlusive Crises in Sickle Cell Disease: Insights from a Resource-Limited Setting.

Background/Objectives: This study investigated vaso-occlusive crises (VOCs) in sickle cell disease in Lubumbashi, Democratic Republic of Congo, aiming to understand the disease complexities amidst limited resources. With sickle cell hemoglobinopathies on the rise in sub-Saharan Africa, this nine-year study explored factors associated with VOCs and hematological components. Methods: This study comprised 838 patients, analyzing VOCs and hematological changes over time. Demographic characteristics and blood composition changes were carefully categorized. A total of 2910 crises were observed and managed, with analyses conducted on severity, localization, and age groups using statistical methods. Results: The majority of crises were mild or moderate, primarily affecting osteoarticular regions. Statistical analysis revealed significant disparities in crisis intensity based on location and age. The association between blood samples and the number of comorbidities was investigated. Significant positive associations were found for all parameters, except monocytes, indicating a potential link between blood variables and complication burden. Survival analysis using Cox regression was performed to predict the probability of experiencing a second crisis. No significant effects of medication or localization were observed. However, intensity (p < 0.001), age (p < 0.001), and gender (p < 0.001) showed significant effects. Adjusted Hazard Ratios indicated increased risk with age and male gender and reduced risk with mild or severe crisis intensity compared to light. Conclusions: This research sheds light on the complexities of VOCs in resource-limited settings where sickle cell disease is prevalent. The intricate interplay between clinical, laboratory, and treatment factors is highlighted, offering insights for improved patient care. It aims to raise awareness of patient challenges and provide valuable information for targeted interventions to alleviate their burden.

A Comprehensive Review of Pregnancy in Sickle Cell Disease.

Sickle cell hemoglobinopathies encompass a range of qualitative and quantitative hemoglobin disorders that are inherited genetically. This group of disorders includes sickle cell beta thalassemia, sickle cell trait, and sickle cell disease (SCD). Globally, SCD is the most common disorder. Even epidemiological data suggests the majority of diseases, as well as traits, are concentrated in Sub-Saharan Africa, North-East Africa, the Middle East, and India. The physiological changes in pregnancy predispose to an increased risk of catastrophic events like a vaso-occlusive crisis, thromboembolic events, and their related sequelae, leading eventually to villous infarction, necrosis, and fibrosis leading to compromising uteroplacental circulation. Conversely, the mother may exhibit exacerbated symptoms of gestational hypertension, placental abruption, preterm labor, and venous thromboembolism. Although this disease is manageable, it has the potential to adversely impact maternal and child health on a national level. The chances of severe complications in the pregnant state affecting both mother and fetus attract due attention of health services towards redefining and researching this disease and its management frequently. The literature review on the following situation advocates the general treatment to be observed under the headings of preconceptual care, strengthened antenatal care, strict intranatal care, and compliant post-natal care. Preconceptually, genetic screening of couples, with education on the adverse effects of the disease, comes as the first line of management. Newer facilities like preimplantation genetic diagnosis and celocentesis may even allow for early diagnosis as well as help patients who do not wish to terminate the pregnancy by selective transfer of unaffected embryos. This may be combined with an extensive evaluation of the psychosocial aspect and socioeconomic status of couples who administer vaccines as prophylaxis for preventable diseases. Strengthening antenatal care is associated with routine blood investigations for every registered antenatal patient with adequate awareness about the conditions that precipitate the crisis. All patients should be prophylactically treated with appropriate doses of aspirin, iron, folic acid, and multivitamins. Radiological examinations by ultrasonography may be used to monitor placenta previa, abruption, or preterm labor. Later in pregnancy, it should be recommended to performbiophysical profiling and assessment of umbilical artery flow. Intranatal care deals with strict-term institutional delivery of all sickle cell-diseased mothers with a preference for vaginal delivery. Post-natal care requires a precise assessment of blood loss during labor to initiate transfusion therapy as soon as needed. Exclusive breastfeeding, with the importance of early initiation of it, must be emphasized. Screening of neonates as quickly as possible must be done for hemoglobinopathies. Through this review, authors are trying to make aware of the complications that can be faced during pregnancy in SCD patients, its prevention, and its treatment according to various new guidelines and research available.

