👤 María Mercedes Martín Ordiales

Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by the presence of 2 pathogenic variants in the LDLR, APOB, PCSK9, or LDLRAP1 genes, which cause very high levels of LDL-cholesterol and premature atherosclerotic cardiovascular disease (ASCVD). To analyze the current situation regarding diagnosis, cardiovascular disease, lipid-lowering treatment, and degree of control of lipids in patients with HoFH in the National Dyslipidemia Registry of the Spanish Atherosclerosis Society. Subjects with HoFH, confirmed by the presence of 2 pathogenic variants in the genes mentioned above, included in the registry from 2013 to June 2023 with an updated review were analyzed. Of 71 included subjects with HoFH, 40.8% were women, aged 52 [24-62] years, 57 adults and 13 children. The median follow-up was 7 [4-13] years. Age of diagnosis was 14 [2-26] years, with 10% of ASCVD at diagnosis and 27% of current ASCVD at 40.6 (13.4) years of age; 38% were on PCSK9 inhibitors, 9 patients on lomitapide, 9 on LDL apheresis, and 1 patient on evinacumab. Subjects with more than 4 therapies achieved >80% reduction in LDLc. In the last visit, the median LDLc was 139.3 [89.4-204.2] mg/dL. ASCVD was strongly associated with male sex and family history of ASCVD, relative risk 5.26 (1.53-18.10) and 2.53 (1.03-6.26), P < .05, respectively. Only 18% and 10% meet the recommended LDLc goal in primary and secondary prevention respectively. The current situation of HoFH in Spain is better than expected, with marked reductions in LDLc levels with new treatments. In this population, recommended LDLc goals are difficult to achieve despite maximum lipid-lowering therapy. ASCVD has been reduced and delayed by 2 decades. Show less

Superficial fungal infections are common in dermatology and are often caused by opportunistic species in the Candida and Malassezia genera. The aim of this study was to analyze changes in the expression of genes coding for enzymes involved in the biosynthesis of glycosaminoglycans (GAGs) chains following the adherence of Candida and Malassezia yeasts to skin cell lines. Gene expression was analyzed using reverse transcriptase-quantitative polymerase chain reaction assays. Interactions between the yeasts and the skin cells induced the following changes in genes involved in the biosynthesis of heparan sulfate and chondroitin sulfate: downregulation of CHPF in keratinocytes and downregulation of EXT1, EXT2, CHSY3, and CHPF in fibroblasts. Adherence to fibroblasts had an even greater effect on GAG biosynthetic enzymes, inducing the downregulation of 13 genes and the upregulation of two (CHST15 and CHST7). Interactions between yeasts and skin cells might affect the binding affinity of GAG chains, possibly changing their ability to function as receptors for pathogens and interfering with a key stage at the start of infection. Show less