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Adi Finkelstein,1,* Elisheva Leiter,2,* Tanya Reinfeld,2 Ora Levy,2 Sara Hoss,2 Lori Sloman,2 Donna R Zwas2 1Department of Nursing, Faculty of Life and Health Sciences, Jerusalem College of Technology, Jerusalem, Israel; 2Linda Joy Pollin Cardiovascular Wellness Center for Women, Hadassah University Medical Center, Jerusalem, Israel*These authors contributed equally to this workCorrespondence: Elisheva Leiter, Linda Joy Pollin Cardiovascular Wellness Center for Women, Cardiology Department, Hadassah University Medical Center Ein Karem, POB 12000, Jerusalem, 91120, Israel, Tel +1 972 54 332 9044, Email elisheval@hadassah.org.ilPurpose: Cardiovascular disease in women is frequently under-diagnosed and under-treated. Numerous heart centers for women have opened throughout the world to address these disparities; however, there is a paucity of data regarding participants’ perspectives. The current study assesses motivation to participate and perceived benefits in attending a heart center for women (HCW) in Jerusalem, Israel.Methods: This study utilized qualitative methods to assess patients’ motivation and perceived benefits to attending a women’s heart center, particularly as they relate to gender medicine and single-sex staffing. A random sample of 42 clinic patients were asked to participate in interviews. Inclusionary criteria consisted of previous cardiovascular event, active cardiac symptom or three or more cardiovascular disease risk factors. Exclusionary criteria consisted of pregnancy, type 1 diabetes requiring insulin, psychiatric diagnosis that precluded participation, dementia, or other multidisciplinary clinic participation. Interviews were audio recorded and transcribed verbatim. Qualitative data analysis followed Braun and Clarke’s methodology of thematic analysis.Results: The single-sex and gender medicine aspects did not motivate women to attend the HCW, although some participants perceived this as beneficial in retrospect. Women reported that the clinic visit enhanced their knowledge and awareness of issues related to heart disease in women as well as personal health benefits. They reported benefitting from the holistic approach, consideration of their lifestyle, the staff’s expression of concern, personalized attention, common language, and feeling understood.Conclusion: This study describes the patient experience in an all-female HCW, highlighting their motivation for attendance and perceived benefits. While they did not actively seek women-centered care, women reported educational and care provision benefits to their attendance. The care attributes that women identified as beneficial typify the person-centered approach to care. These findings may inform both the design and evaluation of medical care facilities that aim to address the sex and gender disparities in cardiology as well as other medical specialties.Keywords: gender medicine, patient experience, cardiovascular disease, person-centered care

Quantity and quality of dissolved organic matter (DOM) and the time allowed for DOM to interact with organic contaminants can influence their bioavailability. We studied the effect of natural aquatic DOM that had been in contact with benzo[a]pyrene (B[a]P) for 1 to 12 d on the bioconcentration of B[a]P in the nematode Caenorhabditis elegans. Dissolved organic matter quality and quantity was varied by using DOMfrom three different sources, each in three concentrations. A model,based on the assumption that only freely dissolved B[a]P is bioavailable, was employed to estimate 'biologically determined' partition coefficients [Kp(biol.)]. Expressing the data for each combination of DOM source and contact time in a single Kp(biol.) value allowed a direct comparison of the effects of different DOM qualities and contact times. Our results show that the effect of DOM from a specific source was dependent on DOM quantity, but we also observed a distinct effect of DOM quality (represented by different sampling locations) on the bioconcentration of B[a]P. Contact time had no significant influence for the effects of two DOM sources on the bioconcentration of B[a]P. However, the third DOM source was significantlymore effective with increased contact time, leading to lower B[a]P bioconcentration in the nematodes. [ABSTRACT FROM AUTHOR]

We present a method using the free-living nematode Caenorhabditis elegans (Maupas, 1899) to assess toxicity in liquid medium and whole-sediment setups. Test duration is 72 h; endpoints are body length, number of eggs inside worms, percentage of gravid worms, and number of offspring per worm. The effect of CdCl{sub}2{end} on C. elegans in liquid-phase exposures is described as an example. Results from a field study with polluted sediments from the River Elbe (Germany) suggest that nematodes may be useful organisms in assessing toxicity of sediments in the whole phase. [ABSTRACT FROM AUTHOR]