Multicenter Long-Term Follow-Up of Allogeneic Hematopoietic Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials

Omidubicel is an umbilical cord blood (UCB)-derived ex vivo-expanded cellular therapy product that has demonstrated faster engraftment and fewer infections compared with unmanipulated UCB in allogeneic hematopoietic cell transplantation. Although the early benefits of omidubicel have been established, long-term outcomes remain unknown. We report on a planned pooled analysis of 5 multicenter clinical trials including 105 patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent omidubicel transplantation at 26 academic transplantation centers worldwide. With a median follow-up of 22 months (range, .3 to 122 months), the 3-year estimated overall survival and disease-free survival were 62.5% and 54.0%, respectively. With up to 10 years of follow-up, omidubicel showed durable trilineage hematopoiesis. Serial quantitative assessments of CD3+, CD4+, CD8+, CD19+, CD116+CD56+, and CD123+ immune subsets revealed median counts remaining within normal ranges through up to 8 years of follow-up. Secondary graft failure occurred in 5 patients (5%) in the first year, with no late cases reported. One case of donor-derived myeloid neoplasm was reported at 40 months post-transplantation. This was also observed in a control arm patient who received only unmanipulated UCB. Overall, omidubicel demonstrated stable trilineage hematopoiesis, immune competence, and graft durability in extended follow-up.

The Effect of Sickle Cell Hemoglobinopathy on Pregnancy, Labor, Puerperium, and Fetal Outcome: A Retrospective Cohort Study From a Single Centre.

Sickle cell disease (SCD) is a major risk factor as far as pregnancy and obstetric complications are concerned. It possesses major perinatal and postnatal mortality. The management of pregnancy along with SCD requires a multispecialty team consisting of hematologists, obstetricians, anesthesiologists, neonatologists and intensivists. The objective of this study was to investigate the effect of sickle cell hemoglobinopathy on pregnancy, labor, puerperium, and fetal outcome in the rural and urban localities of Maharashtra, India. The present study is a comparative retrospective analysis of 225 pregnant women with SCD (genotype AS and SS) and 100 age- and gravida-matched pregnant women with normal hemoglobin (genotype AA) as a control who were treated between June 2013 to June 2015, in Indira Gandhi Government Medical College (IGGMC), Nagpur, India. We analyzed various data regarding obstetrical outcomes and complications in sickle cell disease mothers. Out of 225 pregnant women, 38 (16.89%) were diagnosed with homozygous sickle cell disease (SS group) while 187 (83.11%) were diagnosed with sickle cell trait (AS group). The most common antenatal complications weresickle cell crisis (17; 44.74%) and jaundice (15; 39.47%) in the SS group whereas pregnancy-induced hypertension (PIH) was noted in 33 (17.65%) in the AS group. Intrauterine growth restriction (IUGR) was recorded in 57.89% of the SS group and 21.39% of the AS group. A higher chance of emergency lower segment cesarean section (LSCS; 66.67% in the SS group and 79.09% in the AS group) was recorded as compared with the control group at 32%. In order to minimize risks to the mother and fetus and for better outcomes it is prudent to manage pregnancy with SCDvigilantly in the antenatal period. In the antenatal period mothers with this disease should be screened for hydrops or bleeding manifestations such as intracerebral hemorrhage in the fetus. Better feto-maternal outcomes can be achieved by effective multispecialty intervention.

Dark-Without-Pressure, A Review

Dark-without-pressure fundus lesion (DWP) is a rare, not wellknown entity and its etiology is not yet well understood. It was officially first described in 1975 by Nagpal, et al. [1] in a series of case reports of 7 patients of African origin, 6 having sickle cell haemoglobinopathies and one with arterial hypertension.

Pregnancy in the Sickle Cell Disease and Fetomaternal Outcomes in Different Sickle cell Genotypes: A Systematic Review and Meta-Analysis.

