Neuroplasticity in Parkinson's disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, affecting millions of people and rapidly increasing over the last decades. Even though there is no intervention yet to stop the neurodegenerative pathology, many efficient treatment methods are available, including for patients with advanced PD. Neuroplasticity is a fundamental property of the human brain to adapt both to external changes and internal insults and pathological processes. In this paper we examine the current knowledge and concepts concerning changes at network level, cellular level and molecular level as parts of the neuroplastic response to protein aggregation pathology, synapse loss and neuronal loss in PD. We analyse the beneficial, compensatory effects, such as augmentation of nigral neurons efficacy, as well as negative, maladaptive effects, such as levodopa-induced dyskinesia. Effects of physical activity and different treatments on neuroplasticity are considered and the opportunity of biomarkers identification and use is discussed.

How to diagnose heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major healthcare problem that is raising in prevalence. There has been a shift in HpEF management towards early diagnosis and phenotype-specific targeted treatment. However, the diagnosis of HFpEF remains a challenge due to the lack of universal criteria and patient heterogeneity. This review aims to provide a comprehensive assessment of the diagnostic workup of HFpEF, highlighting the role of echocardiography in HFpEF phenotyping.

Health-Related Quality of Life in Romanian Patients with Dystonia: An Exploratory Study.

Background/Objectives: Dystonia is a neurological movement disorder characterized by involuntary muscle contractions that lead to abnormal movements and postures; it has a major impact on patients' health-related quality of life (HRQoL). The aim of this study was to examine the HRQoL of Romanian patients with dystonia using the EQ-5D-5L instrument. Methods: Responses to the EQ-5D-5L and the visual analogue scale (VAS) were collected alongside demographic and clinical characteristics. Health profiles were analyzed via the metrics of the EQ-5D-5L, severity levels, and age groups. Using Shannon's indexes, we calculated informativity both for patients' health profile as a whole and each individual dimension. Level sum scores (LSS) of the EQ-5D-5L were calculated and compared with scores from the EQ-5D-5L index and VAS. The HRQoL measures were analyzed through demographic and clinical characteristics. Descriptive statistics, Spearman correlation, and non-parametric tests (Mann-Whitney U or Kruskall-Wallis H) were used. The level of agreement between HRQoL measures was assessed using their intraclass correlation coefficient (ICC) and Bland-Altman plots. Results: A sample of 90 patients was used, around 75.6% of whom were female patients, and the mean age at the beginning of the survey was 58.7 years. The proportion of patients reporting "no problems" in all five dimensions was 10%. The highest frequency reported was "no problems" in self-care (66%), followed by "no problems" in mobility (41%). Shannon index and Shannon evenness index values showed higher informativity for pain/discomfort (2.07 and 0.89, respectively) and minimal informativity for self-care (1.59 and 0.68, respectively). The mean EQ-5D-5L index, LSS, and VAS scores were 0.74 (SD = 0.26), 0.70 (SD = 0.24), and 0.61 (SD = 0.21), respectively. The Spearman correlations between HRQoL measures were higher than 0.60. The agreement between the EQ-5D-5L index and LSS values was excellent (ICC = 0.970, 95% CI = 0.934-0.984); the agreement was poor-to-good between the EQ-5D-5L index and VAS scores (ICC = 683, 95% CI = 0.388-0.820), and moderate-to-good between the LSS and VAS scores (ICC = 0.789, 95% CI = 0.593-0.862). Conclusions: Our results support the utilization of the EQ-5D-5L instrument in assessing the HRQoL of dystonia patients, and empirical results suggest that the EQ-5D-5L index and LSS measure may be used interchangeably. The findings from this study highlight that HRQoL is complex in patients with dystonia, particularly across different age groups.

Diagnosing diastolic dysfunction and heart failure with preserved ejection fraction in patients with atrial fibrillation: a clinical challenge.

