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Acute myocarditis (AM) is a rare but severe disease affecting patients of all age. Large multicentric data comparing children and adults are lacking. We aimed to elucidate differences in presentation, management, and outcomes of AM across age groups. A comprehensive French national cohort study, encompassing 53 pediatric and adult units from March 2020 to November 2021, was analysed. Baseline characteristics and evolution, management and in-hospital complications were collected. Major cardiovascular events (MACE) within 30 days included all-cause death, cardiogenic shock, cardiac arrest, ventricular arrhythmias, or complete AV block. We included 745 AM patients (328 children and 417 adults), mainly male (73.4%) with a median age of 19.8 years [IQR: 12.5–30.9]. Multisystem inflammatory syndrome (MIS) was more prevalent among pediatric cases (69.8%), whereas infectious aetiology dominated in adults (13.4 vs. 52.4%). Children exhibited a more severe clinical presentation, with increased risk of heart failure (15.9 vs. 7.2%) and cardiogenic shock (14.4 vs. 6.9%), requiring higher use of inotropes (25.0 vs. 9.4%), vasopressors (12.0 vs. 6.2%), and ventilatory support (12.5 vs. 7.7%). Cardiac treatments such as beta-blockers (33.4 vs. 84.4%) or ACE/ARB (37.3 vs. 63.1%) were less often used in children whereas corticosteroids (68.3 vs. 14.3%) and immunomodulators (65.1 vs. 4.5%) were more often used. MACE occurrence was substantial but not significantly different between children and adults (18.1 vs. 13.4%). Extra-cardiac manifestations at admission were significant predictors of MACE (aOR: 2.40 [1.43–4.38]), regardless of multisystem inflammatory syndrome (MIS) status. AM exhibits variations in presentation, aetiologies, and management, but shares a comparable 30-day prognosis in children and adults. [ABSTRACT FROM AUTHOR]

Genetic diagnosis of familial hypercholesterolemia (FH) remains unexplained in 30 to 70% of patients after exclusion of monogenic disease. There is now a growing evidence that a polygenic burden significantly modulates LDL-cholesterol (LDL-c) concentrations. Several LDL-c polygenic risk scores (PRS) have been set up. However, the balance between their diagnosis performance and their practical use in routine practice is not clearly established. Consequently, we set up new PRS based on our routine panel for sequencing and compared their diagnostic performance with previously-published PRS. After a meta-analysis, four new PRS including 165 to 1633 SNP were setup using different softwares. They were established using two French control cohorts (MONA LISA n=1082 and FranceGenRef n=856). Then the explained LDL-c variance and the ability of each PRS to discriminate monogenic negative FH patients (M-) versus healthy controls were compared with 4 previously-described PRS in 785 unrelated FH patients. Between all PRS, the 165-SNP PRS developed with PLINK showed the best LDL-c explained variance (adjusted R²=0.19) and the best diagnosis abilities (AUROC=0.77, 95%CI=0.74-0.79): it significantly outperformed all the previously-published PRS (p<1 × 10−4). By using a cut-off at the 75th percentile, 61% of M- patients exhibited a polygenic hypercholesterolemia with the 165-SNP PRS versus 48% with the previously published 12-SNP PRS (p =3.3 × 10−6). These results were replicated using the UK biobank. This new 165-SNP PRS, usable in routine diagnosis, exhibits better diagnosis abilities for a polygenic hypercholesterolemia diagnosis. It would be a valuable tool to optimize referral for whole genome sequencing. [ABSTRACT FROM AUTHOR]

• In the Multiple Sclerosis field, the prescription of subsequent therapies following Alemtuzumab, as mandated by label guidance for a treatment-free period of at least 5 years, presents a complex challenge. • This case-series presents our real-world experience transitioning patients from Alemtuzumab to Siponimod in the context of active Secondary progressive Multiple Sclerosis, elucidating outcomes and considerations that challenge conventional recommendations. • In our cohort, Siponimod was associated with a stable disease course and cognitive evaluation and to a stable lymphocytic count after 12 months on therapy. Alemtuzumab, a humanized anti‐CD52 monoclonal antibody, is approved for treatment of highly active relapsing multiple sclerosis (MS) but requires vigilant post-treatment monitoring due to associated risks. The prescription of subsequent therapies following Alemtuzumab, as mandated by label guidance for a treatment-free period of at least 5 years, presents a complex challenge, particularly if there is concurrent conversion to secondary progressive disease course. We described a case-series of five patients starting therapy with Siponimod and followed up for 12 months period converted to secondary progressive MS previously exposed to Alemtuzumab. All patients received Siponimod 2 mg. Clinical evaluation measured with Expanded Disability Status Scale and cognitive evaluation measured with Brief International Cognitive Assessment for Multiple Sclerosis were stable after 12 months on therapy. No severe lymphopenia was recorded, nor serious adverse events. In conclusion, the long-term management of patients treated with Alemtuzumab transitioning to secondary progressive MS requires a proactive and multidisciplinary approach. By addressing the challenges associated with treatment limitations and short-term monitoring recommendations while considering alternative therapeutic options like Siponimod, clinicians can optimize outcomes and ensure continuity of care for individuals with MS. [ABSTRACT FROM AUTHOR]

• Unrelated patients with suspected familial hypercholesterolemia • Monogenic etiology of familial hypercholesterolemia in 25.6% adults and 77% children • LDL-cholesterol as a major parameter to suspect monogenic hypercholesterolemia Familial hypercholesterolemia (FH) is the most common genetic disorder associated with a high risk for premature atherosclerotic cardiovascular disease attributable to increased levels of LDL-cholesterol (LDL-C) from birth. FH is both underdiagnosed and undertreated. We describe the clinical, biological, and genetic characteristics of 147 patients in France with clinical FH (including a group of 26 subjects aged < 20 years); we explore how best to detect patients with monogenic FH. We retrospectively reviewed all available data on patients undergoing genetic tests for FH from 2009 to 2019. FH diagnoses were based on the Dutch Lipid Clinics Network (DLCN) scores of adults, and elevated LDL-C levels in subjects < 20 years of age. We evaluated LDLR, APOB , and PCSK9 status. The mutations of adults (in 25.6% of all adults) were associated with DLCN scores indicating "possible FH," "probable FH, and "definitive FH" at rates of 4%, 16%, and 53%, respectively. The areas under the ROC curves of the DLCN score and the maximum LDL-C level did not differ (p = 0.32). We found that the pediatric group evidenced more monogenic etiologies (77%, increasing to 91% when an elevated LDL-C level was combined with a family history of hypercholesterolemia and/or premature coronary artery disease). Diagnosis of monogenic FH may be optimized by screening children in terms of their LDL-C levels, associated with reverse-cascade screening of relatives when the children serve as index cases. [ABSTRACT FROM AUTHOR]

