Gardos channelopathy is a rare dehydrated hereditary stomatocytosis caused by gain-of-function KCNN4 mutations. We report a pediatric case due to a recurrent p.Ser314Pro variant, representing the first description outside the Italian population. Over a comprehensive 6-year clinical follow-up, the patient exhibited a stable baseline course punctuated by infection-triggered hemolytic crises, exacerbated by concomitant bronchial asthma. Prospective data demonstrated persistent iron redistribution without systemic overload under conservative management. This case expands the geographic spectrum of the p.Ser314Pro variant, highlights clinical lessons for conservative monitoring, and emphasizes the utility of early next-generation sequencing integration.

Coagulation factor VII (FVII) is a vitamin K-dependent glycoprotein and serves as a key initiator of the extrinsic coagulation pathway. Hereditary FVII deficiency is an autosomal recessive genetic disorder with a highly heterogeneous bleeding phenotype. It is the most prevalent among rare hereditary bleeding disorders. Among the various genotypes, complex heterozygous variants are of particular importance in hereditary coagulation factor deficiency. This study reports a case of a patient with hereditary FVII deficiency. The patient presented for planned surgery for renal cysts. Preoperative evaluation revealed abnormal coagulation indicators; therefore, the surgery was temporarily postponed. Further investigations to clarify the cause revealed markedly prolonged prothrombin time (PT), significantly reduced FVII activity (FVII:C), and mildly decreased FVII antigen (FVII:Ag). Complex heterozygous variants (p.Ile303Thr and p.Cys389Gly) were identified, confirming the diagnosis of hereditary FVII deficiency. Thrombin generation assay (TGA) and thromboelastography (TEG) suggested that the patient's global coagulation capacity was not substantially impaired. No specific treatment was administered, and regular follow-up was conducted. In this compound heterozygous patient with markedly reduced FVII:C without bleeding, TGA and TEG may offer a better assessment of bleeding risk than FVII:C alone, and family screening facilitates identification and management of at-risk individuals.

This study investigated the protective effect and mechanism of propofol (PPF) against hydrogen peroxide (H2O2)-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). An H2O2-induced injury model was established and treated with various concentrations of PPF. The results demonstrated that PPF significantly alleviated H2O2-induced cytotoxicity, apoptosis, proliferative suppression, and cellular senescence while enhancing cell migration and tube formation. Mechanistically, PPF increased the activities of antioxidant enzymes (SOD, CAT, GSH-Px), reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, suppressed the release of inflammatory cytokines (IL-6, IL-8, TNF-α), promoted endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production, and maintained intracellular adenosine triphosphate (ATP) content. Under conditions of chronic, sustained oxidative stress, PPF remained effective in activating the NRF2/HO-1 pathway and alleviating cellular damage. Furthermore, PPF facilitated nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and up-regulated the expression of its downstream target heme oxygenase-1 (HO-1). Inhibition of NRF2 using ML385 significantly attenuated the antioxidant, anti-senescent, and cytoprotective effects of PPF. In conclusion, PPF mitigates H2O2-induced endothelial cell injury and functional impairment by activating the NRF2/HO-1 pathway and modulating the ROS-eNOS/NO-ATP axis, suggesting its potential as an endothelial protective agent in clinical settings.

Sickle cell disease (SCD) is a genetic disorder strongly shaped by social, racial, and territorial inequalities. We identified, mapped, and characterized the population living with SCD in a state in Northeast Brazil and examined how fragmented institutional records affect the epidemiological visibility of the disease. We carried out a cross-sectional, multi-source study using institutional datasets on people with SCD. Records from these sources were consolidated and complemented by active tracing to update information. Adults were interviewed to describe their sociodemographic conditions, clinical profile, access to care, and experiences within the health system. Official counts substantially underestimated the affected population, reflecting unlinked information systems and limited record updating. The number of identified individuals increased from 266 to 471, corresponding to an estimated prevalence of 1.14 cases per 10,000 inhabitants. Interviewed adults (n = 119) showed high social vulnerability, with a predominance of Black participants, low educational attainment, low levels of income, and reliance on social benefits. A considerable proportion of participants were diagnosed only in adulthood. Specialized care was concentrated in the state capital and one additional urban center, creating major geographic barriers for residents of interior municipalities. Pain was frequent, severe, and functionally limiting, and many participants reported pain disbelief and stigmatizing labels during care. The gap between official records and identified cases indicates a significant weakness in health surveillance. Social vulnerability, geographically concentrated services, and routine delegitimization of pain suggest that historical inequalities, including racism, remain embedded even within a universal public health system such as Brazil's.

