Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Expression of Non-T Cell Activation Linker (NTAL) in Jurkat Cells Negatively Regulates TCR Signaling: Potential Role in Rheumatoid Arthritis.

T lymphocytes are key players in adaptive immune responses through the recognition of peptide antigens through the T Cell Receptor (TCR). After TCR engagement, a signaling cascade is activated, leading to T cell activation, proliferation, and differentiation into effector cells. Delicate control of activation signals coupled to the TCR is needed to avoid uncontrolled immune responses involving T cells. It has been previously shown that mice deficient in the expression of the adaptor NTAL (Non-T cell activation linker), a molecule structurally and evolutionarily related to the transmembrane adaptor LAT (Linker for the Activation of T cells), develop an autoimmune syndrome characterized by the presence of autoantibodies and enlarged spleens. In the present work we intended to deepen investigation into the negative regulatory functions of the NTAL adaptor in T cells and its potential relationship with autoimmune disorders. For this purpose, in this work we used Jurkat cells as a T cell model, and we lentivirally transfected them to express the NTAL adaptor in order to analyze the effect on intracellular signals associated with the TCR. In addition, we analyzed the expression of NTAL in primary CD4+ T cells from healthy donors and Rheumatoid Arthritis (RA) patients. Our results showed that NTAL expression in Jurkat cells decreased calcium fluxes and PLC-γ1 activation upon stimulation through the TCR complex. Moreover, we showed that NTAL was also expressed in activated human CD4+ T cells, and that the increase of its expression was reduced in CD4+ T cells from RA patients. Our results, together with previous reports, suggest a relevant role for the NTAL adaptor as a negative regulator of early intracellular TCR signaling, with a potential implication in RA.

Adherence to a Mediterranean diet, dyslipidemia and inflammation in familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP). METHODS AND RESULTS: In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p < 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p < 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies. CONCLUSIONS: Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH.

Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19: A Randomized Clinical Trial.

IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.

Adults with familial hypercholesterolaemia have healthier dietary and lifestyle habits compared with their non-affected relatives: the SAFEHEART study.

OBJECTIVE: Healthy lifestyle habits are the cornerstone in the management of familial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affected populations are scarce. The present study analyses dietary habits, adherence to a Mediterranean diet pattern and physical activity in an adult population with FH and compares them with their non-affected relatives. DESIGN: Cross-sectional study. SETTING: Data came from SAFEHEART, a nationwide study in Spain.ParticipantsIndividuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ. RESULTS: Total energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005). CONCLUSIONS: Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group's consumption of saturated fats and sugars still exceeds guidelines.

Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study).

OBJECTIVE: Heterozygous familial hypercholesterolemia (FH) is the most common premature atherosclerotic cardiovascular disease (ASCVD)-related monogenic disorder, and it is associated with ischemic heart disease. There is limited information whether FH increases the risk of peripheral arterial and cerebrovascular disease. Our aim was to analyze ASCVD prevalence and characteristics in different arterial territories in a large FH population, to compare them with an unaffected control population and to determine which factors are associated to ASCVD. APPROACH AND RESULTS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is an ongoing registry of molecularly defined patients with heterozygous FH in Spain. ASCVD in the different arterial territories was analyzed, as well as individual characteristics, genetic variables, and lipid-lowering therapies. The study recruited 4132 subjects (3745 ≥18 years); 2,752 of those enrolled were molecularly diagnosed FH cases. Median age was 44.0 years (45.9% men) and 40 years (46.6% men) in FH patients and unaffected relatives (P<0.001). ASCVD was present in 358 (13.0%) and 47 (4.7%) FH patients and unaffected relatives, respectively (P<0.001). History of premature ASCVD was more prevalent in FH patients (9.4% and 2.4% in FH patients and unaffected relatives, respectively; P<0.001). Coronary artery-related manifestations and peripheral artery disease were more prevalent in FH patients than in controls, but no significant differences were found for cerebrovascular events. Age, body mass index, type 2 diabetes mellitus, high blood pressure, previous use of tobacco, and lipoprotein(a) >50 mg/dL were independently associated with ASCVD. CONCLUSIONS: The prevalence of ASCVD is higher, and the involvement of the arterial territories is different in FH patients when compared with their unaffected relatives. Age, male sex, increased body mass index, hypertension, type 2 diabetes mellitus, smoking habit, and lipoprotein(a) >50 mg/dL were independently associated to ASCVD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02693548.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, <100mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥ 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.

[Familial combined hyperlipidemia: consensus document]. / Hiperlipidemia familiar combinada: documento de consenso.

Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL-cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners.

Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.

SEA 2024 Standards for Global Control of Vascular Risk. / Estándares de la Sociedad Española de Arteriosclerosis 2024 para el control global del riesgo vascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

Effects of Different Heating Treatments on the Antioxidant Activity and Phenolic Compounds of Ecuadorian Red Dacca Banana.