• High-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression. • Ocrelizumab and natalizumab could be the best strategy in naive highly active multiple sclerosis patients. • NEDA-3 after three years of treatment may be achieved in a high percentage of patients starting treatment with NAT or OCR. in the early stages of Multiple Sclerosis (MS), initiating high-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression, especially in highly active MS patients (HAMS). Natalizumab (NAT) and Ocrelizumab (OCR) are recognized as HE DMTs with significant anti-inflammatory effects. This study investigates NEDA-3 achievement in treatment-naïve HAMS patients receiving NAT or OCR over three years. we retrospectively enrolled treatment-naïve HAMS patients undergoing NAT or OCR, collecting demographic, clinical, and instrumental data before and after treatment initiation to compare with propensity score analysis disease activity, time to disability worsening, and NEDA-3 achievement. we recruited 281 HAMS patients with a mean age of 32.7 years (SD 10.33), treated with NAT (157) or OCR (124). After three years, the Kaplan-Meier probability of achieving NEDA-3 was 66.0 % (95 % CI: 57.3 % - 76.0 %) with OCR and 68.2 % (95 % CI: 59.9 % - 77.7 %) with NAT without significant differences between the two groups (p = 0.27) starting HE DMT with monoclonal antibodies for HAMS could achieve NEDA-3 in a high percentage of patients without differences between NAT or OCR. [ABSTRACT FROM AUTHOR]

• Odontoplasty in ponies improved the digestibility of fibrous fractions of tifton hay. • Ponies after dental treatment spent more time feeding. • Odontoplasty in ponies with mild dental alterations did not alter nutrient intake. • Odontoplasty in ponies with mild dental alterations did not affect fecal fiber size. We aimed to evaluate the effects of dental correction on voluntary nutrient intake, time of intake, apparent digestibility and fecal particle size in Brazilian ponies. Twelve mares, with no history of previous dental treatments, housed in individual pens and fed a diet based on tifton 85 were used. The study comprised two consecutive experimental phases, pre and post dental treatment. Each phase consisted of 15 days for adaptation to the pen and treatment and 5 days for data collection, totaling 20 days. To calculate nutrient intake and digestibility coefficients, samples of diets, leftovers, and feces were analyzed for dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude fat (CF), mineral matter (MM), organic matter (OM), and non-fiber carbohydrates (NFC). Food intake time was recorded using a digital video recorder. Fecal particles were analyzed by wet sieving. Dental correction did not influence the intake of DM, CP, NDF, CF, and OM by the animals. However, there was an increase in NFC intake from 0.12 kg to 0.14 kg and in food intake time from 654.50 ± 138.98 to 774.95 ± 167.14. There was a decrease in the digestibility of CP from 0.08 kg to 0.04 kg and an increase in the digestibility of NDF from 0.65 kg to 0.82 kg. Although odontoplasty increased the time of hay intake and the digestibility of the fibrous fractions of the feed of ponies, it did not influence the intake of nutrients and the size of the fecal particles. [ABSTRACT FROM AUTHOR]

• κ-index correlates negatively with verbal memory in MS. • Brain MRI-visible lesions do not mediate this link. • B cell activation may worsen cognitive function in MS. Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5–195.2 vs. median 37.2, range 2.3–396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans. [ABSTRACT FROM AUTHOR]

Background and Aims: Behavioral and biological risk factors (BBRF) explain part of the variability in socioeconomic differences in health. The present study aimed at evaluating education differences in incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) in Italy and the role of BBRF.Methods and Results: All subjects aged 30-74 years (n = 132,686) who participated to the National Health Interview Surveys 2000 and 2005 were included and followed-up for ten years. Exposure to smoking, physical activity, overweight/obesity, diabetes and hypertension at baseline was considered. Education level was used as an indicator of socioeconomic status. The outcomes were incident cases of CVD and CHD. Hazard ratios by education level were estimated, adjusting for sociodemographic covariates and stratifying by sex and geographic area. The contribution of BBRF to education inequalities was estimated by counterfactual mediation analysis, in addition to the assessment of the risk attenuation by comparing the models including BBRF or not. 22,214 participants had a CVD event and 6173 a CHD event. After controlling for sociodemographic factors, the least educated men showed a 21% higher risk of CVD and a 17% higher risk of CHD compared to the most educated (41% and 61% among women). The mediating effect (natural indirect effect) of BBRF between extreme education levels was 52% for CVD and 84% for CHD among men (16% among women for CVD).Conclusions: More effective strategies aiming at reducing socioeconomic disparities in CVD and CHD are needed, through programs targeting less educated people in combination with community-wide initiatives. [ABSTRACT FROM AUTHOR]

Background: Although patients with systemic right ventricle (SRV) represent a significant proportion of patients with congenital heart disease (CHD) implanted with cardiac resynchronization therapy (CRT), there are limited and conflicting data in this specific patient group.Objective: We aimed to analyze outcomes of patients with SRV implanted with a CRT device.Methods: Data were analyzed from an observational, retrospective, multicenter cohort study including all patients with CHD implanted with a CRT device from 6 French centers from 2004 to 2020. Response to CRT was defined as an increase in systemic ventricular ejection fraction of ≥10% and/or an improvement in New York Heart Association functional class by at least 1 grade.Results: A total of 85 patients with CHD were enrolled (mean age 39.8 ± 20.0 years; 55 [64.7%] males; 25 defibrillators [29.4%]), including 31 patients with SRV (36.5%) (mean age 43.9 ± 19.8 years; 16 [51.6%] males). The mean change in QRS duration after implantation was similar as compared with patients with systemic left ventricle (-46 ± 26 ms vs -35 ± 32 ms; P = .16). During a mean follow-up of 5.1 ± 3.5 years, late complications included 2 lead dysfunctions (6.5%), 3 CRT-related infections (9.7%), and 1 inappropriate implantable cardioverter-defibrillator shock (3.2%). The proportion of CRT responders at 6, 12, and 24 months were 82.6%, 80.0%, and 77.8% in patients with SRV vs 66.7%, 64.3%, and 69.6% in patients with systemic left ventricle (P = NS).Conclusion: In this multicenter cohort, one-third of patients with CHD implanted with a CRT device had SRV. CRT in patients with SRV was associated with a high rate of responders, comparable to that of patients with systemic left ventricle. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute myocarditis (AM) is a rare but severe disease affecting patients of all age. Large multicentric data in children and comparison with adult are lacking. We aim to compare AM presentation, management, and outcomes according to age of the patients at admission and to identify factors associated with 30-day prognosis. All cases of AM were included between March 2020 and November 2021 in 64 adults and children centres in France. We collected baseline data, AM presentation and evolution, in-hospital management and in-hospital complications. All-cause death and major cardiovascular events (MACE) (acute pulmonary oedema, cardiogenic shock, or cardiac arrest) were investigated with a 30-day systematic follow-up. NCT04375748 In total, 745 AM patients (417 adults and 328 children) were included, mainly men (73.4%) with a median age of 19.8 [12.5–30.9] years old. Children had more extra-cardiac manifestations (78.3% vs. 24.0%, P < 0.01), more clinical signs of heart failure (14.9% vs. 7.0%, P < 0.01) and shock (47.9% vs. 12.7%, P < 0.01). They also had lower left and right ventricular function on TTE. The main aetiology of AM was viral myocarditis (32.6% of the overall population) with a predominance in adults (50 vs. 20% in children). Children had less toxic myocarditis (0 vs. 2.6%, P < 0.01), immunologic myocarditis (1.0 vs. 7.0%, P < 0.01), vaccine-related myocarditis (5.0 vs. 9.0%, P < 0.01) and idiopathic AM (9.0 vs. 28.0%, P < 0.01). Multisystem inflammatory syndrome was predominant in children (66.0 vs. 1.0%, P < 0.01). Cardiac treatments as beta blockers (84.4 vs. 33.4%, P < 0.01) or ACE/ARB2 (63.1 vs. 37.3%, P < 0.01) were significantly more often used in adults. On the contrary, corticosteroids (68.3 vs. 14.3%, P < 0.01) and immunomodulators including antiviral and/or IGIV were significantly more used in children (65.1 vs. 4.5%, P < 0.01). In-hospital complications occurred more in children (23.8 vs. 14.3, P < 0.01) especially acute kidney injury (11.0 vs. 5.3%, P < 0.01) and cardiogenic shock (15.2 vs. 8.1%, P < 0.01). At 30-day, adults presented more composite endpoint including death, cardiac arrest, cardiogenic shock, and acute pulmonary oedema (3.4 vs. 0.9% respectively in adults and children, P < 0.03) AM presentation, aetiologies and management differs according to age. Despite higher rate of in-hospital complications in children, the 30-day prognosis is worse in adult. [ABSTRACT FROM AUTHOR]

