Effect of hydroxyurea exposure before puberty on sperm parameters in males with sickle cell disease.

Sperm parameters are known to be impaired in men with sickle cell disease (SCD). Although treatment with hydroxyurea (HU) has an impact on sperm quality, sperm preservation is impossible before puberty. This study's primary objective was to analyze and compare sperm parameters in male patients with SCD exposed (or not) to HU before puberty. Twenty-six sperm samples from 15 patients (median age, 17 years; range, 16-23) treated with HU during childhood were compared with 46 samples from 23 HU-naïve patients (20 years; 16-24). The median age at HU initiation was 6 years (1-14 years), the median duration of HU treatment was 4 years (0.5-10), and the mean dose of HU was 22.4 ± 3.7 mg/kg per day. Although we observed substantial quantitative and qualitative semen abnormalities in all patients, there were no significant differences in semen volume, sperm concentration, total sperm count, or spermatozoa motility, morphology, and vitality between the HU-exposed and HU-naïve groups. At the time of the semen analysis, 100% of the patients in the HU-exposed group and 52% of the patients in the HU-naïve group received transfusion therapy. The specific effect of HU on spermatogenesis in very young infants and the putative value of transfusion for reversing the toxicity of HU warrant further investigation.

Astaxanthin effectiveness in preventing multiple sclerosis in animal model.

OBJECTIVE: The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS). BACKGROUND: Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers. METHODS: The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG). Splenocytes were assessed to measure the levels of proinflammatory and anti-inflammatory cytokines, proliferation rate and FoxP3+Treg cell frequency. Immunohistochemical examinations were performed on spinal cord and brain tissue. RESULTS: Astaxanthin reduced splenocytes proliferation index and proinflammatory cytokine levels, and vice versa increased the anti-inflammatory cytokine levels. Immunohistochemical studies of the spinal cord and brain showed that the infiltration with inflammatory cells was highly confined in the central nervous system. Protective effects of astaxanthin were visible by assigning low score recording in clinical behavior and disease severity. CONCLUSION: Astaxanthin is a powerful tool for intervention in EAE on a model of multiple sclerosis, so it can be studied further to prevent and treat MS (Tab. 2, Fig. 3, Ref. 41).

The effect of resistance training on quadriceps muscle volume and some growth factors in elderly and young men.

Aging process is associated with loss of muscle mass, strength and growth factors dysfunction. Resistance training is one of the effective methods to overcome a decline in muscle mass, strength and also can modulate the level of myostatin, follistatin and insulin-like growth factor-1 (IGF-1) factors. The purpose of this study was to investigate the effect of 8 week resistance training on different anabolic factors which influence muscle hypertrophy in elderly and young men. Fifteen elderly and sixteen young men volunteered and participated in a periodized 3-day per week progressive resistance training program for a total of 8 weeks. Daily calorie intake, muscle volume, cross-sectional area (by computed tomography) and myostatin, follistatin, IGF-1, growth hormone (GH) and testosterone were calculated before and after the training protocol. At the end of the training period, the strength in the elderly group increased significantly compared to the young group (p<0,05); no differences of daily nutrient intake were found in both groups (p>0,05). Quadriceps muscle volume and cross-sectional area increased more in the younger group (p<0,05). Myostatin concentration significantly decreased in both groups (p<0,05), yet the amount of change was not different in either groups (p>0,05). Follistatin and testosterone increased in both groups (p<0,05), but growth hormone and IGF-1 increased in the younger group only (p<0,05). Resistance training improved hypertrophy and lead to anabolic conditions in elder and young subjects, but in different ways. In this regard, GH-IGF-1 axis and growth factors profile at the baseline had an important role in different age-related hypertrophy.

Silver nano particles ameliorate learning and spatial memory of male Wistar rats by prevention of amyloid fibril-induced neurotoxicity.

