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Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

HMG-CoA reductase inhibitors or statins are effective in both the primary and secondary prevention of coronary heart disease, the extent of benefit being proportional to the reduction in low density lipoprotein (LDL) cholesterol achieved. Atorvastatin, a newly licensed compound, reportedly lowers LDL with greater efficacy than other statins. The mechanism of this action was, therefore, explored in twenty patients with refractory familial hypercholesterolemia who received in a single-blind sequence simvastatin 40 mg/day, placebo and atorvastatin 10 mg/day each for 4 weeks. At the end of the placebo period the effects of single 40-mg doses of simvastatin and atorvastatin on plasma levels and urinary excretion of mevalonic acid, indices of HMG-CoA reductase activity, were compared. Administration of atorvastatin 10 mg daily for 1 month lowered LDL cholesterol by 32.5%, compared with placebo (P = 0.0001), which was 4.5% less than the decrease after simvastatin 40 mg daily (P = 0.33). The area under the plasma curve and urinary mevalonic acid/ creatinine ratio were both significantly less during the 24 h after a single dose of atorvastatin 40 mg than after a single dose of simvastatin 40 mg (P < 0.01). These findings suggest that the greater efficacy of atorvastatin compared with simvastatin is due to more prolonged inhibition of HMG-CoA reductase, presumably reflecting longer residence of atorvastatin or its active metabolites in the liver.

Aim: The use of sealants is an effective measure for the prevention of pit and fissure caries in children and it has been well documented by several studies In order to plan and establish a preventive national programme, it is important to know the epidemiological pattern in an Italian paediatric population, correlated to the risk of caries, DMFT and other sociodemographic factors., Methods: This study was conducted on 2,442 children aged between 6 and 12 years attending the paediatric dentistry department of the University of L'Aquila, Italy. In addition to the oral examination, a questionnaire was administered on bad habits and the family perception of sealing. For descriptive analysis, the sample was stratified into two groups based on the presence/absence of at least one tooth with sealant. The differences between discrete and nominal variables, reported as absolute and percentage frequencies, were assessed by applying the χ2 test or the Fisher's exact test, as appropriate. Continuous variables were expressed in terms of mean values and their standard deviation(±DS) and the differences between the two groups under consideration were analysed through Student's t-test. The tests used are two-way and a significance level of 5% was applied. The statistical analysis was carried out using the statistical package STATA/IC 15.0 (StataCorp LLC, Texas, USA)., Conclusion: The application of sealants to healthy occlusal surfaces is the best aid in preventing the development of caries in these areas, and this is especially important in childhood and adolescence, when the incidence of this pathology is particularly high.

Cellular and humoral immune responses to tetanus-diphtheria vaccine (Td) were assessed in human leukocyte antigen (HLA)-typed Italian military personnel who received multiple concomitant vaccines. Td-specific antibodies and T-lymphocytes were measured in individuals with one (group-1) and more than one (group-2) Td boosters. A third group (group-3), who received several vaccines, but not Td, was studied to verify the hypothesis of the polyclonal B-cell activation as mechanism for antibody persistence. The antibody response to Td toxoids was higher in group-1, who showed lower baseline antibody levels, than in group-2 subjects. The antibody response to tetanus was higher than to diphtheria toxoid in both groups. No correlation between antibody and cellular response, and no interference in the response to Td by co-administration of different vaccines were observed. HLA-DRB1∗01 allele was detected at significant higher frequency in subjects unable to double the baseline anti-diphtheria antibody levels after the vaccination. Anti-tetanus and diphtheria antibodies half-lives were assessed and the long-lasting persistence above the threshold for protection (0.1 IU/ml) was estimated in over 65 and 20 years, respectively. No significant increase of anti-diphtheria antibodies was observed in consequence of polyclonal B-cell activation. This study emphasizes the duration of Td vaccination-induced seroprotection, suggesting that re-vaccination should probably be performed at intervals longer than 10 years. No reciprocal interference by concomitantly administered vaccines has been observed. HLA-DRB1∗01 allele was significantly associated with anti-diphtheria defective response. Finally, this study does not confirm that anti-diphtheria antibody levels are maintained by polyclonal B-cell activation. Clinical trial registry: The study was registered with NCT01807780., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Immunogenicity of 13-valent pneumococcal polysaccharide (PnPS) conjugate vaccine (PCV13) was evaluated in 38 rheumatoid arthritis patients under immunosuppressive treatment and 20 healthy controls (HC). Antibodies to all PnPS and diphtheria-toxin analogue conjugate protein were measured pre- (T0), 1 (T1), 6 (T2), 12 (T3) months post-immunization. Patients and HC had similar response to individual PnPS. Mean antibody levels to all PnPS but one doubled at T1 compared with T0, with T3 persistence for only 8-7/13 PnPS. Baseline antibody levels was inversely associated with the rate of responders at T1 (T1/T0≥2) to 11/13 PnPS. Few subjects reached protective IgG levels against some serotypes frequently isolated in Italian patients with invasive pneumococcal disease. Antibody response was not influenced by therapy, except the one to PS7F, which was reduced by tumor necrosis factor-α-inhibitors. Vaccination increased also anti-diphtheria IgG. Despite this study substantially confirmed the PCV13 immunogenicity in immunocompromised patients, it also revealed some limitations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The 1st International Standard for Diphtheria Antitoxin Human (coded 10/262) was established by the World Health Organization Expert Committee on Biological Standardization in 2012. This paper describes the production, characterization and calibration of the new standard which is intended for use in the standardization of assays used to measure diphtheria antibody responses in human serum. The new standard was calibrated in terms of the International Standard for Diphtheria Antitoxin Equine in an international collaborative study. A total of 8 participants from 8 different countries performed in vivo and/or in vitro toxin neutralization tests and returned data that was used to assign units to the proposed new standard. The new standard has a diphtheria antitoxin potency of 2 IU/ampoule and is predicted to be stable. A follow up study was performed to assess commutability of the new standard. The follow up study was an existing external quality assessment, modified to include the new standard. Results obtained suggest that the new standard is commutable, showing comparable behaviour to native human serum samples in the majority of the assays compared, and is therefore suitable for use as a reference preparation in assays used to measure the level of anti-diphtheria antibodies in human serum., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Objectives: a) To examine the clinical utility of transcranial Doppler and continuous-wave Doppler in monitoring nonsurgical patients with severe intracranial disease until intracranial circulatory arrest and brain death; and b) to investigate if hemodynamic phenomena that occur under such conditions are correlated to specific transcranial Doppler and continuous-wave Doppler waveforms., Design: Prospective, observational study., Setting: Medical intensive care unit (ICU) in a city hospital., Patients: Thirty-seven consecutive patients with Glasgow Coma Scores of < 7., Measurements and Main Results: Transcranial Doppler examination was conducted transtemporally on the left- and right-middle cerebral artery four times daily. In all patients, transcranial Doppler waveforms exhibited high resistance profiles with low, zero, and then reversed diastolic flow velocity. Only three waveform patterns, consisting of diastolic reverse flow without diastolic forward flow, brief systolic forward flow, and undetectable flow in the middle cerebral artery were registered in the 22 brain-dead patients, but in none of the other comatose patients., Conclusion: Transcranial Doppler offers a noninvasive method to document deterioration of cerebral perfusion pressure and in the future could be included in protocols for brain death diagnosis.