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings. [ABSTRACT FROM AUTHOR]

Background and Aims: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients.Methods and Results: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001).Conclusion: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19.Trial Registration: NCT04318366. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) may associate with clinical manifestations, ranging from alterations in smell and taste to severe respiratory distress requiring intensive care, that might associate with weight loss and malnutrition. We aimed to assess the incidence of unintentional weight loss and malnutrition in COVID-19 survivors. In this post-hoc analysis of a prospective observational cohort study, we enrolled all adult (age ≥18 years) patients with a confirmed diagnosis of COVID-19 who had been discharged home from either a medical ward or the Emergency Department of San Raffaele University Hospital, and were re-evaluated after remission at the Outpatient COVID-19 Follow-Up Clinic of the same Institution from April 7, 2020, to May 11, 2020. Demographic, anthropometric, clinical and biochemical parameters upon admission were prospectively collected. At follow-up, anthropometrics, the mini nutritional assessment screening and a visual analogue scale for appetite were assessed. A total of 213 patients were included in the analysis (33% females, median age 59.0 [49.5–67.9] years, 70% overweight/obese upon initial assessment, 73% hospitalised). Sixty-one patients (29% of the total, and 31% of hospitalised patients vs. 21% of patients managed at home, p = 0.14) had lost >5% of initial body weight (median weight loss 6.5 [5.0–9.0] kg, or 8.1 [6.1–10.9]%). Patients who lost weight had greater systemic inflammation (C-reactive protein 62.9 [29.0–129.5] vs.48.7 [16.1–96.3] mg/dL; p = 0.02), impaired renal function (23.7% vs. 8.7% of patients; p = 0.003) and longer disease duration (32 [27–41] vs. 24 [21–30] days; p = 0.047) as compared with those who did not lose weight. At multivariate logistic regression analysis, only disease duration independently predicted weight loss (OR 1.05 [1.01–1.10] p = 0.022). COVID-19 might negatively impact body weight and nutritional status. In COVID-19 patients, nutritional evaluation, counselling and treatment should be implemented at initial assessment, throughout the course of disease, and after clinical remission. NCT04318366. • Weight loss and risk of malnutrition are prevalent, yet likely underestimated collaterals of COVID-19. • Clinically significant weight loss was evident in both patients managed at home and hospitalised. • Weight loss was predicted by disease duration, highlighting the important role of disease severity and inflammation. • All COVID-19 patients should undergo nutritional assessment/interventions, in all settings and during the recovery phase. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cardiac catheterization (CC) has largely improved the diagnosis and treatment of congenital heart disease in children over the last decades, but it leads to exposure to low doses of X-rays. Children have a greater radiation sensitivity, however, little is known about the long-term radiation associated cancer risks. This study aims to assess the risk of lympho-hematopoietic malignancies among children diagnosed and/or treated with CC. The COCCINELLE cohort includes children from 15 French paediatric cardiology departments who underwent a first CC between 2000–2013, before 16 years old. The cohort was linked with national registries to identify cancer cases and collect information on predisposing factors to cancer (PF). Individual cumulative doses to active bone marrow (ABM) were calculated with the PCXMC software, based on detailed dosimetric information retrieved from reports of 1,139 CC procedures. Standardised incidence ratios (SIRs) and relative risks (RR) of haematological malignancies associated with the 2-year lagged ABM dose were calculated. The cohort included 17,104 children, followed 6.5 years on average. 22,227 CC procedures were collected, with a mean individual ABM cumulative dose of 3.0 mGy. 38 lympho-hematopoietic malignancies were counted (23 lymphoma and 15 leukemia). A significant excess of cancer incidence was observed (SIR = 3.8 [95% confidence interval 2.9; 4.9]), which wasn't anymore observed after excluding patients with PF (SIR = 1.3 [0.6; 2.7]). The ABM dose wasn't significantly associated with the risk of lympho-hematopoietic malignancies (RR/mGy = 1.00 [0.88; 1.10]) or lymphoma (RR/mGy = 1.03 [0.90; 1.14]) after adjustment for attained age, gender and PF. No significant increase of cancer incidence was observed after excluding patients with PF and no dose-response relationship was observed between the risk of lympho-hematopoietic malignancies or lymphoma and cumulative ABM dose arising from CC procedure. The extension of the COCCINELLE study and the European Harmonic project will help to better assess health effects of CC exposure during childhood. [ABSTRACT FROM AUTHOR]

Severe hypertriglyceridemia (HTG), characterized by triglycerides (TG) permanently over 10 mmol/L, may correspond to familial chylomicronemia syndrome (FCS), a rare disorder. However, hypertriglyceridemic patients more often present multifactorial chylomicronemia syndrome (MCS), characterized by highly variable TG. A few nonsense variants of LMF1 gene were reported in literature in FCS patients. In this study, we described a woman with an intermittent severe HTG. NGS analysis and the sequencing of a long range PCR product revealed a homozygous deletion of 6507 base pairs in LMF1 gene, c.730-1528_898-3417del, removing exon 6, predicted to create an in-frame deletion of 56 amino acids, p.(Thr244_Gln299del). Despite an exon 6 homozygous deletion of LMF1 , the patient's highly variable lipid phenotype was suggestive of MCS diagnosis. • Deleterious variations in the LMF1 gene leading to hyperchylomicronemia are rare. • No copy number variation was previously reported in the LMF1 gene. • The study describes the first deletion in the LMF1 gene, removing exon 6. • This deletion is associated with a multifactorial chylomicronemia syndrome phenotype. [ABSTRACT FROM AUTHOR]