The banana is a tropical fruit characterized by its composition of healthy and nutritional compounds. This fruit is part of traditional Ecuadorian gastronomy, being consumed in a wide variety of ways. In this context, unripe Red Dacca banana samples and those submitted to different traditional Ecuadorian heating treatments (boiling, roasting, and baking) were evaluated to profile their phenolic content by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and the antioxidant activity by ORAC, ABTS, and DPPH assays. A total of sixty-eight phenolic compounds were identified or tentatively identified in raw banana and treated samples, highlighting the content in flavonoids (flavan-3-ols with 88.33% and flavonols with 3.24%) followed by the hydroxybenzoic acid family (5.44%) in raw banana samples. The total phenolic compound content significantly decreased for all the elaborations evaluated, specifically from 442.12 mg/100 g DW in fresh bananas to 338.60 mg/100 g DW in boiled (23.41%), 243.63 mg/100 g DW in roasted (44.90%), and 109.85 mg/100 g DW in baked samples (75.15%). Flavan-3-ols and flavonols were the phenolic groups most affected by the heating treatments, while flavanones and hydroxybenzoic acids showed higher stability against the heating treatments, especially the boiled and roasted samples. In general, the decrease in phenolic compounds corresponded with a decline in antioxidant activity, evaluated by different methods, especially in baked samples. The results obtained from PCA studies confirmed that the impact of heating on the composition of some phenolic compounds was different depending on the technique used. In general, the heating processes applied to the banana samples induced phytochemical modifications. Even so, they remain an important source of bioactive compounds for consumers.

Giant benign lymphangioendothelioma.

Benign lymphangioendothelioma is a rare locally infiltrative vascular neoplasm, presenting as a slow-growing, asymptomatic, reddish-violaceous plaque. Histopathologically, it is characterized by irregular and thin-walled vascular spaces, lined by a single and discontinuous layer of flat endothelial cells, dissecting dermal collagen bundles. We present the case of a 75-year-old man with a giant benign lymphangioendothelioma, to our knowledge, the largest example described in the literature. The immunohistochemical expression of Wilms tumor 1 gene is useful in vascular lesions to differentiate malformations from proliferative endothelial lesions. In our case, the positivity for WT1 supports the neoplastic nature of this lesion.

Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART).

AIM: Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (LLT) in FH patients recruited in SAFEHEART. METHODS AND RESULTS: A cross-sectional analysis of cases recruited in the Spanish FH cohort at inclusion was performed. Demographic, lifestyle, medical and therapeutic data were collected by specific surveys. Blood samples for lipid profile and DNA were obtained. Genetic test for FH was performed through DNA-microarray. Data from 1852 subjects (47.5% males) over 19 years old were analyzed: 1262 (68.1%, mean age 45.6 years) had genetic diagnosis of FH and 590 (31.9%, mean age 41.3 years) were non-FH. Cardiovascular disease was present in 14% of FH and in 3.2% of non-FH subjects (P < 0.001), and was significantly higher in patients carrying a null mutation compared with those carrying a defective mutation (14.87% vs. 10.6%, respectively, P < 0.05). Prevalence of current smokers was 28.4% in FH subjects. Most FH cases were receiving LLT (84%). Although 51.5% were receiving treatment expected to reduce LDL-c levels at least 50%, only 13.6% were on maximum statin dose combined with ezetimibe. Mean LDL-c level in treated FH cases was 186.5 mg/dl (SD: 65.6) and only 3.4% of patients reached and LDL-c under 100 mg/dl. The best predictor for LDL-c goal attainment was the use of combined therapy with statin and ezetimibe. CONCLUSION: Although most of this high risk population is receiving LLT, prevalence of cardiovascular disease and LDL-c levels are still high and far from the optimum LDL-c therapeutic goal. However, LDL-c levels could be reduced by using more intensive LLT such as combined therapy with maximum statin dose and ezetimibe.

The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia.

OBJECTIVES: This study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH). BACKGROUND: Common cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death. RESULTS: We included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%. CONCLUSIONS: CAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.

Proper information during the surgical decision-making process lowers the anxiety of patients with high-grade gliomas.

PURPOSE: We aim to analyse the relationship between the quality of information during the decision-making process regarding surgery to treat high-grade gliomas and the level of anxiety of the patients. METHODS: This is a transversal, descriptive and correlational study on 26 patients with a clinical and radiological diagnosis of high-grade glioma. They scored the quality (in terms of comprehension and satisfaction) of information received about the treatment options and prognosis during the surgical decision-making process, and the Hospital Anxiety and Depression Scale questionnaire (HADS) was applied immediately afterward. RESULTS: Lower levels of anxiety were observed in patients who showed a desire to receive information regarding their illness, those with a higher degree of comprehension, and those with a higher level of satisfaction with the information provided. CONCLUSIONS: An improvement in the communication process contributes to a decrease in the levels of anxiety, and consequently to enhancement of the well-being of these patients.