The aim of this study is to describe general features of sediment, primary producers and both benthic and planktonic consumers in two shallow saline lakes (Salada de La Muerte and Salada de Piqol) in order to detect main factors influencing food web structure. The lakes arelocated in Los Monegros district, in the central area of the Ebro River catchment, NE Spain. Both lakes are temporary with salinity well above 30 g L-1. Although they are situated close to each other (distance: 300 m), their communities of primary producers differdramatically. One lake (La Muerte) is dominated by microbial mats and seems to function through the benthic pathway. The other (Piqol) has some macrophytes but phytoplankton is the main source of primary production. Two cycles (1994/95 and 1995/1996), quite different in their hydrological characteristics, have been studied. PCA demonstrated the major influence of hydrologic features (e.g. water level) over biotic and abiotic parameters. The presence of microbial mats in La Muerte played a key role in stabilizing the sediments. A comparison of food web structure and dynamics in both lakes has been performed and the influence of sediment features is discussed. [ABSTRACT FROM AUTHOR]

This commentary discusses the therapeutic potential of drug repurposing in sickle cell disease, highlighting the efficacy of hydroxyurea in enhancing fetal haemoglobin and the work of Raz et al. discussing the potential of using memantine for improving cognitive function, while emphasizing the need for further research. Commentary on: Raz et al. Memantine treatment in sickle cell disease: A 1-year study of its effects on cognitive functions and neural processing. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19866., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused β-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underestimated biological problem with potential clinical consequences in sub-Saharan Africa., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: There is limited data regarding the impact of exercise on phenotypic expression in hypertrophic cardiomyopathy (HCM). We aimed to investigate whether such an association exists in a cohort of genotype-positive HCM patients., Methods: In this cross-sectional study of genotype-positive HCM families, we used structured questionnaires to obtain data regarding intensity and duration of exercise of participants starting at the age of 10, as well as data regarding exercise recommendations and their impact on quality of life (QOL). The association of cumulative metabolic-equivalent hours of exercise at different ages with different measures of phenotypic expression (maximal wall thickness, left atrial diameter, extent of late gadolinium enhancement) was analyzed., Results: The study included 109 patients from 55 families, including 43 male (39%) and 90 (83%) phenotype-positive. No association was identified between exercise duration or intensity with any of the phenotypic markers with the exception of greater cumulative exercise associated with younger age at presentation. Similar results were obtained when analysis was limited to exercise until the age of 20, until the age of 30 or only after 30. Among phenotype-positive patients, 89% recalled receiving recommendations regarding exercise restriction, 29% noted reduction in exercise level following such recommendations and 25% noted this having a significant impact on their QOL., Conclusion: We found no association between exercise intensity or duration and phenotypic expression in genotype-positive HCM patients. These findings are important for physician-patient discussions and support the recent trend towards more permissive exercise restrictions in HCM., Competing Interests: Declaration of Competing Interest Dr. Adler is a consultant for Britsol-Myers-Squib, which did not participate in this study. The other authors report no conflicts., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The optimal management of hypertrophic cardiomyopathy (HCM) patients with postoperative atrial fibrillation (POAF) after surgical myectomy remains unknown. We sought to investigate the association between POAF and atrial fibrillation (AF) or cardioembolic events during follow-up to bridge this gap., Methods: Patients undergoing surgical myectomy at 2 HCM referral centres in North America from 2002 to 2020 were included in this study. Patients with preoperative AF were excluded. POAF was defined as any episode of AF within 30 days after surgery., Results: Of 1176 patients, 375 (31.9%) had POAF. Age (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P < 0.001), premyectomy left atrial diameter (LAD; adjusted HR 1.6, 95% CI 1.32-2.02; P < 0.001), and smoking (adjusted HR 1.60, 95% CI 1.17-2.20; P = 0.001) were associated with POAF on multivariable analysis. Of 934 patients with follow-up data, of duration 4.3 ± 4.1 years, AF was detected in 86 (9.2%). Only POAF (HR 4.20, 95% CI 2.44-7.23; P < 0.001), previous history of stroke (HR 4.81, 95% CI 1.63-14.17; P = 0.01), and postmyectomy LAD (HR 1.80, 95% CI 1.21-2.70; P = 0.004) were associated with AF incidence during follow-up. Cardioembolic events occurred in only 15 patients (1.6%). POAF was not associated with increased cardioembolic risk, with only 3 patients with POAF suffering such an event, all more than 4 years after surgery., Conclusions: POAF is common in HCM patients undergoing myectomy and is a predictor of AF during follow-up. Over long-term follow-up, cardioembolic events are uncommon. These findings suggest that routine long-term anticoagulation for all HCM patients with postmyectomy AF is not justified after the initial postoperative period., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures None.