• CSF NfL at onset predicted subsequent disease activity in early MS. • Early MS patients with future disease activity had higher CSF NfL concentration. • A baseline CSF NfL ≥ 500 pg/mL identified patients with future disease activity. The prediction of disease activity in patients with a first demyelinating event suggestive of multiple sclerosis (MS) is of high clinical relevance. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has shown to have prognostic value in MS patients. In this work, we measured CSF NfL in patients at the first demyelinating event in order to find a cut-off value able to discriminate patients who will have disease activity from those who will remain stable during the follow-up. We included CSF samples collected within 30 days after the onset of the first demyelinating event from 32 patients followed-up for 3.8 ± 2.5 years. CSF NfL was measured with a newly developed in-house enzyme linked immunosorbent assay (ELISA). At the first demyelinating event, patients with subsequent disease activity had significantly higher baseline CSF NfL values compared to clinically and radiologically stable patients (median 812.5 pg/mL, range 205–2359 pg/mL vs 329.5 pg/mL, range 156–3492 pg/mL, p = 0.002). A CSF NfL cut-off value of 500 pg/mL significantly discriminated these two groups of patients with a 90% sensitivity and an 83.3% specificity. Our results confirm that CSF NfL is a prognostic marker in the very early phases of MS. The validation of a cut-off value of 500 pg/mL could provide clinicians with a dichotomous variable that can simplify the prognostic assessment of patients at the first demyelinating event. [ABSTRACT FROM AUTHOR]

In this study, the effect of early exercise, age, body weight (BW), and growth on the articular cartilage and subchondral bones of the tarsocrural joints was evaluated in 40 young Mangalarga Marchador horses allowed free choice exercise in pasture. Twenty of the horses had additional controlled exercise 3 days per week from a mean age of 30 ± 20 days until 36 months. The training program consisted of an increasing number of 15-minute gallop sprints in an oval paddock with a concrete floor covered by a thick layer of sand. BW, withers height (WH), and neck circumference were measured and body condition scores, cresty neck scores, and obesity index were rated. For each tarsus and foal, 5 standard radiographic projections were evaluated. All evaluations were performed at time point 1 (18 months of age) and time point 2 (36 months of age). Radiographic changes suggestive of tarsal osteoarthritis were observed in two male foals of the trained group at time point 2 (10% of 20). No horses from the untrained group developed OA. Training of the foals did not result in alterations of the morphometric parameters evaluated. However, significant differences were found between time point 1 and 2 in trained and untrained animals. At time point 2, the animals presented greater weights and WHs than at time point 1. We conclude that specific levels of physical activity during initial development do not increase the prevalence of osteoarthritic injury in Mangalarga Marchador foals. • Besides the exercise other factors may also be associated with the development of OA. • The training time and body weight are positively related to the development of OA. • Controlled physical activity does not increase the prevalence of OA in MM foals. [ABSTRACT FROM AUTHOR]

Background Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B–containing lipoproteins from both the intestine and the liver. Objective To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported. Results Both patients are compound heterozygotes for p.(Arg540His) and either c.708_709del p.(His236Glnfs*11) or c.1344+3_1344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3_1344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons. Conclusion Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established. Highlights • Genetic, clinical, ultrastructural, and biological characteristics of a new abetalipoproteinemia (ABL) case. • Postprandial studies in the new ABL case and 7 heterozygous carriers. • Normal lipid absorption in MTTP heterozygotes except if additional APOB alteration. • Need for genetic cascade screening in ABL relatives. • Need for liver and lipid absorption monitoring in ABL heterozygotes. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias and sudden death are recognized complications of tetralogy of Fallot (TOF). Electrophysiological study (EPS) is increasingly performed prior to pulmonary valve replacement (PVR) in these patients to evaluate and treat the arrhythmic substrate. We aimed to assess the value of cardiac magnetic resonance (CMR) to refine pre-operative risk stratification in this population. A prospective multicenter study was conducted to systematically assess EPS in patients with TOF referred for PVR from January 2020 to December 2021. Multiple CMR parameters were analyzed and correlated with EPS results. Among a total of 120 patients enrolled, 108 (90.0%) patients who had a CMR prior to EPS were analyzed. A VA was inducible in 24 (22.2%) patients. Clinical characteristics of patients associated with EPS results are presented in Table 1. Concerning CMR variables, mean RV end-diastolic volume index was 157 ± 39 ml and was not statistically different in patients with positive vs. negative EPS (164 ± 49 vs. 155 ± 35, P = 0.395). However, a RV/LV end-diastolic volume index ratio > 2.4 was significantly associated with a higher likelihood of inducibility (OR 3.10, 95%CI 1.14–8.74, P = 0.040). Mean RV end-systolic volume index tended to be upper in patient with positive EPS (101 ± 35 vs. 86 ± 26, P = 0.072). The RV ejection fraction measured on CMR also tended to be slightly lower in patients with positive EPS (40 ± 7 vs. 43 ± 9, P = 0.069) unlike the LV ejection fraction (P = 0.600). Mean pulmonary annulus diameter were also significantly associated with positive EPS (31 ± 8 vs. 26 ± 7 mm, OR 1.10 [1.02–1.18] per 1 mm increment, P = 0.012). A pulmonary annulus diameter > 28 mm was associated with an OR of 2.9 [1.10–8.11] (P = 0.047). In multivariable analysis, RV/LV end-diastolic volume index ratio > 2.4 (OR 4.6 [1.2–22.5], P = 0.036) and history of atrial arrhythmia (OR 10.9 [2.6–60.8], P = 0.002) remained independent predictors of VA inducibility (Figure 1). In patients with TOF prior to PVR, RV/LV end-diastolic volume index ratio and pulmonary annulus diameter are associated with ventricular arrhythmia inducibility during EPS. CMR parameters, in combination with other clinical factors, may be useful to improve pre-operative risk stratification. [ABSTRACT FROM AUTHOR]

• Multiple Sclerosis Centers provided an efficient response to Covid-19 pandemic. • Multiple Sclerosis patients were satisfied of their Multiple Sclerosis Centers. • Longer disease duration reduced patients' satisfaction of Multiple Sclerosis Centers. • 1.3% of participants underwent a tele-health visit with specific tele-health software. • 80.1% of the sample believed that telehealth services should be improved in future. Covid-19 pandemic impacted on management of people with Multiple Sclerosis (pwMS). Level of satisfaction of pwMS regarding the care received by the staff of Multiple Sclerosis Centers (MSCs) during the pandemic was not fully investigated. In a large patient-centered multicenter study, the therapeutic adherence and quality of care of MSCs was assessed. In April–May 2021, an online survey was widespread by 16 Italian MSCs. Frequencies, percentages and/or means and standard deviations were calculated to describe the sample. ANOVAs were performed to evaluate the effect of sociodemographic and clinical variables on overall pwMS' rating of MSC assistance. 1670 pwMS completed the survey (67.3% women). During the pandemic, 88% did not change their disease modifying therapy schedule, and 89.1% reached their MSCs with no or little difficulties. Even if only 1.3% of participants underwent a tele-health follow-up visit with their MSC staff, the 80.1% believed that tele-health services should be improved regardless of pandemic. 92% of participants were satisfied of how their MSC took charge of their needs; ANOVAs revealed an effect of disease duration on pwMS' level of satisfaction on MSCs management during the pandemic. The results revealed an efficient MSCs response to Covid-19 pandemic and provided the basis for the implementing of tele-health services that would further improve the taking charge of patients, particularly those with longer disease, higher disability, and/or living far from their MSC. [ABSTRACT FROM AUTHOR]