Pregnancy is a major concern among women with the sickle cell disease (SCD), and it is associated with increased adverse outcomes. The aim of the present meta-analysis is to report the fetomaternal outcomes in different sickle cell genotypes. In this systematic review and meta-analysis, a comprehensive search of databases and search engines such as PubMed, Scopus, Web of Science, ProQuest, Cochrane Library, Science Direct and Google Scholar were performed. Any observational studies that had compared at least one outcome such as maternal outcomes, fetal outcomes, and morbidity between two groups of pregnant women with different types of sickle cell genotypes and pregnant women without SCD were evaluated. A total number of 9,827 pregnant women with SCD were examined. The results showed that pregnancy in SCD increased the risk of adverse outcomes for the mothers (including postpartum hemorrhage, prematurity, pregnancy-induced hypertension, pre-eclampsia, eclampsia, cesarean section, lower segment cesareansection, maternal death), fetus (including live births, low birth weight, intrauterine growth restriction, APGAR score at 5 min <7, stillbirth, neonatal death, perinatal mortality, acute fetal distress, intrauterine fetal death) and morbidity among the SCD(severe anemia, urinary tract infection, blood transfusion, painful crisis, acute chest syndrome, vaso-occlusive crises). According to the results of this meta-analysis, pregnancy in the SCD is associated with an increased risk of maternal outcomes, fetal outcomes, and morbidity among SCD patients with different genotypes. Pregnancy in sickle cell hemoglobinopathies needs careful multidisciplinary management and cautious caring so as to decrease maternal and fetal morbidity and mortality.

Demographic and Clinicoradiological Presentation of Tuberculosis in Patients with Sickle Cell Haemoglobinopathy: A Cross-sectional Study

Introduction: Infectious disease is an important contributor to disability and death in Sickle Cell Haemoglobinopathy (SCH). India has a high burden of Tuberculosis (TB) and SCH is widespread among residents in and around Burla, Odisha. This was the first attempt to find the prevalence of SCH in active cases of TB in Indian adults. Aim: To estimate the prevalence of SCH in TB and to evaluate the demographic and clinicoradiological presentation of TB in patients with SCH in a subset of Indian population. Materials and Methods: A cross-sectional study was done from October 2010 to September 2012 in Department of Pulmonary Medicine of V.S.S.M.C, Burla, Odisha, India. The primary inclusion criterion was patients with TB and SCH. Demographic characteristics, clinical, radiological, microbiological and histopathology data were collected. Statistical analysis was done using Statistical Package of the Social Sciences (SPSS) 18.0. Association between categorical data was calculated using Chi-square test and Fischer’s exact test. A p-value of &lt;0.05 was considered to be significant. Results: Out of 1243 TB patients who were screened, 64 TB patients had SCH. The mean age of the patients was 30 (±13) years with female predominance 33 (51.56%). The prevalence of SCH in TB was 51.49/1000, Sickle Cell Anaemia (SCA) was 13.68/1000 and Sickle Cell Trait (SCT) was 37.81/1000. 47 (73.43%) patients had SCT and 17 (26.56%) patients had SCA. Majority of patients with SCA 15 (88.23%) and SCT 35 (74.46%) belonged to the age of ≤40 years. 38 (59.37%) patients had Pulmonary TB (PTB) and 26 (40.62%) had Extrapulmonary TB (EPTB). EPTB 11 (64.70%) was common in patients with SCA than PTB 6 (35.29%) and vice-versa in SCT 15 (31.91% vs 32 (68.08%) (p=0.018). Among PTB patients, cough was the most common symptom seen in 7(10.93%) patients of SCA and in 26 (40.62%) patients of SCT. The mean (±SD) haemoglobin in patients with SCA was 7.270 (±2.007) gm% and SCT was 9.021 (±1.578) gm% (p=0.002). The most common chest radiographic finding was nodules in patients with SCA 9 (52.94%), reticular opacities and pleural effusion 11 (23.40%) each in SCT. Conclusion: In the present study, 5.14% of TB patients had SCH. PTB was more common than EPTB in patients with SCH.

Splenectomy in Sickle Cell Haemoglobinopathies from a Tertiary Hospital of Southern Odisha: A Retrospective Study

