"SCULP" study: The benefits of skin graft pellets on the pain of sickle cell leg ulcers (SCLU).

BACKGROUND: Leg ulcers associated with major sickle cell disease (SCLU) are a chronic, painful complication, often treated by autologous skin graft. The analgesic effect of skin grafting in SCLU is poorly studied. The aim of this study was to evaluate the effect of skin grafting on the pain and healing of SCLU. METHODS: Patients hospitalized for SCLU skin grafting were included in a retrospective and prospective observational cohort, between 2019 and 2023: 53 autologous pinch grafts were performed on a total of 35 SCLUs in 25 sickle cell patients. The primary endpoint was the evaluation of the analgesic effect of the skin graft, measured by visual analog scale (VAS) and weekly cumulative analgesic consumption between day (D)0, D7 and D30. Wound healing was assessed by variation in wound areas between D0 and D30. RESULTS: Twenty-five patients with a median age range of 45.5years old were included, 68% were men, SS genotype was present in 96% of the cases. At D7, a significant decrease in VAS and consumption of analgesics of all classes was observed. At D30, only a significant decrease in VAS and consumption of mild opioids was present, as well as a significant reduction in wound surface area compared with D0. CONCLUSION: Pinch grafts have a significant early analgesic effect in the management of patients with SCLU, and significantly notice reduction of wound surface area within one month.

Preventive treatment of unruptured intracranial aneurysms in adult patients with sickle cell anemia: A cohort study.

BACKGROUND AND PURPOSE: Intracranial aneurysms are frequent in patients with sickle cell anemia, while subarachnoid hemorrhage is a major cause of death and disability in young adult patients. Several characteristics, such as younger age and smaller size at rupture, may incline therapeutic decision towards exclusion treatments. Clinical guidelines on treatment of unruptured intracranial aneurysms in this population are still missing. We aimed to assess the safety and efficacy of the treatment of unruptured intracranial aneurysm in patients with sickle cell anemia, using an adapted hematological preparation regimen. PATIENTS AND METHODS: Adult patients with sickle cell anemia and treated unruptured aneurysms by endovascular therapy or neurosurgery were included in this retrospective cohort study. Treatment decision was reached after multi-disciplinary assessment. A pre-operative blood transfusion protocol was undertaken targeting a HbS below 30%. Demographic data, hematological preparation parameters and clinical and radiological outcomes were documented. RESULTS AND CONCLUSIONS: Twenty-five procedures were performed in 18 patients encompassing 19 aneurysms treated by embolization and 6 by surgery. Median age at treatment was 34 years-old and median aneurysm dome size was 4.4 mm. Immediate aneurysm exclusion rate was 85.7% after endovascular therapy and 100% after neurosurgery. Median follow-up was 6 months, with all patients being asymptomatic at last follow-up. Two transitory ischemic neurological deficits, as well as four cases of iodine-induced encephalopathy were identified after embolization. No complication occurred after surgery. Endovascular therapy by coiling and neurosurgical treatment of unruptured intracranial aneurysms appears to be safe in patients with sickle cell anemia and should be considered given the specific hemorrhagic risk observed in this population. A rigorous hematological preparation, associated with a dedicated peri­operative protocol and an adequate therapeutic strategy are essential prerequisites.

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.

Factors predictive of leg-ulcer healing in sickle cell disease: a multicentre, prospective cohort study.

BACKGROUND: Leg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing and recurrence of LUs is lacking. OBJECTIVES: To determine clinical and biological factors associated with SCD-LU complete healing and recurrence. METHODS: This prospective, observational cohort study was conducted at two adult SCD referral-centre sites (2009-2015) and included 98 consecutive patients with at least one LU lasting ≥ 2 weeks. The primary end points compared patients with healed vs. nonhealed LUs at week 24, and patients with vs. without recurrence during follow-up. RESULTS: The median (interquartile range) LU area, duration and follow-up were, respectively, 6·2 cm2 (3-12·8), 9 weeks (4-26) and 65·8 weeks (23·8-122·1). At week 24, LUs were healed in 47% of patients, while 49% of LUs recurred. Univariate analyses identified inclusion LU area < 8 cm2 (82% vs. 35%; P < 0·001), inclusion LU duration < 9 weeks (65% vs. 35%; P = 0·0013) and high median fetal haemoglobin level (P = 0·008) as being significantly associated with complete healing at week 24, and low lactate dehydrogenase level (P = 0·038) as being associated with recurrence. Multivariate analyses retained LU area < 8 cm2 (odds ratio 6·73, 95% confidence interval 2·35-19. 31; P < 0·001) and < 9 weeks' duration (OR 3·19, 95% confidence interval 1·16-8·76; P = 0·024) as being independently associated with healing at week 24. Factors independently associated with recurrence could not be identified. CONCLUSIONS: SCD-LU complete healing is independently associated with the clinical characteristics of LUs rather than the clinical or biological characteristics of SCD.