Background The LMF1 (lipase maturation factor 1) gene encodes a protein involved in lipoprotein lipase and hepatic lipase maturation. Homozygous mutations in LMF1 leading to severe hypertriglyceridemia (SHTG) are rare in the literature. A few additional rare LMF1 variants have been described with poor functional studies. Objective The aim of this study was to assess the frequency of LMF1 variants in a cohort of 385 patients with SHTG, without homozygous or compound heterozygous deleterious mutations identified in lipoprotein lipase (LPL), apolipoprotein A5 (APOA5), apolipoprotein C2 (APOC2), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) genes, and to determine their functionality. Methods LMF1 coding variants were screened using denaturing high-performance liquid chromatography followed by direct sequencing. In silico studies of LMF1 variants were performed, followed by in vitro functional studies using human embryonic kidney 293T (HEK-293T) cells cotransfected with vectors encoding human LPL and LMF1 c DNA. LPL activity was measured in cell culture medium after heparin addition using human VLDL-TG as substrate. Results Nineteen nonsynonymous coding LMF1 variants were identified in 65 patients; 10 variants were newly described in SHTG. In vitro, p.Gly172Arg, p.Arg354Trp, p.Arg364Gln, and p.Arg537Trp LMF1 variants decreased LPL activity, and the p.Trp464Ter variant completely abolished LPL activity. We identified a young girl heterozygote for the p.Trp464Ter variant and a homozygote carrier of the p.Gly172Arg variant with a near 50% decreased LPL activity in vitro and in vivo. Conclusion The study confirms the rarity of LMF1 variants in a large cohort of patients with SHTG. LMF1 variants are likely to be involved in multifactorial hyperchylomicronemia. Partial LMF1 defects could be associated with intermittent phenotype as described for p.Gly172Arg homozygous and p.Trp464Ter heterozygous carriers. Highlights • LMF1 variants leading to SHTG are rare in literature. • We identified 19 LMF1 nonsynonymous coding variants in 385 patients with severeHTG. • Ten of these variants are newly described. • Five of these variants have a functional impact on LPL activity in vitro. • Functional variants in LMF1 contribute to the occurrence of SHTG. [ABSTRACT FROM AUTHOR]

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014–2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations. [ABSTRACT FROM AUTHOR]

We report the first case of an autoimmune hypertriglyceridemia successfully treated with rituximab, an anti-CD20-targeted monoclonal antibody. A 45-year-old man, with prior autoimmune conditions, developed severe, acquired hypertriglyceridemia resistant to traditional triglyceride lowering therapies. After the elimination of secondary or genetic causes, we detected the presence of anti-LPL-IgG by immunoblot. After 3 infusions of rituximab, we observed a marked improvement of his hypertriglyceridemia, concomitant with a reduction in plasma anti-LPL antibody titer and B-lymphocytes counts. The patient has been receiving rituximab maintenance therapy for 5 years without any serious adverse events and with excellent control of his previous, marked hypertriglyceridemia. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine if dental correction changes fecal fiber length (FFL) in horses that had never been subjected to dental treatments. Thirty adult horses with mild to moderate dental abnormalities were selected. Dental disorders noted included sharp enamel points, focal overgrowths, shear mouth, step mouth, wave mouth, accentuated transverse ridges, and diastema. The horses were confined to individual stalls and fed Tifton hay ( Cynodon spp.) 1.5% bwt/d, divided equally between two feedings. Fecal samples were taken for FFL analysis before (Day 0) and after (Day 15) dental correction. Mean FFL, determined by laboratory analysis, was recorded for each horse and time. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by T -test ( P < .05). Dental treatment resulted in significant ( P < .05) reductions in FFL, with mean ± standard deviation of 3.27 ± 2.27 mm before dental correction and 2.15 ± 1.29 mm after correction. The results suggest that dental treatment improved the mastication efficiency and that FFL can be used to assess the dental health of equines. [ABSTRACT FROM AUTHOR]

The acute-phase response (APR) is a rapid, nonspecific, systemic response occurring secondary to skeletal muscle damage and might be a protective physiological mechanism. The response has a number of components including increases in serum concentrations of the acute-phase proteins (APPs), which are primarily produced in the liver. This study was designed to evaluate the influence of marcha gait exercise on serum concentrations of the immunoglobulin A (IgA), immunoglobulin G (IgG), ceruloplasmin, transferrin, albumin (Alb), α 1 -antitripsin, haptoglobin (Hp), and α 1 -acid glycoprotein in 35 Mangalarga Marchador horses (18 geldings and 17 mares). The study also aimed to evaluate the differences between genders of the response to marcha gait exercise. Blood samples were assessed before and after official marcha contest. Acute-phase proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by Student-Newman-Keuls test ( P < .05). In both geldings and mares, APP concentrations did not increase in response to exercise. Significant differences of total serum protein concentration, Alb, Hp, IgA, and IgG between geldings and mares were noticed. In conclusion, this study provides evidence that marcha gait exercise performed during official contest is not intense enough to stimulate an APR, demonstrated by no change in serum concentrations of APPs in Mangalarga Marchador horses. The differences between genders in the present study warrant further investigation. [ABSTRACT FROM AUTHOR]

• Intra-articular injections of local anesthetics are a common in equine. • Lidocaine, bupivacaine, or saline 0.9% stimulates a local inflammatory response. • The local inflammatory response is more intense and lasting with lidocaine. • The acute phase protein identifies intra-articular inflammatory processes. The purpose of this study was to compare the extent of inflammation response in the middle carpal joints of healthy horses following intra-articular injection of 2% lidocaine, 0.5% bupivacaine, or 0.9% saline solution. The right middle carpal joint of 20 horses was injected with 5 mL of 0.5% bupivacaine (GB, n = 10) or 5 mL of 2% lidocaine (GL, n = 10). The left middle carpal joint of horses was used as a control (5 mL 0.9% saline). Serum and synovial fluid (SF) were aseptically collected before and at predetermined times after each injection. Serum and synovial fluid protein, albumin, transferrin, haptoglobin, ceruloplasmin, α1-antitripsin, and α1-acid glycoprotein concentrations were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared among treatments. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student–Newman–Keuls test (P <.05). Both lidocaine and bupivacaine induced serum and SF changes indicative of inflammation, but the magnitude of those changes was more pronounced for lidocaine. Administration of 0.9% saline also induced an inflammatory reaction, but the magnitude of these changes was less pronounced than those caused by GB and GL. The results suggested that bupivacaine is safer than lidocaine for intra-articular injection in horses. Saline solution should not be used as an adjunct to intra-articular injections in horses. [ABSTRACT FROM AUTHOR]