Introduction: Sickle Cell Disease (SCD) is a common haemoglobinopathy, where spleen is considered to be the first organ to be involved. Although it initially undergoes enlargement, but most often there occurs autosplenectomy. But in some cases, there is persistence of splenomegaly which may be associated with various complications. In these situations, splenectomy is considered as a good option to mitigate all these morbidities. Aim: To analyse the effect of splenectomy on haematological parameters and complications in patients of SCD in postoperative period. Materials and Methods: This was a retrospective study conducted at SLN Medical College and Hospital, Koraput, Odisha, India, from April 2019 to March 2021. Total 42 patients of SCD underwent splenectomy. The haematological parameters (Haemoglobin (Hb), Total Leucocyte Count (TLC) and Total Platelet Count (TPC)) and blood transfusion needs were compared in pre and postoperative periods and analysed statistically with Student’s t-test. Results: Primary indication of splenectomy was hypersplenism 31 (73.8%) followed by splenic sequestration crisis in 8 patients (19.05%) and splenic abscess in 3 patients (7.1%). Postsplenectomy haemoglobin improvement was around 5.2 gm% (p-value &lt;0.001). Postoperative complication was also minimal, seen in only eight patients, it was mostly due to surgical site infection and fever. Preoperative blood transfusion rate was 9.07±1.92. Blood transfusion requirement rates were also drastically reduced to 0.5±0.707 postsplenectomy in these patients (p-value &lt;0.001). Conclusion: Following splenectomy, the need of blood transfusion was grossly reduced and also, the incidence of its complication was reduced.

P116: THE IMPACT OF COVID19 PANDEMIC ON SICKLE CELL MANAGEMENT: EXPERIENCE OF A SINGLE PEDIATRIC CENTER

Background: COVID19 pandemic has put an incomparable pressure on all health services – including those offered to hemoglobinopathy patients. Sickle cell disease management, although not routinely requiring inpatient facilities, is dependent upon hospital based services on a great extent. Aims: Aim of the present study was to evaluate the impact of COVID19 pandemic on medical management of sickle cell disease patients followed at a single pediatric center in Northern Greece. Methods: Patient records were reviewed in order to assess changes reflecting limited access to specialized care, i.e. number of disease related complications, number of hospital routine visits and number of disease related hospitalizations, during the 18month pandemic in Greece. Results: The study included 23 patients, 17 female (74%) and 6 male (26%). Age range was 2 to 19 years. Eighteen (18) patients (78.3%) were double heterozygotes for sickle cell and beta thalassemia, 4 (17.4%) were sickle cell homozygotes and 1 patient (4.3%) was double heterozygote for sickle cell disease and hemoglobinopathy D. Out of 23 patients, 4 were on regular blood transfusions due disease related issues (primary prophylaxis for cerebrovascular disease or hypersplenism in 2 cases, severe anemia or repeated pain crises in 2 other cases). No significant difference was recorded in number of hospital visits during the 18month period before and during the pandemic (5.45 visits/year and 6 visits/year, respectively – p = 0.49), reflecting a stable course for patients not receiving regular transfusions and an unaffected by blood shortage or limited hospital access course for regularly transfused patients. To that end, no significant changes were recorded in non-COVID related hospitalizations between the two groups (0.57/year before the pandemic and 0.39/year during the pandemic, p = 0.32). In addition, no difference was found between the reported number of pain crises (0.63 episodes per year vs 0.63 episodes per year, p = 1.0). An otherwise unremarkable overall clinical and laboratory course was reported for all patients during the two time periods compared. No changes in regular monitoring was noted and no changes in drug prescription or drug availability for patients on hydroxyurea was recorded. Summary-Conclusions: Although sickle cell patients require close monitoring, mostly dependent upon hospital based services, the COVID19 pandemic does not seem to have limited access to recommended care in this patient group.

Abstract 10271: Correlates and Prognostic Significance of B-Type Natriuretic Peptide in Patients with Sickle Cell Hemoglobinopathies