Background: Left ventricular (LV) apical aneurysms in hypertrophic cardiomyopathy (HCM) are a recognized risk marker for adverse cardiovascular events. There is variable practice among clinicians and discordance between international guidelines regarding treatment recommendations and prognostication for this important phenotype., Objectives: The authors sought to describe the morphology, clinical course, and risk of adverse events in a large single-center cohort of HCM patients with LV apical aneurysms., Methods: This study analyzed 160 HCM patients with an LV apical aneurysm who were evaluated in our dedicated HCM clinic between January 1997 and April 2021., Results: Mean age was 59.1 ± 13.6 years, and 71% of these patients were male. Mean aneurysm size was 1.77 ± 1.04 cm. Over 6.2 ± 4.8 years, 14 (9%) patients had a sudden cardiac death (SCD) event, including appropriate therapy from an implantable cardioverter-defibrillator (ICD) or resuscitation from cardiac arrest (annualized event rate 1.77%/y), 39 (24%) had either a thromboembolic stroke or apical thrombus formation (2.9%/y), and 14 (9%) developed LV systolic dysfunction with an ejection fraction (EF) <50% (1.28%/y). HRs for SCD, stroke or thrombus, and EF <50% per 1-cm increase in aneurysm size were 1.69 (P = 0.007), 1.60 (P = 0.0002), and 1.63 (P = 0.01), respectively. Aneurysm size ≥2 cm was associated with a 5-year SCD rate of 9.7%, compared with 2.9% for aneurysm size <2 cm (log-rank P = 0.037). This subgroup also had higher risk of stroke/thrombus formation (HR: 2.20; P = 0.002), with an annualized event rate of 2.7%/year. A total of 39 (24%) patients reached the combined end point of SCD, stroke, or LV dysfunction (2.12%/y) with an HR of 1.47/cm increase in aneurysm size (P = 0.003) and an HR of 2.22 for patients with aneurysm size ≥2 cm (P = 0.02)., Conclusions: Increasing aneurysm size confers poorer prognosis. Aneurysm size ≥2 cm should alert potential consideration for prophylactic anticoagulation and primary prevention ICDs., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