Summary Background & aims morbid obesity is associated with cardiovascular comorbidity. A noteworthy feature of this relationship could regard low levels of brain natriuretic peptide (BNP). The study investigates the relationship between BNP and obesity-related markers in a morbid obese population, along with echocardiographic and vascular parameters. Methods in 154 morbid obese patients we evaluated anthropometric parameters, glycometabolic/lipid profile, bioimpedentiometry, echocardiography, visceral fat area and flow-mediated dilation (FMD) by ultrasonography. Results we divided population in two groups on the basis of median BMI levels; patients with higher BMI had significantly lower BNP (p = .008), FMD (p = .014) and HDL-C (p = .001) and showed a more impaired heart function. A similar trend emerged subdividing patients on the basis of median visceral fat area. BNP showed a significant inverse correlation with BMI (p < .001), left ventricular mass (p = .026) and inter-ventricular septum thickness (p = .007) and a significant positive correlation with FMD (p = .008), HDL-C (p = .022), and ejection fraction (p = .013). BMI and triglycerides were independent predictors of BNP levels. Conclusions patients with higher BMI show lower BNP levels associated with greater total body fat amount. The correlation of BNP with endothelium-dependent vasodilation and cardiac impairment could represent another link between obesity and cardiovascular damage. [ABSTRACT FROM AUTHOR]

We report a new case of hypobetalipoproteinemia in a 44-year-old man of Peruvian origin exhibiting a heterozygous PCSK9 missense mutation (c.946 G>T, p. Gly316Cys). In vitro functional studies demonstrated that this mutation leads to a loss of function of PCSK9 on low-density lipoprotein receptor degradation. This patient exhibited liver steatosis; he was neither diabetic, nor obese or alcoholic, but is a carrier of 2 polymorphisms, p.Ile148Met (rs738409) and p.Glu167Lys (rs58542926) on PNPLA3 and TM6SF2 gene, respectively, previously shown to be associated with nonalcoholic steatosis and fibrosis evolution. These data suggested that if a resistance to hepatic steatosis mediated by the PCSK9 deficiency exists, as demonstrated in mice, it is not sufficient to prevent hepatic fatty accumulation in the case of genetic factors predisposing to nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

The marcha competition is a functional evaluation, without similar in the world. In this competition, the animals perform marcha at average speed between 9 and 12 km/hr for 50 minutes, covering roughly 6 to 7 km with no rest. The aim of this study was to evaluate and compare the effect of batida gait competition on acid–base balance in Mangalarga Marchador horses during an official marcha competition. The study was conducted on 24 Mangalarga Marchador horses, 12 stallions, and 12 mares (aged 4–6 years and 399 ± 45 kg of body weight). Venous blood samples were collected before and after competition. Blood samples were analyzed for acid–base balance, as well as biochemical and electrolyte parameters. In stallions, a significant ( P < .05) postexercise increase in pH, partial pressure of oxygen, bicarbonate concentration, base excess, and glucose was noted. Decrease ( P < .05) in p CO 2 (partial pressure of carbon dioxide), chloride and ionized calcium were observed after exercise only in stallions. No changes ( P > .05) in hematocrit, hemoglobin, sodium, and potassium were observed after exercise in all animals. The changes in the acid–base balance and electrolyte profile of the Mangalarga Marchador stallions after marcha competition resulted in hypochloremic metabolic alkalosis. Marcha competition did not cause acid–base disturbance in mares. This study enables an evaluation and comparison of physical effort caused by the marcha exercise on acid–base balance in Mangalarga Marchador horses and provides further evidence of the existence of gender differences in sports horses. [ABSTRACT FROM AUTHOR]

• Tramadol increases the threshold for mechanical stimulation similarly to lidocaine. • Tramadol promotes antinociceptive effect in ponies when administered to the distal alveolar nerve. • The antinociceptive effect of tramadol lasts longer than that of lidocaine. • The perineural administration of tramadol or lidocaine adjacent to the inferior alveolar nerve does not cause clinically significant changes. This study aimed to compare the antinociceptive effects of tramadol 5% and lidocaine 2% on mental nerve block in horses of the Brazilian Pony breed. Eight adult non-pregnant mares were used in this study. The ponies were tranquilized with acepromazine (5 µg kg−1, IV), and the infiltration of the mental foramen was performed in Treatment 1- tramadol 5% (T, 150 mg) or Treatment 2- lidocaine 2% (L, 60 mg), both at a total dose of 3 ml in each foramen. Heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), rectal temperature (RT), and formation of skin lesions (SL) were evaluated. Evaluation of nociception of the outer lip (OL), inner lip (IL), and gingiva (GG) were performed using an electronic von Frey device with the evaluation of the ponies' reactions to each stimulus. From these reactions, we determined latency time (LT) and duration of antinociception (DAN). Analysis of variance with 16 observations was performed for HR, RR, SAP, DAP, MAP, LT and DAN. Data were expressed as mean ± standard deviation and the means were compared by the SNK and Student's t-test (P < 0.05). Changes in HR, RR, SAP, DAP, and MAP between evaluation times were associated with the effects of acepromazine (P >0.05). No formation of skin lesions was observed. Latency time did not differ between treatments (P >0.05). Both lidocaine 2% and tramadol 5% produced an antinociceptive effect. We conclude that the duration of the antinociceptive effect of tramadol 5% is longer than that of lidocaine 2%. [ABSTRACT FROM AUTHOR]

• State and trait anxiety are highly prevalent in people with multiple sclerosis (PwMS). • State anxiety is more frequent among subjects with a recent MS diagnosis. • PwMS and clinically relevant state anxiety more often display MRI disease activity. • Trait anxiety is more prevalent among female PwMS with higher severity of fatigue. • Both state and trait anxiety are associated with higher depression severity. Anxiety represents one of the most prevalent psychiatric symptoms in multiple sclerosis (MS), impacting the overall disease burden and quality of life. This psychopathological feature can be expressed as state (S-ANX) and trait (T-ANX) anxiety, but few studies specifically evaluated these two components in MS. The present study was aimed at investigating the prevalence and specific correlates of S-ANX and T-ANX in a cohort of people with MS (PwMS). 88 in- and out-patients with MS were consecutively recruited. S-ANX and T-ANX were evaluated with the two subscales of the State and Trait Anxiety Inventory. Bivariate analyses were performed to compare PwMS who displayed clinically significant S-ANX and T-ANX and those who did not. Two logistic regression models were run in order to identify variables significantly associated with S-ANX and T-ANX. S-ANX and T-ANX presented a prevalence of 42% and 45.5%, respectively. S-ANX was more frequent in subjects hospitalized due to recent MS onset. PwMS and S-ANX more frequently had a recent relapse, as well as evidence of disease activity on brain magnetic resonance imaging. Subjects with T-ANX were more often females and displayed higher severity of fatigue. Depressive features at the Beck Depression Inventory were more severe in both S-ANX and T-ANX subjects. PwMS with S-ANX reported a higher prevalence of T-ANX and vice versa. At the logistic regressions, depression severity displayed a significant association with S-ANX and T-ANX. We also detected positive associations between S-ANX and inpatient status, as well as between T-ANX and female sex. Both S-ANX and T-ANX are highly prevalent features in PwMS. These two components of anxiety should be adequately identified and discriminated in the clinical practice. The higher severity of depression in PwMS with clinically significant anxiety should not be neglected. [ABSTRACT FROM AUTHOR]