Alzheimer's disease (AD) is a chronic degenerative disease characterized by the presence of amyloid plaques and neurofibrillary tangles (NFTs), which results into memory and learning impairments. In the present study, we showed that the aggregates formed by a protein that has no link with Alzheimer's disease, namely the hen egg white lysozyme (HEWL), were cytotoxic and decreased spatial learning and memory in rats. The effect of Ag-nano particles (Ag-NPs) was investigated on disruption of amyloid aggregation and preservation of cognitive behavior of rats. Twenty-four male Wistar rats were divided into 4 groups including a control group, and injected with either scopolamine, lysozyme or aggregates pre-incubated with Ag-NPs. Rats' behavior was monitored using Morris water maze (MWM) twenty days after injections. HEWL aggregation in the presence and absence of the Ag-NPs was assayed by Thioflavin T binding, atomic force microscopy and cell-based cytotoxicity assay. Ag-NPs were capable to directly disrupt HEWL oligomerization and the resulting aggregates were non-toxic. We also showed that rats of the Ag-NPs group found MWM test platform in less time and with less distance traveled, in comparison with lysozyme group. Ag-NPs also increased the percentage of time elapsed and the distance swum in the target quadrant in the rat model of AD, in probe test. These observations suggest that Ag-NPs improved spatial learning and memory by inhibiting amyloid fibril-induced neurotoxicity. Furthermore, we suggest using model proteins as a valid tool to investigate the pathogenesis of Alzheimer's disease.

The use of rituximab to prevent severe delayed haemolytic transfusion reaction in immunized patients with sickle cell disease.

BACKGROUND: Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD). STUDY DESIGN: We report an observational study of eight alloimmunized SCD patients with history of severe DHTR who were treated with rituximab before a new transfusion to prevent further immunization and DHTR. RESULTS: Five patients showed a good clinical outcome following transfusion preceded by preemptive treatment with rituximab. The remaining patients presented mild DHTR. In all patients, the results of post-transfusion screening tests were identical to those of pretransfusion tests; no newly formed antibodies were detected. CONCLUSION: These cases suggest that rituximab prevents at least occurrence of newly formed antibodies in high responders and minimizes the risk of severe DHTR. This study confirms that DHTR is complex in SCD and does not rely only on the classical antigens/antibodies conflict. Considering potentially serious adverse effect of rituximab, this treatment should be considered cautiously, and only when transfusion is absolutely necessary in patients with history of severe DHTR linked to immunization.

Loss of normal anagen hair in pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a known cause of loss of 'normal' anagen hair; that is, shedding of intact anagen hairs covered by root sheaths. However, studies on this subject are limited. AIM: To investigate anagen hair shedding in patients with PV, and ascertain its association with disease severity. METHODS: In total, 96 consecutive patients with PV (new patients or patients in relapse) who were admitted to the dermatology wards of a tertiary hospital were enrolled in this study. Demographic data, PV phenotype, disease severity and presence of scalp lesions were recorded. A group of 10-20 hairs were pulled gently from different areas of the scalp (lesional and nonlesional skin) in all patients, and anagen hairs were counted. Disease severity was graded according to Harman score. RESULTS: Anagen hair was obtained by pull test in 59 of the 96 patients (61.5%), of whom 2 had normal scalp. The mean ± SD anagen hair count was 5.9 ± 7.6 (range 0-31). In univariate analysis, anagen hair loss (P < 0.01) and the presence of scalp lesions (P = 0.01) were associated with severe disease. Mean anagen hair count was significantly higher in the severe (mean 6.83 ± 7.89) than the moderate (mean 1.06 ± 1.94) subgroup (P < 0.001). Multivariate analysis confirmed anagen hair loss (OR = 1.16, 95% CI = 1.05-1.28, P < 0.01), but not scalp lesions (P = 0.69) as an independent predictor of disease severity. CONCLUSIONS: According to our study, normal anagen effluvium is a frequent finding in patients with PV, and interestingly, this was observed in nonlesional as well as lesional scalp. In addition, severe anagen hair loss was an independent predictor of the disease severity.