Left ventricular (LV) diastolic dysfunction, atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) share common risk factors and are closely related to each other and to adverse cardiovascular events. Exertional dyspnea in patients with AF should trigger comprehensive LV diastolic function evaluation since AF frequently precedes incident HFpEF. Echocardiographic assessment of LV diastolic function in patients with AF is challenging, mainly because of variability in cycle length, the absence of atrial contraction, and the frequent occurrence of LA enlargement regardless of LV filling pressures (LVFP). The algorithm of the 2016 recommendations for the evaluation of LV diastolic function cannot be directly applied in this setting. This review discusses the modalities available for diastolic function assessment and HFpEF diagnosis in patients with AF. Based on currently available data, a reasonable clinical target of diastolic function evaluation in AF would be to reach a binary conclusion: LVFP elevated or not. Recently, a two-step algorithm that combined several echocardiographic parameters plus inclusion of body mass index, has been proposed to differentiate normal from elevated LVFP in patients with AF. The echocardiographic evaluation must be complemented by a thorough clinical evaluation along with natriuretic peptides and cardiac catheterization in selected cases. If a diagnosis of HFpEF cannot be ascertained, a close follow up for timely identification of diastolic dysfunction markers along with monitoring and correction of modifiable risk factors are recommended.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación / Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes

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Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms.

AIMS: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. METHODS AND RESULTS: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CONCLUSIONS: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

Left main coronary artery compression in precapillary pulmonary hypertension.

Pulmonary hypertension (PH) is a progressive and invalidating condition despite available therapy. Addressing complications such as left main coronary artery compression (LMCo) due to the dilated pulmonary artery (PA) may improve symptoms and survival. Nevertheless, clear recommendations are lacking. The aim of this study is to analyze the prevalence, characteristics, predictive factors and impact of LMCo in a heterogenous precapillary PH population in a single referral center. Two hundred sixty-five adults with various etiologies of precapillary PH at catheterization were reviewed. Coronary angiography (CA) was performed for LMCo suspicion. Revascularization was performed in selected cases. Outcomes were assessed at a mean follow-up of 3.9 years. LMCo was suspected in 125 patients and confirmed in 39 (31.2%), of whom 21 (16.8%) had 50%-90% stenoses. Nine revascularizations were performed, with clinical improvement. The only periprocedural complication was a stent migration. LMCo was associated with PH etiology (p 0.003), occuring more frequently in congenital heart disease-associated PH (61.5% of all LMCo cases, 66.6% of LMCo ≥ 50%). Predictors of LMCo ≥50% were PA ≥ 37.5 mm (Sn 81%, Sp 74%) and PA-to-aorta ≥1.24 (Sn 81%, Sp 69%), with increased discrimination when considering RV end-diastolic area. LMCo ≥ 50% without revascularization presented clinical deterioration and worse survival (p 0.019). This analysis of a heterogeneous pre-capillary PH population provides LMCo prevalence estimation, predictive factors (PA size, PA-to-aorta, RV end-diastolic area and PH etiology) and long-term impact. While LMCo impact on survival is inconclusive, untreated LMCo ≥ 50% has worse prognosis. LMCo revascularization may be performed safely and with good outcomes.

Cohort profile: the European Unified Registries On Heart Care Evaluation and Randomized Trials (EuroHeart)-acute coronary syndrome and percutaneous coronary intervention.

AIMS: The European Unified Registries On Heart Care Evaluation and Randomized Trials (EuroHeart) aims to improve the quality of care and clinical outcomes for patients with cardiovascular disease. The collaboration of acute coronary syndrome/percutaneous coronary intervention (ACS/PCI) registries is operational in seven vanguard European Society of Cardiology member countries. METHODS AND RESULTS: Adults admitted to hospitals with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are included, and individual patient-level data collected and aligned according to the internationally agreed EuroHeart data standards for ACS/PCI. The registries provide up to 155 variables spanning patient demographics and clinical characteristics, in-hospital care, in-hospital outcomes, and discharge medications. After performing statistical analyses on patient data, participating countries transfer aggregated data to EuroHeart for international reporting. Between 1st January 2022 and 31st December 2022, 40 021 admissions (STEMI 46.7%, NSTEMI 53.3%) were recorded from 192 hospitals in the seven vanguard countries: Estonia, Hungary, Iceland, Portugal, Romania, Singapore, and Sweden. The mean age for the cohort was 67.9 (standard deviation 12.6) years, and it included 12 628 (31.6%) women. CONCLUSION: The EuroHeart collaboration of ACS/PCI registries prospectively collects and analyses individual data for ACS and PCI at a national level, after which aggregated results are transferred to the EuroHeart Data Science Centre. The collaboration will expand to other countries and provide continuous insights into the provision of clinical care and outcomes for patients with ACS and undergoing PCI. It will serve as a unique international platform for quality improvement, observational research, and registry-based clinical trials.

A Review and Comparative Analysis of Transoral Surgical Treatment versus Conservative Management in Early-Stage Oropharyngeal Cancer.

