Sublingual Microcirculation Specificity of Sickle Cell Patients: Morphology of the Microvascular Bed, Blood Rheology, and Local Hemodynamics.

Patients with sickle cell disease (SCD) have poorly deformable red blood cells (RBC) that may impede blood flow into microcirculation. Very few studies have been able to directly visualize microcirculation in humans with SCD. Sublingual video microscopy was performed in eight healthy (HbAA genotype) and four sickle cell individuals (HbSS genotype). Their hematocrit, blood viscosity, red blood cell deformability, and aggregation were individually determined through blood sample collections. Their microcirculation morphology (vessel density and diameter) and microcirculation hemodynamics (local velocity, local viscosity, and local red blood cell deformability) were investigated. The De Backer score was higher (15.9 mm-1) in HbSS individuals compared to HbAA individuals (11.1 mm-1). RBC deformability, derived from their local hemodynamic condition, was lower in HbSS individuals compared to HbAA individuals for vessels < 20 µm. Despite the presence of more rigid RBCs in HbSS individuals, their lower hematocrit caused their viscosity to be lower in microcirculation compared to that of HbAA individuals. The shear stress for all the vessel diameters was not different between HbSS and HbAA individuals. The local velocity and shear rates tended to be higher in HbSS individuals than in HbAA individuals, notably so in the smallest vessels, which could limit RBC entrapment into microcirculation. Our study offered a novel approach to studying the pathophysiological mechanisms of SCD with new biological/physiological markers that could be useful for characterizing the disease activity.

Impact of a submaximal mono-articular exercise on the skeletal muscle function of patients with sickle cell disease.

PURPOSE: Sickle cell disease (SCD) patients exhibit a limited exercise tolerance commonly attributed to anaemia, as well as hemorheological and cardio-respiratory abnormalities, but the functional status of skeletal muscle at exercise is unknown. Moreover, the effect of SCD genotype on exercise tolerance and skeletal muscle function has been poorly investigated. The aim of this study was to investigate skeletal muscle function and fatigue during a submaximal exercise in SCD patients. METHODS: Nineteen healthy individuals (AA), 28 patients with sickle cell anaemia (SS) and 18 with sickle cell-haemoglobin C disease (SC) performed repeated knee extensions exercise (FAT). Maximal isometric torque (Tmax) was measured before and after the FAT to quantify muscle fatigability. Electromyographic activity and oxygenation by near-infrared spectroscopy of the Vastus Lateralis were recorded. RESULTS: FAT caused a reduction in Tmax in SS (- 17.0 ± 12.1%, p < 0.001) and SC (- 21.5 ± 14.5%, p < 0.05) but not in AA (+ 0.58 ± 29.9%). Root-mean-squared value of EMG signal (RMS) decreased only in SS after FAT, while the median power frequency (MPF) was unchanged in all groups. Oxygenation kinetics were determined in SS and AA and were not different. CONCLUSION: These results show skeletal muscle dysfunction during exercise in SCD patients, and suggest different fatigue aetiology between SS and SC. The changes in EMG signal and oxygenation kinetics during exercise suggest that the greater skeletal muscle fatigue occurring in SCD patients would be rather due to intramuscular alterations modifications than decreased tissue oxygenation. Moreover, SS patients exhibit greater muscle fatigability than SC.

Feasibility of a screening and prevention procedure for risks associated with dysphagia in older patients in geriatric units: the DYSPHAGING pilot study protocol.

BACKGROUND: Dysphagia, particularly sarcopenic dysphagia, is frequent in frail older patients. Sarcopenic dysphagia is a swallowing disorder caused by sarcopenia, corresponding to a loss of muscle mass and strength. It frequently leads to inhalation and to the decrease of food intake, leading the patient to enter a vicious circle of chronic malnutrition and frailty. The awareness of the major health impacts of sarcopenic dysphagia is recent, explaining a low rate of screening in the population at risk. In this context, methods of prevention, evaluation and intervention of sarcopenic dysphagia adapted to the most at-risk population are necessary. METHODS: The DYSPHAGING (dysphagia & aging) pilot study is a prospective, multicentre, non-comparative study aiming to estimate the feasibility of an intervention on allied health professionals using the DYSPHAGING educational sheet designed to implement a two-step procedure 'screen-prevent' to mitigate swallowing disorders related to sarcopenic dysphagia. After obtaining oral consent, patients are screened using Eating Assessment Tool-10 Score. In case of a score≥2, procedures including positional manoeuvres during mealtimes, food and texture adaptation should be implemented. The primary endpoint of the study is the feasibility of this two-step procedure (screening-prevention measures) in the first 3 days after patient's consent.The study will include 102 patients, with an expected 10% rate of non-analysable patients. Participants will be recruited from acute geriatric wards, rehabilitation centres and long-term care units, with the hypothesis to reach a feasibility rate of 50% and reject a rate lower than 35%. ETHICS AND DISSEMINATION: The study protocol was approved according to French legislation (CPP Ile-de-France VII) on 15 February 2023. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05734586.

Is Skeletal Muscle Dysfunction a Limiting Factor of Exercise Functional Capacity in Patients with Sickle Cell Disease?

Patients with sickle cell disease (SCD) have reduced functional capacity due to anemia and cardio-respiratory abnormalities. Recent studies also suggest the presence of muscle dysfunction. However, the interaction between exercise capacity and muscle function is currently unknown in SCD. The aim of this study was to explore how muscle dysfunction may explain the reduced functional capacity. Nineteen African healthy subjects (AA), and 24 sickle cell anemia (SS) and 18 sickle cell hemoglobin C (SC) patients were recruited. Maximal isometric torque (Tmax) was measured before and after a self-paced 6-min walk test (6-MWT). Electromyographic activity of the Vastus Lateralis was recorded. The 6-MWT distance was reduced in SS (p < 0.05) and SC (p < 0.01) patients compared to AA subjects. However, Tmax and root mean square value were not modified by the 6-MWT, showing no skeletal muscle fatigue in all groups. In a multiple linear regression model, genotype, step frequency and hematocrit were independent predictors of the 6-MWT distance in SCD patients. Our results suggest that the 6-MWT performance might be primarily explained by anemia and the self-paced step frequency in SCD patients attempting to limit metabolic cost and fatigue, which could explain the absence of muscle fatigue.

Sickle Cell Disease and Infections in High- and Low-Income Countries.

Infections, especially pneumococcal septicemia, meningitis, and Salmonella osteomyelitis, are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). SCD increased susceptibility to infection, while infection leads to SCD-specific pathophysiological changes. The risk of infectious complications is highest in children with a palpable spleen before six months of age. Functional splenectomy, the results of repeated splenic infarctions, appears to be a severe host-defense defect. Infection is the leading cause of death, particularly in less developed countries. Defective host-defense mechanisms enhance the risk of pneumococcal complications. Susceptibility to Salmonella infections can be explained at least in part by a similar mechanism. In high-income countries, the efficacy of the pneumococcal vaccine has been demonstrated in this disease. A decreased in infection incidence has been noted in SCD patients treated prophylactically with daily oral penicillin. Studies in low-income countries suggest the involvement of a different spectrum of etiological agents.