Voxelotor, a hemoglobin S polymerization inhibitor, has been shown to reduce anemia in sickle cell anemia (SCA) but its effects on vaso-occlusive crisis frequency are limited. Its recent market withdrawal due to concerns over treatment-related excess mortality highlights the need for a better understanding of its mechanisms of action, especially with similar compounds under development. We investigated, in vitro, the effects of voxelotor on red blood cells (RBCs) from SCA patients, in hypoxia and normoxia. Parameters included: 1) RBC senescence markers including phosphatidylserine (PS) and CD47 exposure, calcium and reactive oxygen species (ROS) content measured with flow cytometry; 2) RBC aggregation assessed by light transmission; 3) RBC deformability using ektacytometry under shear stress, osmotic, and oxygen gradients. Voxelotor decreased RBC PS exposure in both hypoxia and normoxia but increased ROS levels. Voxelotor increased RBC aggregation and RBC deformability, decreased Ohyper (indicating decreased cell hydration state). The extent of RBC deformability increase with voxelotor was negatively correlated with fetal hemoglobin levels. While voxelotor demonstrated beneficial effects on RBC deformability and sickling propensity, its impact on RBC aggregation properties and ROS generation requires further investigation to better understand its different mechanisms of action.

Blood viscosity is recognized as a key determinant in the pathophysiology of vaso-occlusive crises (VOC) in sickle cell anemia (SCA). However, its longitudinal relationship with changes in VOC frequency over time remains poorly understood. The present study analyzed the associations between the changes in blood rheological parameters and the changes (delta) in the rate of VOC over time in 63 SCA patients. VOC rates (calculated over the 3 years preceding each blood sampling) and biological parameters were measured at two separate occasions, spaced by at least 3 yrs. (mean difference between the two measurements: 5.7 ± 2.0 years). A positive correlation was observed between the delta-VOC rate and the percentages of change in white blood cells, lactate dehydrogenase and blood viscosity. A multivariate linear regression was performed to test the independent association between the delta-VOC rate and the percentages of change in these biological parameters. The model was statistically significant (R[2] = 0.47, p < 0.01), and blood viscosity was the only parameter independently associated with the percentage of change in VOC rate (β coefficient = 0.025, 95% CI: 0.009-0.040, p < 0.01). Our study demonstrated that steady-state blood viscosity is a valuable biomarker in SCA, given its associations with temporal variations of VOC frequency.

Circadian rhythms regulate immune cell activity, but their impact on hematopoietic stem cell infusion remains unclear. This retrospective study evaluated 177 severe aplastic anemia (SAA) patients undergoing unrelated donor hematopoietic stem cell transplantation (URD-HSCT) (2012-2023) to assess impacts of circadian infusion timing. No significant differences emerged between early and late infusion groups in cumulative incidence (CUI) of neutrophil/platelet engraftment, acute/chronic graft-versus-host disease (aGVHD/cGVHD), or CMV/EBV viremia. Notably, CUI of grade III-IV aGVHD was higher in the early group (5.7%, 95% CI: 1.8%-13.4%) versus 0% in the late group (95% CI: 0%-3.4%, P = 0.03). Five-year overall survival (OS: 87% vs. 93%, P = 0.1871), failure-free survival (FFS: 85% vs. 92%, P = 0.1389), and graft-versus-host disease/relapse-free survival (GRFS: 76% vs. 82%, P = 0.2781) showed no statistical disparities. Subgroup analysis revealed older patients (>30 years) receiving late peripheral blood HSCT had superior OS (78% vs. 97%, P = 0.0154) and FFS (78% vs. 94%, P = 0.0390). These data suggest that the timing of infusion may affect the risk of GVHD and the survival of older patients, for whom delayed infusion may confer a survival benefit.