INTRODUCTION: Oropharyngeal cancer requires a comprehensive evaluation of treatment options, including surgery, radiation therapy, and chemotherapy. It is crucial to customize these treatments based on the stage of the tumor and the overall health of the patient, enabling personalized or combined approaches. Transoral surgical techniques have regained popularity due to the advancements and limitations of non-surgical strategies. The potential influence of surgical procedures on patients' quality of life highlights the need for careful intervention selection; among them, the transoral approach has proven to be especially beneficial for early-stage oropharyngeal neoplasms. METHODS: To explore potential treatments for early-stage oropharyngeal malignancies, this study carefully reviews the literature, using information from papers, current research, and global databases. The review protocol commenced on November 2023. A comprehensive search of the PUBMED database was undertaken, employing pertinent terms associated with oropharyngeal, transoral surgery or radiotherapy, robotic surgery, and chemotherapy. RESULTS: Treating early-stage oropharyngeal neoplasms is particularly intriguing due to the multitude of variables influencing treatment decisions, leading to ongoing debates in specialized literature. Regardless of the chosen approach, maintaining a high quality of life is crucial. To assess this, standardized questionnaires from the European Organization for Research and Treatment of Cancer were employed, revealing superior outcomes for patients solely undergoing surgical intervention. Additionally, in the realm of specialized literature, cases of HPV-positive oropharyngeal neoplasms are recognized for their heightened radiosensitivity and more favorable long-term prognosis. CONCLUSIONS: Surgical intervention and radiotherapy are the main treatment options for oropharyngeal cancer, and they can be used separately or together for maximum effectiveness. Amid ongoing discussions, determining the superior effectiveness between the two options continues to be a matter of debate. This study provides a comprehensive analysis, offering valuable perspectives for future discussions. Neoplasm in the oropharynx can be effectively treated using transoral microsurgery.

Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry.

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.

Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

BACKGROUND: For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. STUDY QUESTION: What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? STUDY DESIGN: A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. MEASURES AND OUTCOMES: Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. RESULTS: At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. CONCLUSIONS: These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Pulsatile Femoral Vein Doppler Pattern is a Parameter of Venous Congestion in ICU Patients.

OBJECTIVES: The aim of this study was to evaluate if the presence of a pulsatile femoral vein pattern is an indicator of venous congestion in the intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Three medico-surgical university-affiliated ICUs. PARTICIPANTS: Adult patients who had an ultrasound evaluation at several time points during their ICU stay: at baseline (within 24 hours of admission to ICU), daily during their ICU stay, and within 24 hours before ICU discharge. INTERVENTIONS: At each time point, the hemodynamic, respiratory, and cardiac ultrasound parameters were recorded. The common femoral vein was studied with pulsed-wave Doppler at the level of the femoral trigonum, with high frequency (5-13 MHz) linear array vascular probe and venous vascular mode, in supine patients. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients who underwent 400 ultrasound evaluations (3.7 ± 1 ultrasound evaluations per patient) during their ICU stay were included. Seventy-nine of 108 patients (73%) had a pulsatile femoral vein pattern at least at 1 time point. The multivariable mixed effects logistic regression model demonstrated an association among pulsatile femoral vein pattern, body mass index (OR: 0.91[95% CI 0.85-0.96], p = 0.002), inferior vena cava mean diameter (OR: 2.35 [95% CI 1.18-4.66], p = 0.014), portal vein pulsatility (OR: 2.3 [95% CI 1.2-4.4], p = 0.012), and congestive renal vein flow pattern (OR: 4.02 [95% CI 2.01-8.03], p < 0.001). The results were confirmed by principal component analysis. CONCLUSION: In the ICU, a pulsatile femoral vein pattern is associated with parameters of venous congestion, independently of the patient's volume status, and ventilatory treatment. These results suggest the femoral vein Doppler pulsatility as a parameter of congestion in ICU patients.

PFO-spectrum disorder: two different cerebrovascular diseases in patients with PFO as detected by AI brain imaging software.

Background: Patent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions. Patients and methods: Retrospective, case-control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume. Results: Of the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03-0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02-0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes. Discussion: We suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and "silent" WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the "at-risk" PFOs and gain deeper insights into their clinical implications.

Tricuspid regurgitation: Frequency, clinical presentation, management and outcome among patients with severe left-sided valvular heart disease in Europe. Insights from the ESC-EORP Valvular Heart Disease II survey.