Introduction: Natriuretic peptides (NP) are hormones released from the heart in response to cardiac stress. Sickle cell hemoglobinopathies are conditions with increased cardiovascular stress, yet few studies have examined determinants of and the relative prognostic significance of NP levels in these patients. Hypothesis: We assessed the hypothesis that plasma B-type NP (BNP) level is one of the strongest independent predictors of death among patients with sickle cell hemoglobinopathies. Methods: From the Vanderbilt University Medical Center electronic health record, we retrospectively studied adult patients with sickle cell disease (SCD, n = 278; median age 30 years, 50% female) and sickle trait (ST, n = 196; median age 45 years, 73% female) in whom BNP was clinically measured from 2003-2020. The association between BNP and risk of death was assessed with multivariable Cox regression. Correlates of BNP levels were examined in multivariable ordinal logistic regression. Results: Over 1846 person-years of follow-up, 43 (9%) patients died. BNP, age, and lactate dehydrogenase levels were the three strongest predictors of death, accounting for 29%, 18%, and 13% of the explained variance in the risk of death, respectively. Each 110 pg/ml greater BNP was associated with a 5% (95% CI: 4-6%) increased risk of death. SCD was associated with a 19% (95% CI: 5 to 36%) increased risk of death compared to ST. Among patients with SCD, significant correlates of BNP ranked by strength of association were hemoglobin, white blood cell count, age, pulmonary artery systolic pressure (PASP), hypertension, left ventricular ejection fraction (LVEF), and neutrophil count (Figure). For patients with ST, the strongest correlates of BNP were PASP, hemoglobin, stroke, age, diabetes, and LVEF. Conclusions: In conclusion, BNP is the strongest predictor of death independent of anemia severity and other features of cardiac structure and function among patients with sickle cell hemoglobinopathies.

SCREENING OF FUNGI FOR PRODUCTION AND PURIFICATION OF OMEGA-3 FATTYACID

Sickle cell hemoglobinopathy patients are vexed with sickle cell crises crises all through their life. Occurrence of jaundice in these patients is quite common and when present gets ascribed to the sickle cell crisis, sickle cell hepatopathy, intrahepatic cholestasis or cholelithisis. Further, incidence of viral hepatitis is extremely common in these patients. Clinically it is difficult to distinguish this aetiology. We have attempted to identify the criteria to help differentiate amongst sicklers which patients should be investigated for viral hepatitis. Also, sicklers with hepatitis have been studied against non sicklers with hepatitis and also complications of hepatitis in these two groups.

Iron profile of pregnant sickle cell anemia patients in Odisha, India

IntroductionDuring pregnancy, the iron requirement increases to meet the optimal growth of the fetus and prevent iron deficiency anemia-related complications in the mother. However, in sickle cell disease (SCD) primarily due to repeated blood transfusions and hemolysis-induced recycling of iron, its supplementation during pregnancy remains questionable and may be harmful. MethodsTwenty-five pregnant women with homozygous SCD and 25 pregnant women with normal hemoglobin variants were included as cases and control, respectively. Pregnancy and sickle cell anemia (SCA) were diagnosed using standard protocols. The serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and C-reactive protein were estimated, as per the manufacturer's protocol. The complete blood count was performed. The unpaired ‘t-test’ was performed using the SPSS v23.0 and the principal component analysis (PCA) was performed using the online software MetaboAnalyst for statistical analysis. Main ResultsThe studied cases had significantly lower mean hemoglobin and higher mean corpuscular volume (MCV), compared to controls. The mean serum-iron, serum-ferritin and percentage transferrin-saturation in the cases were significantly higher than that of the controls, while the TIBC was lower in the cases (p < 0.0001). The mean level of serum iron, ferritin, percentage transferrin saturation and TIBC were 309.44 ± 122.40mcg/dl, 860.36 ± 624.64ng/ml, 42.6 ± 17.30% and 241.32 ± 96.30 mcg/dl, respectively, in the cases and 95.36 ± 41.90mcg/dl, 122.28 ± 49.70ng/ml, 15.83 ± 3.10% and 492.6 ± 149.40mcg/dl in the controls, respectively. Higher MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with lower hemoglobin (Hb) were noted in the cases. The PCA revealed that the cases were more heterogeneous in terms of the variability of the iron status and hematological indices than the controls. ConclusionThe current study shows iron sufficiency in most cases of pregnancy with SCA and suggests that evaluation of iron status must be made before initiating iron prophylaxis in pregnant women with SCA, especially in regions having a high prevalence of sickle cell hemoglobinopathy.