Les anémies aiguës et la stratégie transfusionnelle chez les drépanocytaires adultes: Acute anemias transfusion strategy in adult sickle cell patients.

Worsening of anemia is very common in sickle cell disease. It is important to investigate specific complications related to sickle cell disease but also other causes of anemia in general. Transfusions or exchange transfusions are major therapeutic options and are frequently used for acute complications of sickle cell disease but also for primary and secondary prevention of some of the chronic complications. The transfusion strategy has been modified since the awareness of post-transfusion hemolysis by taking into account the transfusion risk score. A strong collaboration between the patient's expert center, the Blood center and the patient's hospitalization unit is required to make decisions. © 2023 Société nationale française de médecine interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids.

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Evaluation of a prophylactic transfusion program on obstetric outcomes in pregnant women with sickle cell disease: A single centre retrospective cohort study.

OBJECTIVE: To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD). METHODS: This retrospective cohort study included all singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication [year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score] were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death. RESULTS: In total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 [119/148 (80.4%) vs 38/76 (50%); p < 0.001]. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-1.02]. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08-0.97; p = 0.04). CONCLUSION: A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.

Probenecid, an old ß-lactams pharmacokinetic enhancer for a renewed use: A retrospective study.

BACKGROUND: Optimized antibiotic plasma predictor efficacy is essential in systemic infections. The uricosuric agent probenecid inhibits tubular excretion of antibiotics and may be used as ß-lactam pharmacokinetic enhancer (BLPKE), even though few data are currently available for this purpose. METHODS: We conducted a monocentric and retrospective observational study including all patients who received probenecid in combination with parenteral ß-lactam antibiotics for systemic infections from Jan 1, 2014 to Dec 31, 2019. Demographics, infection characteristics, treatment and ATC (antibiotics trough concentration) were investigated. RESULTS: All in all, 38 patients were included. Eight patients had a history of sickle cell disease. Hyperfiltration (defined as eGFR>130mL/min/1.73m2) was detected in twenty-one patients including six with sickle cell disease. Probenecid (500mg q6h orally) was added to antibiotics for a median (IQR) of 13 days (6.75-21.75), after a median (IQR) time lapse of 7 days (4-16) following the initiation of antibiotics. Probenecid was administered for low antibiotic trough concentration in 29 patients, for increased renal clearance in 5 patients and for persisting fever despite antibiotic therapy in 4 patients (including 1 infective relapse). A second plasma trough concentration, following probenecid administration, was available in 19 patients within a median (IQR) 3 days (2-5). Probenecid induced increased ATC in 18/19 patients (94.7%), with a median (IQR) change of +228.4% (IQR 38.7-633). No major adverse effects were reported. CONCLUSION: Probenecid could be a BLPKE. Our data suggest this drug should be used more often to optimize ß-lactam pharmacokinetics in clinical practice.

Tuberculosis in sickle cell disease patients.

OBJECTIVE: Tuberculosis (TB) disease has rarely been reported in patients with sickle cell disease, but it is associated with an increased risk of bacterial infections. In France, sickle cell disease is frequent in populations with the highest prevalence of TB disease. We aimed to highlight clinical aspects of TB disease in patients with sickle cell disease. PATIENTS AND METHODS: Over a 10-year period, we retrospectively included all adults with sickle cell disease who had a positive culture for Mycobacterium tuberculosis managed in the adult sickle cell center of Henri-Mondor hospital. Sickle cell patients with TB disease were matched for comparison to adults without hemoglobinopathy and with documented TB disease in a 1:2 ratio. Logistic regression mixed models were performed. RESULTS: Twelve patients with sickle cell disease and documented TB disease (median age: 29years; IQR [25-34]) were compared to 24 non-sickle cell patients (median age: 33years; IQR [27.5-38.5]). Baseline characteristics were similar between groups except for sickle cell disease. Ten of the 12 patients with sickle cell disease had pulmonary TB. TB disease characteristics were similar between sickle cell and non-sickle cell patients although sickle cell patients had fewer positive sputum smears for acid-fast bacilli (P=0.003) and fewer lung cavitations (P=0.03). CONCLUSIONS: TB disease in sickle cell patients was globally similar to non-sickle cell patients, even though less infectious. Regular follow-up in specialized centers might allow for earlier TB disease diagnosis in sickle cell patients.