AIMS: Tricuspid regurgitation (TR) is commonly observed in patients with severe left-sided valvular heart disease (VHD). This study sought to assess TR frequency, management and outcome in this population. METHODS AND RESULTS: Among 6883 patients with severe native left-sided VHD or previous left-sided valvular intervention enrolled in the EURObservational Research Programme prospective VHD II survey, moderate or severe TR was very frequent in patients with severe mitral VHD (30% when mitral stenosis, 36% when mitral regurgitation [MR]), especially in patients with secondary MR (46%), and rare in patients with severe aortic VHD (4% when aortic stenosis, 3% when aortic regurgitation). An increase in TR grade was associated with a more severe clinical presentation and a poorer 6-month survival (p < 0.0001). Rates of concomitant tricuspid valve (TV) intervention at the time of left-sided heart valve surgery were high at the time of mitral valve surgery (50% when mitral stenosis, 41% when MR). Concordance between class I indications (patients with severe TR) for concomitant TV surgery at the time of left-sided valvular heart surgery according to guidelines and real-practice decision-making was very good (88% overall, 95% in patients operated on for MR). CONCLUSION: In this large international prospective survey among patients with severe left-sided VHD, moderate/severe TR was frequent in patients with mitral valve disease and was associated with a poorer outcome as TR grade increased. In patients with severe TR, compliance to guidelines for class I indications for concomitant TV surgery at the time of left-sided heart valve surgery was very good.

[Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes]. / Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación.

This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis.

Multiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosis and management of MM. The main purpose of this study is to determine whether NGS, in addition to cytogenetics, can influence risk stratification and management. Additionally, we aim to establish whether mutational analysis of the CD138 cell population is a suitable option for the characterization of MM compared to the bulk population. Following the separation of the plasma cells harvested from 35 patients newly diagnosed with MM, we performed a FISH analysis to detect the most common chromosomal abnormalities. Consecutively, we used NGS to evaluate NRAS, KRAS, BRAF, and TP53 mutations in plasma cell populations and in bone marrow samples. NGS data showed that sequencing CD138 cells provides a more sensitive approach. We identified several variants in BRAF, KRAS, and TP53 that were not previously associated with MM. Considering that the presence of somatic mutations could influence risk stratification and therapeutic approaches of patients with MM, sensitive detection of these mutations at diagnosis is essential for optimal management of MM.

European Society of Cardiology Quality indicators for the care and outcomes of adults undergoing transcatheter aortic valve implantation.

BACKGROUND AND AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing transcatheter aortic valve intervention (TAVI). METHODS: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. Key domains were identified by constructing a conceptual framework for the delivery of TAVI care. A list of candidate QIs were developed by conducting a systematic review of the literature. A modified Delphi method was then used to select the final set of QIs. Finally, we mapped the QIs to the EuroHeart Data Standards for TAVI to ascertain the extent to which the EuroHeart TAVI registry captures information to calculate the QIs. RESULTS: We formed an international group of experts in quality improvement and TAVI, including representatives from the European Association of Percutaneous Cardiovascular Interventions, the European Association of Cardiovascular Imaging and the Association of Cardiovascular Nursing & Allied Professions. In total, 27 QIs were selected across eight domains of TAVI care, comprising 22 main (81%) and five secondary (19%) QIs. Of these, 19/27 (70%) are now being utilised in the EuroHeart TAVI registry. CONCLUSION: We present the 2023 ESC QIs for TAVI, developed using a standard methodology and in collaboration with ESC Associations. The EuroHeart TAVI registry allows calculation of the majority of the QIs, which may be used for benchmarking care and quality improvement initiatives.

Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb. Seeking alternatives, physical polysaccharide hydrogels emerge as promising candidates due to their tunable physicochemical and biodegradability features. Unfortunately, none have demonstrated simultaneous biocompatibility, biodegradability, and controlled release properties for large proteins (≥150 kDa) after SC delivery in clinical settings. Here, a novel two-component hydrogel comprising chitosan and chitosan@DOTAGA is introduced that can be seamlessly mixed with sterile mAbs formulations initially designed for intravenous (IV) administration, repurposing them as novel tunable SC formulations. Validated in mice and nonhuman primates (NHPs) with various mAbs, including trastuzumab and rituximab, the hydrogel exhibited biodegradability and biocompatibility features. Pharmacokinetic studies in both species demonstrated tunable controlled release, surpassing the capabilities of rHuPH20, with comparable parameters to the rHuPH20+mAbs formulation. These findings signify the potential for rapid translation to human applications, opening avenues for the clinical development of this novel SC biosimilar formulation.