α-Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12-year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α-thalassemia strongly reduces erythrocyte potassium chloride co-transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α-thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α-thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno-protective effect of α-thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10 -10 ). We found patients with α-thalassemia had a reduced annualized transfusion burden in both HbSS and HbSC, but α-thalassemia had no impact on annualized admission rates in either group. Finally, in a larger cohort, we report a median survival of 62 years in patients with HbSS (n = 899) and 80 years in those with HbSC (n = 240). α-thalassemia did not influence survival in HbSS, but a nonsignificant trend was seen in those with HbSC., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Sickle cell disease (SCD) is characterized by variable clinical outcomes, with some patients suffering life-threatening complications during childhood, and others living relatively symptom-free into old age. Because of this variability, there is an important potential role for precision medicine, in which particular different treatments are selected for different groups of patients. However, the application of precision medicine in SCD is limited by difficulties in identifying different prognostic groups and the small number of available treatments. The main genetic determinant of outcomes in SCD is the underlying β-globin genotype, with sickle cell anemia (HbSS) and hemoglobin SC disease (HbSC) forming the 2 major forms of the disease in most populations of African origin. Although there are clear differences in clinical outcomes between these conditions, treatments approaches are very similar, with little evidence on how to treat HbSC in particular. Other genomic information, such as the co-inheritance of α-thalassemia, or high fetal hemoglobin (HbF) levels, is of some prognostic value but insufficient to determine treatments. Precision medicine is further limited by the fact that the 2 main drugs used in SCD, penicillin and hydroxyurea, are currently recommended for all patients. Newer treatments, such as crizanlizumab and voxelotor, raise the possibility that groups will emerge who respond best to particular drugs or combinations. Perhaps the best current example of precision medicine in SCD is the selective use of blood transfusions as primary stroke prevention in children with evidence of cerebral vasculopathy. More precise treatments may emerge as we understand more about the pathology of SCD, including problems with erythropoiesis., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8 ± 2.1 years. Progression of indexed left ventricular mass (LVMI) was correlated with lower LVMI at baseline (p <0.00001) and older age >50 years. In terms of maximal wall thickness (MWT), progression was associated with lower baseline MWT and with the presence of LV outflow tract obstruction. No association was demonstrated between the degree of progression of LVMI or MWT and baseline LV volumes, the severity of mitral regurgitation, gender, or the presence of pathogenic HC variants. Progression of left atrial size was significantly associated with the development of atrial fibrillation (p = 0.014; odds ratio 1.18, confidence interval 1.03 to 1.35) and admission for heart failure (p = 0.018; odds ratio 1.18, confidence interval 1.03 to 1.36). No correlation was demonstrated between changes in LV mass or MWT and clinical outcomes of admission for heart failure, progression to New York Heart Association 2/3, progression to end-stage HC, or implantable cardioverter-defibrillator implantation. In conclusion, our study provides novel insights into the natural history of HC from a morphological perspective. It shows that HC is a dynamic disease in which LV morphology and hypertrophy extent change over time, with the presence of risk factors associated with disease progression., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Attachment parameters affect the development of self-concept and relationship patterns. However, studies on the impact of attachment parameters on symptoms of the offspring in childhood are still lacking. We therefore investigated the influence of attachment parameters of the grandparents on those of the parents treated in a psychiatric hospital, and finally on the symptoms of their (grand)children. Furthermore, the impact of attachment factors on parenting style and on resilience of parents and children has been examined., Subjects and Methods: A sample of n=50 mother-child-dyads in an inpatient setting was examined using the questionnaires FEB (Questionnaire on the Parental Attachment; adult and child perspective), RQ2 (Relationship Questionnaire), EFB-K (Educational Questionnaire, short form), RS13 (Resilience Scale; adult and child perspective), and CBCL (Child Behavior Checklist). Regression analyses and correlation analyses were carried out., Results: On grandparents' level, attachment patterns predicted parents' attachment patterns (p=0.012): Grandfather's care (control) behavior correlated with more (less) mother's care for their own children (0.002 (0.005)). Control behavior of the grandfather was negatively correlated with the resilience of their daughters (p=0.033). On parents' level, a secure attachment style predicted a less overreacting parenting style (p=0.004), whereas an anxious-avoiding (p=0.035) or clinging attachment style (p=0.044) predicted an increased overreacting parenting style. On child's level, mental (esp. attentional (p=0.013) and externalizing (p=0.032)) symptoms correlated negatively with the level of care reported by the mother., Conclusion: Functional attachment behavior at the grandparents' level correlated significantly with functional attachment behavior at the parental level, which in turn correlated with reduced mental symptoms at the child's level. The parenting style seems to play a mediator role for the development of attachment between mother and child, with resilience mediating between attachment and the onset of mental disorders. The results point to the crucial role of attachment parameters for mental development with corresponding implications for psychotherapy.