Safety of 3 Tesla Magnetic Resonance Imaging in Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a well-characterized hemoglobinopathy affecting more than 20 million individuals worldwide and carries an increased risk of cerebral vasculopathy, cerebral infarct, and stroke. As mechanisms of cerebral infarction in SCD are partly attributable to microvascular vaso-occlusive crises, manifesting as altered cerebral blood flow and associated impaired oxygen delivery, magnetic resonance imaging (MRI) methods that can quickly provide a comprehensive perspective on structural and functional disease status, without exogenous contrast administration or ionizing radiation, have emerged as crucial clinical tools for surveillance. However, early ex vivo MRI work in suspended erythrocytes containing hemoglobin S at 0.35 Tesla (T) suggested that sickled erythrocytes can orient preferentially in the presence of an external magnetic field, and as such, it was suggested that MRI exams in sickle cell hemoglobinopathy could induce vaso-occlusion. While this observation has generally not impacted clinical imaging in individuals with SCD, it has led to resistance for some sickle cell studies within the engineering community among some imaging scientists as this early observation has never been rigorously shown to be unconcerning. Here, we performed MRI at the clinical field strength of 3 T in 172 patients with SCD, which included standard anatomical and angiographic assessments together with gold standard diffusion-weighted imaging (DWI; spatial resolution = 1.8 × 1.8 × 4 mm; b-value = 1000 s/mm2) for acute infarct assessment (performed approximately 20 min after patient introduction to the field isocenter). The presence of vasculopathy, as well as chronic and acute infarcts, was evaluated by two independent board-certified radiologists using standard clinical criteria. In these patients (52.3% female; mean age = 19.6 years; age range = 6–44 years), hematocrit (mean = 25.8%; range = 15–36%), hemoglobin phenotype (87.8% HbSS variant), presence of silent infarct (44.2%), and overt chronic infarct (13.4%) were consistent with a typical SCD population; however, no participants exhibited evidence of acute infarction. These findings are consistent with 3 T MRI not inducing acute infarction or vaso-occlusion in individuals with SCD and suggest that earlier low-field ex vivo work of erythrocytes in suspension is not a sufficient cause to discourage MRI scans in patients with SCD.

Deep Learning Detection of Sea Fan Neovascularization From Ultra-Widefield Color Fundus Photographs of Patients With Sickle Cell Hemoglobinopathy

Adherence to screening for vision-threatening proliferative sickle cell retinopathy is limited among patients with sickle cell hemoglobinopathy despite guidelines recommending dilated fundus examinations beginning in childhood. An automated algorithm for detecting sea fan neovascularization from ultra-widefield color fundus photographs could expand access to rapid retinal evaluations to identify patients at risk of vision loss from proliferative sickle cell retinopathy. To develop a deep learning system for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy. In a cross-sectional study conducted at a single-institution, tertiary academic referral center, deidentified, retrospectively collected, ultra-widefield color fundus photographs from 190 adults with sickle cell hemoglobinopathy were independently graded by 2 masked retinal specialists for presence or absence of sea fan neovascularization. A third masked retinal specialist regraded images with discordant or indeterminate grades. Consensus retinal specialist reference standard grades were used to train a convolutional neural network to classify images for presence or absence of sea fan neovascularization. Participants included nondiabetic adults with sickle cell hemoglobinopathy receiving care from a Wilmer Eye Institute retinal specialist; the patients had received no previous laser or surgical treatment for sickle cell retinopathy and underwent imaging with ultra-widefield color fundus photographs between January 1, 2012, and January 30, 2019. Deidentified ultra-widefield color fundus photographs were retrospectively collected. Sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network for sea fan detection. A total of 1182 images from 190 patients were included. Of the 190 patients, 101 were women (53.2%), and the mean (SD) age at baseline was 36.2 (12.3) years; 119 patients (62.6%) had hemoglobin SS disease and 46 (24.2%) had hemoglobin SC disease. One hundred seventy-nine patients (94.2%) were of Black or African descent. Images with sea fan neovascularization were obtained in 57 patients (30.0%). The convolutional neural network had an area under the curve of 0.988 (95% CI, 0.969-0.999), with sensitivity of 97.4% (95% CI, 86.5%-99.9%) and specificity of 97.0% (95% CI, 93.5%-98.9%) for detecting sea fan neovascularization from ultra-widefield color fundus photographs. This study reports an automated system with high sensitivity and specificity for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy, with potential applications for improving screening for vision-threatening proliferative sickle cell retinopathy.