Simultaneous Effects of High Intensity Interval Training and Human Amniotic Membrane Scaffold on Rat Tibialis Anterior Vascularization and Innervation after Volumetric Muscle Loss Injury.

BACKGROUND: Despite the high regenerative capacity of skeletal muscle, volumetric muscle loss (VML) is an irrecoverable injury. One therapeutic approach is the implantation of engineered biologic scaffolds. OBJECTIVE: To investigate the simultaneous effect of high intensity interval training (HIIT) and the use of decellularized human amniotic membrane (dHAM) scaffolds on vascularization, growth factor, and neurotrophic factor gene expression, and muscle force generation in the tibialis anterior (TA) of rats after VML injury. METHODS: VML injury was created in the TA of 24 rats, which were randomly divided into two groups-12 animals with and 12 without the use of a dHAM scaffold. After injury, each group was further divided into two groups of 6 animals each-sedentary and HIIT. Blood vessels were visualized and counted by hematoxylin and eosin staining. The PowerLab converter assay was used to evaluate isometric contraction force. The relative expression of neurotrophic factors and growth factor genes was measured with reverse transcription PCR (RT-PCR). RESULTS: The number of blood vessels in the whole regenerating areas showed a significant difference in the dHAM-HIIT and dHAM-sedentary groups compared to the sedentary group without dHAM (p=0.001 and p=0.003, respectively). BDNF and GDNF mRNA levels in the dHAM-HIIT group were significantly (p<0.05) higher than those in other groups; NGF mRNA levels did not differ significantly among groups. Isometric contraction force in the dHAM-HIIT group was significantly (p=0.001) greater compared to the sedentary group without dHAM. CONCLUSION: Combined use of dHAM scaffoldsand HIIT would improve the structure of the injured muscle during regeneration after VML by better vascular perfusion. HIIT leads to greater force generation and innervation by modulating neurotrophic factor synthesis in regenerating muscles.

Betanin effect on PPAR-α and SREBP-1c expression in NMRI mice model of steatohepatitis with fibrosis.

PURPOSE: Betanin is a betacyanin with antioxidant and anti-inflammatory activities whose effects were investigated in a nonalcoholic steatohepatitis (NASH) model. MAIN METHODS: Ninety-six male naval medical research institute (NMRI) mice were divided into eight groups (n = 12) including normal control, high fat diet (HFD), Sham, and positive control treated with trans-chalcone. Three experimental groups were treated with 5 mg/kg, 10 mg/kg or 20 mg/kg betanin, and a betanin protective group was also defined. RESULTS: Four weeks of HFD treatment resulted in steatohepatitis with associated fibrosis. Significant increase was observed in serum levels of triglycerides (TG), total cholesterol (TC), glucose, insulin, leptin, liver enzymes, malondialdehyde (MDA), furthermore insulin resistance and (sterol regulatory element-binding protein-1c) SREBP-1c were detected. Levels of high-density lipoprotein cholesterol (HDL-C), adiponectin, superoxide dismutase (SOD), catalase (CAT), and PPAR-α (peroxisome proliferator-activated receptor-α) considerably decreased. Treatment by betanin, particularly the 20 mg/kg dosage, attenuated these changes. CONCLUSION: Betanin is a potential treating agent of steatohepatitis and works through up-regulation of PPAR-α, down-regulation of SREBP-1c, modification of adipokine levels and modulation of lipid profile.