Background: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored., Methods: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose., Results: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function., Conclusions: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Left ventricular (LV) apical aneurysm is a unique morphological entity and novel adverse risk marker existing within the broad phenotypic spectrum of hypertrophic cardiomyopathy (HCM). Its true prevalence in the HCM population is likely underestimated because of inherent limitations of conventional noncontrast echocardiography. The authors hypothesized that contrast echocardiography is a reliable imaging technique compared with cardiovascular magnetic resonance (CMR) for the detection of apical aneurysms. The aim of this study was to assess the effectiveness of contrast echocardiography in the detection of LV apical aneurysms in patients with HCM in comparison with the gold standard, CMR., Methods: One hundred twelve patients with HCM identified from an institutional clinical database, who underwent echocardiographic and CMR examinations within 12 months and had LV apical aneurysms identified on either or both imaging modalities, were retrospectively analyzed. Discordant cases were reviewed by an expert panel, and a consensus was reached regarding the presence or absence of an apical aneurysm. The reason for any discrepancy was recorded., Results: The mean age of the patients was 59 ± 13 years, and 73% were men. Sixty-four (57%) underwent contrast echocardiography. The median interval between echocardiography and CMR was 118 days (interquartile range, 61-237 days). Thirty-nine patients (35%) had discordance between echocardiographic and CMR findings, of whom 20 had aneurysms reported on echocardiography but not CMR and 19 vice versa. Upon reanalysis by the expert panel, aneurysms were initially missed on CMR in 16 patients (80%), largely because of interpretation error secondary to small aneurysms, with a mean aneurysm size of 0.82 ± 0.38 cm in these cases. Before secondary review by the expert panel, contrast echocardiography had sensitivity of 97% compared with 85% for CMR (P = .0198) and 64% for noncontrast echocardiography (P = .0001). After secondary review, contrast echocardiography had sensitivity of 98% compared with 67% for noncontrast echocardiography (P = .0001) and 97% for CMR (P = 1.00)., Conclusions: Contrast echocardiography has high sensitivity for detecting LV apical aneurysms and should be used routinely in the evaluation and risk stratification of patients with HCM., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

While ineffective erythropoiesis has long been recognized as a key contributor to anemia in thalassemia, its role in anemia of sickle cell disease (SCD) has not been critically explored. Using in vitro and in vivo derived human erythroblasts we assessed the extent of ineffective erythropoiesis in SCD. Modeling the bone marrow hypoxic environment, we found that hypoxia induces death of sickle erythroblasts starting at the polychromatic stage, positively selecting cells with high levels of fetal hemoglobin (HbF). Cell death was associated with cytoplasmic sequestration of heat shock protein 70 and was rescued by induction of HbF synthesis. Importantly, we document that in the bone marrow of SCD patients similar cell loss occurs during the final stages of terminal differentiation. Our study provides evidence for ineffective erythropoiesis in SCD and highlights an anti-apoptotic role for HbF during the terminal stages of erythroid differentiation. These findings imply that the beneficial effect on anemia of increased HbF levels is not only due to the increased life span of red cells but also a consequence of decreased ineffective erythropoiesis.

Vaso-occlusive crises are the hallmark of sickle cell disease (SCD). They are believed to occur in two steps, starting with adhesion of deformable low-dense red blood cells (RBCs), or other blood cells such as neutrophils, to the wall of post-capillary venules, followed by trapping of the denser RBCs or leukocytes in the areas of adhesion because of reduced effective lumen-diameter. In SCD, RBCs are heterogeneous in terms of density, shape, deformability and surface proteins, which accounts for the differences observed in their adhesion and resistance to shear stress. Sickle RBCs exhibit abnormal adhesion to laminin mediated by Lu/BCAM protein at their surface. This adhesion is triggered by Lu/BCAM phosphorylation in reticulocytes but such phosphorylation does not occur in mature dense RBCs despite firm adhesion to laminin. In this study, we investigated the adhesive properties of sickle RBC subpopulations and addressed the molecular mechanism responsible for the increased adhesion of dense RBCs to laminin in the absence of Lu/BCAM phosphorylation. We provide evidence for the implication of oxidative stress in post-translational modifications of Lu/BCAM that impact its distribution and cis-interaction with glycophorin C at the cell surface activating its adhesive function in sickle dense RBCs.