Frequency distribution of the methylenetetrahydrofolate reductase polymorphisms in sickle cell hemoglobinopathy-A hospital based study in central India

BackgroundCoexistence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) with sickle cell gene exerts synergistic effect on complications associated with sickle cell hemoglobinopathy. Therefore, the study was planned to determine the frequency distribution of the MTHFR C677T and A1298C genotypes in children diagnosed with sickle cell disease. MethodsA total of 249 children diagnosed with sickle cell anemia, between age group 5–18 years, were enrolled for the cross sectional study. The demographic and clinical details were entered in a structured questionnaire. Collected blood samples were analyzed for hemoglobin and DNA was extracted for genotypic assay for MTHFR C677T and A1298C single nucleotide polymorphisms (SNPs) by Real-time PCR. ResultsThe study groups comprised of 218 sickle cell trait (SCT) and 31 sickle cell disease (SCD) children. The caste distribution between the two study groups was quite uniform (X231 = 44.21, p = 0.06). Frequencies of homozygous mutants 677TT and 1298CC were 2% and 19.7% respectively. The odds for the variant forms for both SNPs were found to be greater in SCD group. The genotypic and allelic frequencies did not reveal any caste preponderance. The mean age (p = 0.001), weight (p < 0.001), height (p < 0.001), BMI (p < 0.001) and hemoglobin concentrations (p = 0.002) were lower in homozygous 1298CC but not so in 677TT children. A1298C also depicted significant association with BMI and anemia (p < 0.001). ConclusionHomozygous mutant MTHFR variants would be essential genetic markers especially in children with SCD to identify the vulnerable group who frequently get hospitalized for vascular complications.

Surgical Site Infection Caused by Salmonella Enteritidis in a Patient With Meningioma

Abstract Salmonella is known to cause gastrointestinal illness globally. Primarily being an enteric pathogen, other extraintestinal infections are often obscured by gastrointestinal disease. However, Salmonella has also been reported to cause wound infections, endovascular infections, pneumonia, abscess, and osteomyelitis. These are more commonly encountered in immunocompromised patients, especially in developing countries. The authors report a case of surgical-site infection caused by Salmonella in a patient with meningioma. Salmonella causes only less than 1% of infections involving bones and joints and is more commonly reported from patients with sickle-cell hemoglobinopathy or autoimmune disorders such as systemic lupus erythematosus. Our patient had no such risk factors. This report highlights the unusual presentation of Salmonella infection in a diabetic patient, which further complicated the ongoing illness, thereby increasing the morbidity.

Vulnerable Child Syndrome and Newborn Screening Carrier Results for Cystic Fibrosis or Sickle Cell

To measure parental perceptions of child vulnerability, as a precursor to developing a population-scale mechanism to mitigate harm after newborn screening. Participants were parents of infants aged 2-5months. Parental perceptions of child vulnerability were assessed with an adapted version of the Vulnerable Baby Scale. The scale was included in the script for a largerstudy of telephone follow-up for 2 newborn blood screening samples (carrier status for cystic fibrosis or sicklecell hemoglobinopathy). A comparison sample was added using a paper survey with well-baby visits to an urban/suburban clinic. Sample sizes consisted of 288 parents in the cystic fibrosis group, 426 in the sickle cell hemoglobinopathy group, and 79 in the clinic comparison group. Parental perceptions of child vulnerability were higher in the sickle cellgroup than cystic fibrosis group (P<.0001), and both were higher than the clinic comparison group (P<.0001). Parental perceptions of child vulnerability were inversely correlated with parental age (P<.002) and lower health literacy (P<.015, sickle cell hemoglobinopathy group only). Increased parental perceptions of child vulnerability seem to be a bona fide complication of incidental newborn blood screening findings, and healthcare professionals should be alert to the possibility. From a public health perspective, we recommend routine follow-up after incidental findings to mitigate psychosocial harm.

Abstract 4815: Differential expression profiling of long noncoding RNA establishes UCA1 as a hallmark of renal medullary carcinoma