Molecular testing for respiratory pathogens in sickle cell disease adult patients presenting with febrile acute chest syndrome.

BACKGROUND: Differentiating acute chest syndrome (ACS) from community-acquired pneumonia (CAP) is challenging in adults presenting with major sickle cell disease (SCD) (semiological similarity, rare microbiological documentation). We aimed to assess the usefulness of nucleic acid amplification test (NAAT) for respiratory pathogens, in combination with standard bacteriological investigations, in febrile ACS adult patients presenting with major SCD. METHODS: We performed a prospective, monocentric, observational study of 61 SCD adults presenting with febrile ACS from February 2015 to April 2016. Systematic blood, urine, and respiratory specimens were collected, before antibiotic initiation, for culture, urinary antigen tests, serology, and NAAT for respiratory pathogens. RESULTS: A pathogen was detected in 12 febrile ACS (19.7%): four viruses (6.6%) (Rhinovirus; Influenza A/B), seven bacteria (11.4%) (S. aureus, S. pneumoniae, K. pneumoniae, L. pneumophila, M. pneumoniae), one mixed infection (1.6%) (S. aureus and Influenza B). NAAT only detected L. pneumophila in one case (serogroup 2). Apart from a significantly shorter antibiotic therapy duration (6.1 vs. 7.8 days, P=0.045), no difference was observed between undocumented and microbiologically-documented febrile ACS. CONCLUSION: Using NAAT for the detection of respiratory pathogens in adults presenting with SCD slightly improved the microbiological diagnostic of febrile ACS, although respiratory infections are not the main etiological factor.

[Guidelines for management of adult sickle cell disease]. / Recommandations pratiques de prise en charge de la drépanocytose de l'adulte.

Sickle cell disease is a systemic disease that can potentially involve all organs. As the prevalence of patients with sickle cell disease increases gradually in France, every physician can be potentially involved in the care of these patients. Complications of sickle cell disease can be acute or chronic. Pain is the main symptom and should be treated quickly and aggressively. Acute chest syndrome is the leading cause of acute death and must be prevented, detected, and treated without delay. Chronic complications are one of the main concerns in adults and should be identified as early as possible in order to prevent sequels. Many organs can be involved, including the bones, kidneys, eyes, lungs... The indications for a specific treatment (blood transfusion or hydroxyurea) should be discussed. Health care should be carefully organized to allow both a regular follow-up near the living place and access to specialized departments. We present in this article the French guidelines for the sickle cell disease management in adulthood.

[Study of 206 transfused sickle cell disease patients: immunization, transfusion safety and red blood cell supply]. / Etude d'une cohorte de 206 patients drépanocytaires adultes transfusés: immunisation, risque transfusionnel et ressources en concentrés globulaires.

BACKGROUND: Prevention of hemolytic transfusion reactions depends upon our capacity to prevent allo-immunization and conflicts between antigens of transfused red blood cells and antibodies produced by the recipient. In this study, we show that to secure transfusion of sickle cell disease patients, it is necessary to take into account their immunohematologic characteristics in the organization of transfusion. METHODS AND RESULTS: Immunohematological data of 206 chronically transfused patients have been collected as well as phenotypes of transfused units. In order to prevent allo-immunization against C and E antigens for patients typed D+C-E-c+e+ (56%), 26% of the transfused units were D-C-E-c+e+. We found that 47% of the patients had a history of allo-immunization, whereas only 15% produced an antibody the day of inclusion in the study. The non-detectable antibodies were frequently known as dangerous for transfusion. Finally, this study shows the frequency of anti-D in D+ patients and anti-C in C+ patients, pointing out the question of partial antigens. CONCLUSION: To insure optimal transfusion safety for sickle cell disease patients, three points have to be improved: blood donation within the Afro-Caribbean community living in France, access to history of immuno-hematological data, detection of variant antigens, especially within the RH blood system.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention, diagnosis, treatment.

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.