Resumo O uso de ultrassom em anestesia regional permite visualizar a colocação da agulha e a propagação dos anestésicos locais. Nos últimos anos houve um grande interesse em determinar o volume mínimo eficaz de anestésico necessário para fazer a anestesia cirúrgica. A visualização precisa e em tempo real da difusão dos anestésicos locais com o uso de ultrassom pode ser o melhor requisito para reduzir a dose e os efeitos relacionados aos anestésicos locais. Revisamos uma série de estudos que relataram a eficácia de bloqueios guiados por ultrassom para reduzir o uso de anestésicos locais e obter anestesia cirúrgica, em comparação com bloqueios feitos com a técnica às cegas e de estimulação elétrica de nervos. Infelizmente, os resultados dos estudos são muito divergentes e não parecem indicar uma dose considerada eficaz para cada bloqueio de modo definitivo, mas é verdade que, com o auxílio do ultrassom, é possível reduzir a dose dos anestésicos em bloqueios. The ultrasound guidance in regional anesthesia ensures the visualization of needle placement and the spread of Local Anesthetics. Over the past few years there was a substantial interest in determining the Minimum Effective Anesthetic Volume necessary to accomplish surgical anesthesia. The precise and real‐time visualization of Local Anesthetics spread under ultrasound guidance block may represent the best requisite for reducing Local Anesthetics dose and Local Anesthetics‐related effects. We will report a series of studies that have demonstrated the efficacy of ultrasound guidance blocks to reduce Local Anesthetics and obtain surgical anesthesia as compared to block performed under blind or electrical nerve stimulation technique. Unfortunately, the results of studies are widely divergent and not seem to indicate a dose considered effective, for each block, in a definitive way; but it is true that, through the use of ultrasound guidance, it is possible to reduce the dose of anesthetic in the performance of anesthetic blocks. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether marcha exercise results in changes in serum hematologic and biochemical variables and whether this condition differs in male and female horses. Thirty-five Mangalarga Marchador horses, 18 males and 17 females were included in the study. Blood samples were obtained before and immediately after a marcha competition. Samples were used for measurement of hematocrit (HCT), hemoglobin concentration (HGB), red blood cell (RBC), total and differential white blood cell (WBC), total protein (TP), albumin (Alb), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), creatine kinase (CK), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Crea), and urea (BUN) levels. Data were submitted to analysis of variance using the SAS statistical program, and means were compared by the Tukey test ( P < .05). In both males and females, RBC, HCT, AST, and GGT activity increased in response to exercise, but there were no significant differences between genders. In females, significant increases in TP, BUN, Crea, CK, and LDH levels were detected after the marcha gait, but no such changes were detected in males. Total WBC concentrations increased in response to the exercise in both, males and females; however, there were no differences between genders. Plasma HGB, Alb, and ALP levels after marcha gait did not differ in both genders. Marcha exercise–induced significant hematologic and biochemical changes in serum of Mangalarga Marchador horses, independently of gender. However, females presented more blood changes after marcha gait. Gender differences should be taken into consideration in experiments with athletic horses. [ABSTRACT FROM AUTHOR]

Background Non-alcoholic fatty liver disease (NAFLD) is strongly related with enhanced morbidity and mortality from cardiovascular disease. In obese patients with both NAFLD and features of the metabolic syndrome, the cardiovascular risk is further increased. Aim The aim of this study is to investigate the relationship between severity of liver fibrosis evaluated by NAFLD fibrosis score (NAFLD-FS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), other obesity-related markers and preclinical atherosclerosis in morbidly obese patients with previously diagnosed NAFLD. Methods Laboratory parameters, visceral fat area (VFA), flow-mediated dilatation (FMD), intima-media thickness (IMT), HOMA-IR and NAFLD-FS were determined in 196 morbidly obese patients. Results Patients with higher NAFLD-FS or HOMA-IR show higher left max-IMT and lower FMD ( p < 0.001). VFA and NAFLD-FS, but not HOMA-IR, were independent predictors of reduced FMD (respectively β −0.268, p = 0.001 and β −0.165, p = 0.039, p of the model < 0.001) and increased left max-IMT (respectively β 0.165, p = 0.031 and β 0.301, p < 0.001, p of the model < 0.001). Conclusions In morbidly obese patients, NAFLD-FS correlates with markers of early vascular damage. NAFLD-FS, easier to obtain than VFA, seems to be a better score than HOMA-IR to categorize such subjects who are potentially at risk of future cardiovascular events. [ABSTRACT FROM AUTHOR]

Nothing to disclose. None. The Abetalipoproteinemia and Related Disorders Foundation (ABLRDF) is a nonprofit international organization established in 2019 comprised of patients with abetalipoproteinemia (ABL), familial hypobetalipoproteinemia (FHBL) and related hypobetalipoproteinemia disorders together with caregivers, researchers and medical professionals. To (i) underline ABLRDF's mission to increase awareness of ABL and other FHBL disorders, provide guidelines for lifelong medical care and facilitate access to specialized professionals, medical evaluations, and appropriate treatments; and (ii) highlight ABLRDF as an international medical advisory resource and advocate for improved access to affordable care. The patients and caregivers within ABLRDF performed non-scientific polling via Facebook to identify and prioritize health related concerns. An international panel of experts assembled to address these concerns, analyze the literature, and propose clinical guidelines. Initially, the panel was composed of two groups, which produced written descriptions for the hypobetalipoproteinemia disorders assigned to them. These versions were combined and all panel members then critically read and critiqued the final manuscript. (1) Several challenges faced by patients and caregivers were identified. First, physician awareness of monogenic hypobetalipoproteinemia disorders is suboptimal and contributes to a delay in diagnosis, resulting in substandard treatment and associated morbidities. Second, patient access to fat-soluble vitamins is often compromised by cost and/or inadequate insurance coverage. Third, published guidelines for the clinical management of hypobetalipoproteinemia disorders throughout the lifespan, including the peripartum period, are insufficient. (2)We classified monogenic hypobetalipoproteinemia into two subgroups based on the specific mechanisms that contribute to their disorders (Table 1). Class 1 disorders arise from defects in lipoprotein assembly and secretion. Class 2 disorders are due to enhanced lipoprotein catabolism. (3) We detailed the pathophysiology and clinical presentation of familial hypobetalipoproteinemia disorders and proposed guidelines for their lifelong management (Table 2). (4) Letters of medical necessity were submitted to insurance companies advocating coverage of fat-soluble vitamins for patients. The real-world experience of individuals within ABLRDF provides a closer examination of the unique struggle in managing these complex disorders while affording an opportunity to elevate the standard of medical care. We provide guidance in the identification and management of familial hypobetalipoproteinemia disorders with an aim to improve the health-related quality of life for patients. [ABSTRACT FROM AUTHOR]