New insights into the natural history of hepatitis E virus infection through a longitudinal study of multitransfused immunocompetent patients in France.

Little is known about the natural history of Hepatitis E virus (HEV) infection in immunocompetent individuals. The prevalence, the course of infection and the occurrence of transmission by transfusion were investigated in multitransfused immunocompetent patients/blood donor pairs included in a longitudinal sample repository collection and followed up between 1988 and 2010. Ninety-eight subjects aged 6-89 years and suffering from acquired haemoglobinopathies were tested for HEV markers (IgM, IgG and RNA) in serial samples collected every 2 or 3 years. Eighteen patients (18.4%) were positive for HEV-IgG at baseline with a prevalence increasing from 12.5% below 26 years to 32% above 56 years. Nine patients remained IgG positive along the study and nine lost their antibodies after a mean follow-up of 7.4 years (1-22 years). One seropositive patient showed an increase of IgG level and RNA-HEV reappearance 1 year after inclusion, suggesting a reinfection and one seroconversion, probably acquired through blood transfusion was observed. This first longitudinal study including immunocompetent individuals confirms that HEV infection is common in Western Europe and that transfusion transmission occurs probably less frequently than expected. In addition, seroreversion and reinfection seem to be common. This suggests that the anti-HEV may not persist overtime naturally. However, repeat exposure to the virus related to the high prevalence of HEV infection may result in a sustainable specific IgG response.

[Issues and difficulties in the relationship between patients and caregivers in painful sickle cell vaso-occlusive crisis]. / Enjeux et difficultés de la relation entre soignants et patients drépanocytaires au cours de la crise douloureuse aiguë.

Sickle cell patients in acute pain situation experiment cognitive, behavioral and emotional changes that can accentuate their pain and disrupt communication with caregivers. On the other hand, caregivers have to face pain assessment difficulties and their own psychological reactions to their patient's pain. The gap between the patient's experience and caregiver's evaluation can lead to conflict and non-adherence treatment, and have a direct impact on the sickle cell disease prognosis. There is nothing inevitable about these phenomena, whose knowledge allows the action and opens up prospects for improving the management of sickle cell disease pain. This article is a narrative review updating the interactions between acute pain and some configurations, such as the inability to discern emotions, catastrophizing, post-traumatic stress or feeling ostracized. The overestimation of patient's addiction by caregivers also influences the pain itself. Open communication, as well as some treatments, medicated or not, a consistent institutional organization and a multidisciplinary approach altogether have an analgesic role by acting on pain cognitive and emotional components.

Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a randomized controlled study.

PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06-0.68; p = 0.009]. CONCLUSIONS: iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION: NCT00748423.

[French guidelines for the management of adult sickle cell disease: 2015 update]. / Recommandations françaises de prise en charge de la drépanocytose de l'adulte: actualisation 2015.

Sickle cell disease is a systemic genetic disorder, causing many functional and tissular modifications. 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 and chronic. Pain is the main symptom and should be treated quickly and aggressively. In order to reduce the fatality rate associated with acute chest syndrome, it must be detected and treated early. Chronic complications are one of the main concerns in adults and should be identified as early as possible in order to prevent end organ damage. Many organs can be involved, including bones, kidneys, eyes, lungs, etc. The indications for a specific treatment (blood transfusion or hydroxyurea) should be regularly discussed. Coordinated health care should be carefully organized to allow 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.

The risk of going abroad in sickle cell disease: a study of 148 adults.

