Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study.

AIM: We aimed to describe clinical and genetic characteristics, lipid-lowering treatment and atherosclerotic cardiovascular disease (ASCVD) outcomes over a long-term follow-up in homozygous familial hypercholesterolemia (HoFH). METHODS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is a long-term study in molecularly diagnosed FH. Data analyzed in HoFH were prospectively obtained from 2004 until 2022. ASCVD events, lipid profile and lipid-lowering treatment were determined. RESULTS: Thirty-nine HoFH patients were analyzed. The mean age was 42 ± 20 years and nineteen (49%) were women. Median follow-up was 11 years (IQR 6,18). Median age at genetic diagnosis was 24 years (IQR 8,42). At enrolment, 33% had ASCVD and 18% had aortic valve disease. Patients with new ASCVD events and aortic valve disease at follow-up were six (15%), and one (3%), respectively. Median untreated LDL-C levels were 555 mg/dL (IQ 413,800), and median LDL-C levels at last follow-up was 122 mg/dL (IQR 91,172). Most patients (92%) were on high intensity statins and ezetimibe, 28% with PCSK9i, 26% with lomitapide, and 23% with lipoprotein-apheresis. Fourteen patients (36%) attained an LDL-C level below 100 mg/dL, and 10% attained an LDL-C below 70 mg/dL in secondary prevention. Patients with null/null variants were youngers, had higher untreated LDL-C and had the first ASCVD event earlier. Free-event survival is longer in patients with defective variant compared with those patients with at least one null variant (p=0.02). CONCLUSIONS: HoFH is a severe life threating disease with a high genetic and phenotypic variability. The improvement in lipid-lowering treatment and LDL-C levels have contributed to reduce ASCVD events.

Dental Transmigration: An Observational Retrospective Study OF52 Mandibular Canines.

The aim of this study was to analyze the prevalence of transmigrated canines in a Spanish population by evaluating their clinical and radiological characteristics. The descriptive observational study obtained 6840 orthopantomographs from all patients seeking dental care in the years 2017-21 via the Patient Reception Service and Dentistry Service at the Faculty of Dentistry at the Complutense University of Madrid and the Central Hospital of the Red Cross of Madrid (Spain). In total, 52 patients presented transmigrated canines, establishing a prevalence of 0.76%. This sample comprised 28 women and 24 men. Whenever a transmigrated canine was identified, a CBCT scan was obtained and used to evaluate the clinical and radiological variables associated with canine transmigration. The predominant side of the transmigration was the left (57.69%) compared to the right side (42.30%). The position of the canine, in order of frequency, according to the Mupparapu classification, corresponded to type IV (42.30%), type II (36.53%), type I (15.38%), and type V (5.76%), with no type III transmigrations found. Clinical manifestations were only recorded in 17.30% of cases, and 11.53% of the radiological findings showed the presence of tooth cysts that were confirmed by histopathological studies. Other impactions, in addition to the transmigrated canine, were found in five patients (9.61%), with the majority being the presence of third molars.

Analysis of the Radiological Changes of the Sinus Membrane Using Cone Beam Computed Tomography and Its Relationship with Dental Treatments. A Retrospective Study.

The aim of this study was to identify the most relevant dental factors and iatrogenic causes in the development of pathological changes to the sinus membrane and to analyse their possible influence on the development of odontogenic sinusitis. A descriptive, observational study was designed, with 276 patients who had been evaluated via cone beam computed tomography, analysing possible sinus thickening factors, such as apical infections, endodontic treatments, periodontitis, radicular cysts and impacted teeth, as well as iatrogenic factors caused by implant treatments or the development of oroantral communications produced during tooth extraction manoeuvres. Among the dental factors, periodontitis (47.1%), apical pathology (23.5%) and endodontic treatments (23.1%) were the predominant causes of sinus membrane thickening that most frequently produced an occupancy between 2 and 10 mm. Regarding the implant treatments, the placement of implants through the floor of the maxillary sinus was the main cause (9.8%), followed by sinus elevation techniques (6.2%). Dental extraction was the first cause of oroantral communication (5.0%), being the procedure that caused the greatest thickening of the sinus membrane. This study highlights the importance of dental treatments and iatrogenic factors in sinus pathology, and the need for diagnostic interrelations between the different specialists who address this pathology.

Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: Insights from SAFEHEART registry.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.

Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up.

BACKGROUND: Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment targets; large registries that reflect real-life clinical practice can uniquely provide this information. OBJECTIVES: We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry. METHODS: The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT). RESULTS: The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals. CONCLUSIONS: Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.

Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR.

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), an autosomal dominant inherited disorder associated with an increased risk of premature atherosclerosis. The aim of this study was to characterize the LDLR mutations in a group of 476 apparently non-related Spanish FH patients. The promoter region and the 18 exons with their flanking intron sequences of the LDLR gene were screened by PCR-SSCP analysis and DNA sequencing. In addition, we tested for the presence of the mutation p.R3500Q in the gene coding for apolipoprotein B-100 (apo B-100). We found 77 mutations previously described, and 39 novel mutations affecting the LDLR gene: 8 missense, 5 nonsense, 15 frameshift, 5 splicing, 4 in frame, one nucleotide change in the non-coding sequence of exon 1, and one silent variant. We have identified al least one of these LDLR gene mutations in 329 subjects (69%). Four patients were homozygous, 4 patients were compound heterozygous, 48 patients were found to carry two different sequence variants in the same allele and 4 patients carried three different sequence variants in the same allele. Additionally, 4 subjects were carriers of the p.R3500Q mutation in the apo B gene. All of these findings indicate that there is a broad spectrum of mutations and sequence variants in the LDLR gene causing FH in Spain.

Retinopatía diabética / Diabetic retinopathy

La retinopatía diabética es la complicación más frecuente y conocida de la diabetes mellitus de larga duracion. Se revisan los conceptos actuales sobre incidencia, diagnóstico, pronóstico, periodo de seguimiento, factores de riesgo y tratamiento en los estadios de edema macular clínicamente significativo y retinopatía proliferativa.

Tenectomía parcial posterior del oblicuo superior de Prieto*Díaz / Parcial tenectomy of Prieto-Diaz

Se presentan tres casos de anisotropías en A en los que se logran buenos resultados quirúrgicos siguiendo la técnica de tenectomía parcial posterior descrita por Prieto*Díaz para corregir moderados grados de anisotropías en A que no excedan 25 D.P. de incomitancia