Although perinatal complications during pregnancy in women with Congenital Heart Disease (ACHD) are well known, the pathophysiological mechanisms are still to be elucidated. As the placenta is the interface between mother and fetus, its analysis might help to better understand their interactions and identify risk factors for complications. We hypothesize that abnormal findings would be more frequent in placentas of women with CHD than in those without cardiac disease. The main objective of this study is to compare the incidence of placental abnormalities (PA) in ACHD versus controls women. The present proposal is to conduct a prospective, multicentric, national, 2-years (2023–2024) cohort study (research involving human type III), in order to analyze Doppler imaging and histological placentas, and compare findings in a group of women with ACHD versus a group without. The secondary objectives of the study are to assess the association between PA and the occurrence of maternal cardiovascular, fetal and/or perinatal complications, and to assess risk factors for PA or maternal/fetal events (Fig. 1). Placentas of ACHD would have significantly (P < 0.05) more abnormalities and these would correlate with the occurrence of complications. Description of PA could help to elucidate the pathophysiological mechanisms and eventually propose preventive therapeutic strategies of fetal and/or neonatal complications. Risk factors could be stratified according to the type of heart disease (as the mWHO score) and could allow to propose a novel risk-score of pregnancy in women with CHD. [ABSTRACT FROM AUTHOR]

The present work investigates the fracture toughness behaviour of Single Edge Notched Bending (SENB) samples of epoxy systems subject to water uptake aging. Two epoxy systems with a significantly different Glass Transition Temperature, T g , are in particular considered: a typical commercial non-aeronautical grade resin matrix for composite applications, reaching a T g of 90 °C, and a DGEBA+DDS epoxy system achieving a T g of 230 °C.The materials have been conditioned by hydrothermal aging in a thermal bath at the temperature of 50 °C. TransmissionPhotoelastic Stress Analysisis carried outon SENB samples during water aging, monitoring the presence and evolution of swelling stresses. The K IC Fracture toughness is measured and correlated with the internal stress field, with the water diffusion kinetics evaluated by gravimetric tests, and with the data from DMTA analyses. Results have highlighted significant differences in the fracture behaviour ofthe two epoxy systems. [ABSTRACT FROM AUTHOR]

Visual symptoms are a common clinical manifestation of multiple sclerosis (MS) and are frequently due to acute optic neuritis (ON). However, the entire visual pathway can be involved throughout the disease course. We describe the case of a young MS patient who experienced visual symptoms that were eventually found to be caused by retinal periphlebitis, an inflammatory process of the anterior visual pathway, which is common during MS, but rarely symptomatic. This case reinforces the concept that in all MS patients complaining visual symptoms, a complete work-up should be performed in order to rule out possible ON mimicries. [ABSTRACT FROM AUTHOR]

Pistons of IC engines are typically subjected during operation to high cycle fatigue loading cycles at high temperatures (up to 350°C) in areas facing the combustion chamber. During operation the high temperature exposure results in a progressive loss of fatigue strength of the material at the weakest areas of the piston and may eventually results in a premature failure by crack initiation and propagation. The quantification of the temperature effect on fatigue strength inevitably require experimentation since such data are scarce. An extensive fatigue testing program of eutectic Al-Si alloys at room temperature and at several high temperatures (250°C, 300°C and 350°C) is reported. Specimens were extracted from piston crowns and tested in a rotating bending test machine. The resulting fatigue strength loss at 107 cycles is quantified by a staircase approach. The influence of the test temperature is investigated in terms of chemical composition, process route and of mechanisms of fracture observed in the broken specimens. [ABSTRACT FROM AUTHOR]

Abstract: The present paper deals with identification of hydrocarbon sources in contaminated soil of three tank farms located in north, central and south Italy. Parent polycyclic aromatic hydrocarbons (naphthalene through benzo(g,h,i)perylene) and n-alkanes (n-C10 through n-C36) were determined. The study of source assignments was carried out by their distribution patterns, their diagnostic ratios, and determination of less-commonly used markers. The data show anthropogenic and biogenic origin of n-alkanes and petrogenic and pyrolytic sources of PAHs. Multiple sources of hydrocarbons, that were not considered in the preliminary environmental assessments, are identified. The application of a multi-criteria approach allows to locate petroleum pollution sources that affect the study sites. The results demonstrate that the application of a multi-criteria approach for source identification is a key point to assess environmental damage and prove that an accurate study of source identification has to be performed. The suggested methodology is a useful tool to manage contaminated sites and to plan appropriate interventions of clean up. [Copyright &y& Elsevier]

Abstract: Identifying tree growth releases is crucial to understand forest stand dynamics, their drivers (including climate change), and their interactions with other long-term ecosystem processes. We tested how bioclimate and geologic substrate affect the application of boundary line release criteria, which are based on scaling percent growth change to prior growth rate on a large number of samples, and then using a nonlinear function (e.g., negative exponential) to draw the maximum release potential (“boundary line”). Tree-ring series from 36 European beech (Fagus sylvatica L.) forests, comprising more than 130 thousand observations and spanning a range of elevations in the Italian Alps (200–1500m) and Apennines (400–1900m), were used to develop boundary lines for two geographical regions (Alps and Apennines) and three bioclimatic zones (high-mountain, mountain, low-elevation) within each region. In the Apennines, two distinct boundary lines were also developed for beech stands growing on sedimentary and volcanic soils. We uncovered different amounts of maximal growth releases for equal levels of prior growth when comparing the northern (central Europe) and southern (Italy) portion of the species’ geographic distribution. High elevation sites in the Apennines and the Alps had similar boundary lines, which in both cases remained well below the regional ones because of distinctly lower growth releases. A limiting effect of site fertility on growth releases was uncovered in the Alps for old-growth stands growing on poor soils (e.g. dolomite). To quantify the influence of bioclimate on growth releases we produced disturbance chronologies for the two oldest stands pertaining to the same bioclimatic zone according to regional and bioclimatic boundary lines. Moderate and major growth releases were severely underestimated when the regional boundary line was used rather than the one specifically computed for the bioclimatic zone. Since boundary lines were affected by biogeoclimate, reconstructing disturbance events from growth releases requires detailed analysis of tree growth records according to site conditions with special attention to extreme environments. [Copyright &y& Elsevier]