Abstract Renal medullary carcinoma (RMC) is a rare but highly lethal renal cell carcinoma (RCC) that predominantly afflicts young African Americans with sickle cell hemoglobinopathies. There are currently no approved targeted therapies for RMC and the median survival from diagnosis is 13 months despite best available treatments. New biomarkers and therapeutic targets are therefore urgently needed for this very aggressive disease. No studies to date have profiled the long noncoding RNA landscape of RMC. We performed RNA sequencing in untreated primary tumor samples obtained from 11 patients with RMC. The lncRNA expression profile of RMC was compared to that of adjacent normal kidney (n = 6 patients with RMC), upper tract urothelial carcinoma (UTUC), and closely related RCCs including collecting duct carcinoma (CDC), clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (chRCC). We performed principal component analyses as well as hierarchical clustering of the lncRNA expression levels using the Pearson correlation coefficient as the distance metric and the ward's linkage rule. The read counts of each lncRNA were fitted using a negative binomial model and a Wald test was used in DESeq2 to compare expression levels. The false discovery rate (FDR) was controlled using the Benjamini and Hochberg method. We found that the lncRNA signature of RMC is clearly distinct from that of ccRCC, pRCC, and chRCC, but substantially overlaps with CDC. Urothelial cancer associated 1 (UCA1) was the highest upregulated lncRNA (305-fold increase, FDR &amp;lt; 0.001) in RMC compared with adjacent normal kidney. This dramatic upregulation of UCA1 was similar to that seen in UTUC and not found in any of the other RCCs, including CDC. UCA1 is known to be associated with chemotherapy resistance and was previously considered to be highly specific for urothelial carcinoma. Our findings now suggest that UCA1 is also a hallmark of RMC. Future studies will focus on elucidating the functional consequences of UCA1 expression in RMC pathobiology. Citation Format: Pavlos Msaouel, Gabriel G. Malouf, Xiaoping Su, Hui Yao, Durga N. Tripathi, Jianjun Gao, Priya Rao, Jean-Philippe Bertocchio, Jose Karam, Christopher G. Wood, Cheryl L. Walker, Giannicola Genovese, Nizar M. Tannir. Differential expression profiling of long noncoding RNA establishes UCA1 as a hallmark of renal medullary carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4815.

Ocular Manifestations of Sickle Cell Disease in Different Genotypes

ABSTRACT Background Sickle cell disease (SCD) is a multisystemic disorder with variable systemic involvement which varies according to genotype. In this study, our aim is to compare ocular complications between HbSS, HbSC, HbS/β+ thalassemia, HbS/β0 thalassemia, SS alpha thalassemia, and S/β0 + alpha thalassemia genotypes. Methods Data of patients included in this study was recruited from the Cooperative Study of Sickle Cell Disease (CSSCD). Patients with major sickle cell hemoglobinopathies (SS, SC, Sβ- thalassemia, SS alpha thalassemia) were eligible for enrollment, after that, a detailed eye exam was performed. We categorized ocular complications into conjunctival sign, iris atrophy, and both proliferative and non-proliferative sickle cell retinopathy. Results A total of 1867 patients were included in this study, with a mean age of 27.7 (± 11.7) years. They were 830 (44.5%) males and 1037 (55.5%) females. The most common genotype was SS with 971 (52%) patients, and the least common form was sickle cell with both alpha and beta thalassemia major with 42 (2.2%) patients. We found a significant difference in the frequency of proliferative sickle cell retinopathy, where SC genotype had the highest frequency and S B0 thalassemia genotype had the lowest frequency. We also found a significant difference in the frequency of conjunctival sign, where SS genotype had the highest frequency and the S B+ thalassemia has the lowest frequency. Conclusion We identified ocular complications for major sickle cell hemoglobinopathies, where we confirmed previous small study’s findings and identified ocular complications of less common hemoglobinopathies.

Knowledge, awareness, and attitude of premarital screening with special focus on sickle cell disease: a study from Odisha.

Sickle cell disease (SCD) is a genetic disorder with an estimated 5200 live births each year indicating towards a major public health issue in India. Although SCD has been described in India in numerous ethnic groups, it is most prevalent in tribal community. Prevalence of sickle cell gene is 5 to 34% in tribal communities, who have a high prevalence of socioeconomic disadvantage and are frequently medically underserved. The objective of the present study is to explore the knowledge, awareness, and attitude of premarital genetic counseling and screening for sickle cell hemoglobin among individuals of Koraput district. A cross-sectional study design was employed and a total of 152 individuals were recruited using multistage sampling technique, including 43 individuals with sickle cell hemoglobinopathy. Data was collected using a pre-tested, self-administered questionnaire and analyzed using SPSS-20. Though people are aware of SCD and SCT, majority believe that sickle cell carriers transmit the disease and they do not know that marriage between sickle cell carriers need to be avoided.