Hypertrophic Cardiomyopathy and the Brockenbrough-Braunwald-Morrow Phenomenon: A Case Report.

The Brockenbrough-Braunwald-Morrow phenomenon provides objective evidence of the existence and degree of left ventricular outflow tract (LVOT) obstruction, which can be improved with pharmacological therapy, surgical myectomy, or interventional alcohol septal ablation (ASA). This article incorporates contemporary research findings that are useful for the diagnosis and management of this entity. We present the case of a 67-year-old lady with a past medical history significant for hypertension, hyperlipidemia, and coronary artery disease. The patient presented with a complaint of functional class-3 dyspnea on exertion with associated substernal chest tightness radiating to her back that had been worsening for two days prior to admission. An echocardiogram showed left ventricular hypertrophy with septal predominance measuring 17.5 mm in end-diastole and a left ventricular ejection fraction greater than 65%. The LVOT peak gradient was elevated and a positive Brockenbrough-Braunwald-Morrow phenomenon was observed for which a septal myectomy and coronary bypass of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery were performed. The patient had an uneventful postoperative course and her symptoms improved significantly. The Brockenbrough-Braunwald-Morrow phenomenon is useful to determine the degree of LVOT and to confirm the resolution of obstruction after treatment.

In vivo architectural analysis of 3.2 mm clear corneal incisions for phacoemulsification using optical coherence tomography.

PURPOSE: To analyze in vivo the architecture of clear corneal incisions (CCIs) for phacoemulsification using optical coherence tomography (OCT). SETTING: Anterior Segment Department, Asociacion Para Evitar la Ceguera en Mexico, Hospital Dr Luis Sanchez Bulnes, Mexico. METHODS: A prospective masked study analyzed 20 unsutured CCIs placed superiorly and created in a uniplanar fashion with a 3.2 mm slit-angled metal keratome. All wounds were evaluated with a retinal OCT model 1, 3, and 30 days postoperatively. Intraocular pressure (IOP) and incision leakage were checked. The architecture was described according to the angle of incidence, apposition of the epithelial and endothelial margins, and wound sealing. RESULTS: No leakage was detected. The angle varied from 33 to 85 degrees; angles greater than 75 degrees were done by a surgeon in training. Wound apposition at the epithelial margin was achieved in all cases. In contrast, imperfect apposition of the endothelial margin was seen in 45% of incisions on day 1 and in 15% on day 30. Incomplete sealing of the wound was seen by OCT in 25% of cases at 24 hours and persisted in 10% of all cases at 1 month. This gaping occurred on the endothelial side and never translated to the epithelial margin. No statistical correlation was found between gaping and the angle of the incision, IOP variations, or surgeon experience. CONCLUSIONS: Although in vivo CCIs caused minor anatomic imperfections, they were clinically stable independent of incision angle, IOP variation, and surgeon experience. Incision stability may be related to careful wound construction, epithelial viability, stromal edema, and efficient endothelial pumping.

Regional lymphomatoid papulosis of the breast restricted to an area of prior radiotherapy.

We report the case of a 59-year-old woman with type A regional lymphomatoid papulosis (LyP) that was localized to the left breast, a cutaneous area that had received radiotherapy for treatment of a carcinoma of the breast 5 years prior. This report is a rare example of regional LyP with all lesions located in an area of prior radiotherapy.

Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals.

Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins. We have previously found that the adaptor linker for activation of T cells, evolutionarily related to non-T cell activation linker, is cleaved upon proapoptotic stimuli in T lymphocytes and thymocytes, in a tyrosine phosphorylation-dependent fashion. Here, we describe non-T cell activation linker proteolytic cleavage triggered in human B cells and monocytes by Fas cross-linking and staurosporine treatment. Non-T cell activation linker is cleaved, producing an N-terminal fragment of ∼22 kDa, and such cleavage is abrogated in the presence of caspase 8/granzyme B and caspase 3 inhibitors. Moreover, we have identified an aspartic acid residue at which non-T cell activation linker is cleaved, which similar to linker for activation of T cells, this aspartic acid residue is located close to tyrosine and serine residues, suggesting an interdependence of phosphorylation and proteolytic cleavage. Consistently, induction of non-T cell activation linker phosphorylation by pervanadate inhibits its cleavage. Interestingly, the truncated isoform of non-T cell activation linker, generated after cleavage, has a decreased signaling ability when compared with the full-length molecule. Altogether, our results suggest that cleavage of transmembrane adaptors constitutes a general mechanism for signal termination of immune receptors.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: Consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are <130mg/dL for children and young adults, <100mg/dL for adults, and <70mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.