Going abroad is considered to be a risk for acute complications in patients with sickle cell disease (SCD). Our objective was to describe the risk in our cohort of adult SCD patients. Complications occurring during a trip were recorded from adults with SCD seen at a routine visit in a referral centre and during hospitalizations for acute complications. One hundred and eight patients participated; mean age=26.8 (± SD 7.3; range 18-56) years. Eighty-two patients travelled in the previous year, half of them in Africa. Among patients going to endemic areas, 68% of patients received chemoprophylaxis against malaria. Health problems occurred in 53 (65%) travellers: vaso-occlusive crisis (VOC) (68%), fever (19%), diarrhoea (19%), broncho-pulmonary symptoms (11%), headaches (8%), vomiting (6%), and cutaneous wound (4%). Sixteen patients required hospitalization; no specific infection was diagnosed. The prevalence of VOC during the trip was higher than the frequency of VOC during the year before. Patients who developed severe complications were not the most symptomatic patients from SCD. Our study showed that going abroad is associated with a large number of acute complications in adults with SCD. Complications were mostly VOC, and severity was unpredictable. Prevention should be improved.

Is procalcitonin a marker of invasive bacterial infection in acute sickle-cell vaso-occlusive crisis?

Fever is often present during painful vaso-occlusive crisis (VOC) in sickle-cell disease (SCD), but does not always indicate infection. The aim of our study was to test procalcitonin as a marker of invasive bacterial infection in VOC. Consecutive SCD adults hospitalized for VOC were included. Data were collected at admission and within 24 h after the onset of fever. We distinguished patients with clinically defined and microbiologically documented invasive bacterial infection from patients with no evidence of invasive bacterial infection and who fared well without antibiotics. One hundred and twelve patients were enrolled (61% females, median age 23 years, 88% homozygous SCD). All patients with procalcitonin (PCT) level ≥1 µg/L had an invasive bacterial infection, but two patients (33%) with an invasive bacterial infection had a PCT level <1 µg/L. High levels of PCT indicate invasive bacterial infection. However, a single low PCT level without follow-up measurement cannot rule out an invasive bacterial infection and should not withhold the prescription of antibiotics.

[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.

Sickle cell leg ulcers: a frequently disabling complication and a marker of severity.

BACKGROUND: Leg ulcers are a poorly known and underestimated complication of sickle cell disease (SCD), but in our experience they often appear as a severely disabling condition, associated with the most severe forms of the disease. OBJECTIVES: To assess the characteristics, complications, repercussion on quality of life and associations of SCD ulcers. METHODS: Case series of 20 patients followed in a French referral centre for SCD and who had previous/present leg ulcers. RESULTS: Median ulcerated area was 12 cm2 and median time spent with ulcers was 29.5 months. Locoregional infections developed in 85%, ankle stiffness in 50% and mood disorders in 85%. Ninety per cent of patients needed analgesics, 20% being opioids. Median loss of time from work was 12.5 months. The Short Form 36 Health Survey showed physical and mental component summary scores of 41.5 and 40.7, respectively, indicating severe alteration close to that found in lung cancer or haemodialysis. Two categories of SCD leg ulcers were distinguished, defined by a 1-year duration cut off. The 'prolonged' ulcers had larger surfaces, tended to recur more frequently and led to more infection and depression. Several SCD complications were associated with leg ulcers, notably priapism, pulmonary hypertension, stroke and acute chest syndrome. CONCLUSIONS: Leg ulcers are a major complication of SCD, given their severe consequences and frequent association with other specific organ damage, and they constitute in their 'prolonged' form a severely disabling condition that remains an important therapeutic challenge.

Unusual sites of Salmonella osteoarthritis in patients with sickle cell disease: two cases.

Salmonella osteoarticular infections involve mainly long bones such as the femur, tibia, and humerus in patients with sickle cell disease (SCD). We report here two unusual cases of Salmonella osteoarthritis affecting sacroiliac and sternoclavicular joints in two patients with SCD, one patient also being followed for rheumatoid arthritis. Because of misleading presentation, diagnosis of septic osteoarthritis in patients with SCD requires a high index of suspicion and an early treatment.

Acute myocardial ischemia after high-dose therapy with BEAM regimen.

We describe a case of acute myocardial ischemia following carmustine treatment during the BEAM regimen. Despite this, full completion of the autologous peripheral stem-cell transplant was possible.