Clinical Status Research Articles

Overview of the Current Advancements and Trends in the Transungual Drug Delivery System

Background: Drug delivery across human nails is termed a transungual drug delivery system. It is recommended for the amelioration of nail disorders and infectious nail diseases like onychomycosis. Thereby, vivid anti-fungal regimens have been prescribed in the form of different types of formulations, including nail lacquers, nail film, nail paint, and other types for treating onychomycosis. Method: All the formulations currently marketed or being marketed for the transungal drug delivery system were thoroughly studied, compared, and evaluated for their advantages and disadvantages so that a new vision can be sustained along the path of creating newer anti-fungal transunguals, keeping in mind the anatomy of the nail and various parameters that govern bioavailability of active pharmaceutical ingredients across the nail bed. Accordingly, different techniques are devised to enhance permeation across the nail. The various parameters used to evaluate these formulations depend upon their physical, chemical, and mechanical properties. Conclusion: The recent approaches in transungual novel drug delivery systems have been reported while exemplifying a few patented and marketed formulations, along with the clinical trial status of these formulations. There is a need for the development of new techniques to overcome all the loopholes present in the ongoing treatment techniques and the formulations used nowadays for the treatments of diseases that occur in nails. After thoroughly detailing transungal novel drug delivery systems, we envisage great opportunities for the researchers to carry out novel work in chemotherapy through nails.

A Phase 3, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Moderate COVID-19.

Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value<30 and symptom onset within 4days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct≥30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p=0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p=0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Clinical and Imaging Characteristics, Care Pathways, and Outcomes of Traumatic Epidural Hematomas: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery. This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling. In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died. Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.

Clinical status and future prospects of neoadjuvant immunotherapy for localized mismatch repair-deficient cancers: a review.

Frameshift mutations accumulate in cancers related to mismatch repair deficiency (dMMR), which has the potential to produce various neoantigens, representing a distinct subset of cancers that respond considerably to immunotherapy. In recent years, robust evidence has supported the first-line application of immunotherapy for patients with metastatic dMMR cancers, which provoked extensive investigations of the feasibility and efficacy of immunotherapy in the up-front settings, including neoadjuvant therapy. Several completed trials with small sample sizes suggested that neoadjuvant immunotherapy can achieve an impressively high complete response rate, for the first time offering the potential of systemic therapy to cure cancer without the need for surgical resection. However, a difficult dilemma emerges, clinicians are now facing selection between the standard of care with well evidence for proficient MMR but suboptimal for dMMR cancers and the emerging immunotherapy with promising results but only based on a limited number of patients with shorter duration of follow-up. This review aims to provide a comprehensive summary for biological rationale and clinical status of neoadjuvant immunotherapy in patients with dMMR cancers. Furthermore, I elaborate on particular issues that must be taken into consideration for further advancement in the field.

Health and wellbeing status of the long-lived individuals of the Spanish LONGECYL cross-sectional study

BackgroundThe increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain.MethodsA sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals’ health status. The significant level for the bivariate analysis was established at 0.05.ResultsPerceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 [2,32-27.41]) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 [1.40–4.29]). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence.ConclusionThe long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.

Big data and its impact on the 3Rs: a home cage monitoring oriented review

Undisturbed home cage recording of mouse activity and behavior has received increasing attention in recent years. In parallel, several technologies have been developed in a bid to automate data collection and interpretation. Thanks to these expanding technologies, massive datasets can be recorded and saved in the long term, providing a wealth of information concerning animal wellbeing, clinical status, baseline activity, and subsequent deviations in case of experimental interventions. Such large datasets can also serve as a long-term reservoir of scientific data that can be reanalyzed and repurposed upon need. In this review, we present how the impact of Big Data deriving from home cage monitoring (HCM) data acquisition, particularly through Digital Ventilated Cages (DVCs), can support the application of the 3Rs by enhancing Refinement, Reduction, and even Replacement of research in animals.

Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis

The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.

Analysis of clinical outcomes in older individuals who received pharmaceutical care and posthospital discharge follow-up.

Previous evidence underscores the need to assess potential clinical outcomes resulting from pharmaceutical care interventions and to monitor patient's progress to evaluate their clinical evolution, which is crucial for bolstering the relevance of implementing pharmaceutical care in healthcare services. To conduct an in-depth analysis of pharmaceutical care practices in a geriatric ward and monitor the clinical outcomes of older people served. This interventionist study was conducted in the geriatrics ward of a Brazilian university hospital. The research intervention occurred between January and May 2022, with a follow-up conducted for up to 90 days after patients' hospital discharge. Older patients in the geriatrics ward received pharmaceutical care, including medication reconciliation, medication review,and pharmacotherapeutic follow-up, aimed at identifying and resolving drug-related problems (DRPs). The clinical relevance of DRPs and pharmaceutical recommendations was evaluated. Additionally, analyses were conducted on mortality and rehospitalization outcomes in older patients at 30, 60,and 90 days following initial hospital discharge. Of the patients evaluated, a significant 88.3% exhibited at least one DRP (with an average of 2.6 ± 1.9 DRPs per patient), with the majority classified as need/indication problems (38.9%). The acceptance rate of pharmaceutical recommendations was 80.9%, with the majority categorized as very significant relevance (60.4%). DRPs were predominantly of serious clinical relevance (50.9%). In patients whose clinical indicators could be monitored, 95.5% showed some clinical response (in vital signs, laboratory testsand/or clinical status evolution) potentially related to resolved DRPs. Association analysis revealed that a higher number of medications in use before hospitalization correlated with a greater identification of DRPs during hospitalization (p = 0.03). At hospital discharge, 23.6% of patients were no longer using polypharmacy. In total, 16 patients (26.7%) died during the study period. Among patients who did not die during hospitalization (n = 54), 20 patients (37%) experienced rehospitalizations within 90 days following discharge. This study facilitated the consolidation of pharmaceutical care implementation in a geriatric ward. We conducted identification, evaluation,and proposed evidence-based solutions, as well as monitored cases for outcome analysis. It is anticipated that this methodology will inspire future research and the implementation of pharmaceutical care-related services.

Neoadjuvant Chemotherapy Does Not Improve Survival in cT2N0M0 Gastric Adenocarcinoma Patients: A Multicenter Propensity Score Analysis.

According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences. The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients. A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups. Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7±12.8 vs. 69.8±12.1 years for S patients; p<0.001) and had a better health status (World Health Organization performance status=0 in 60.3% of CS patients vs. 34.5% of S patients; p=0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW (p=0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p=0.42), as was 5-year DFS (70.4% vs. 68.5%; p=0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW. Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone.

Transcription Decisions of Conjoined Independent Clauses Are Equitable Across Dialects but Impact Measurement Outcomes.

Transcription of conjoined independent clauses within language samples varies across professionals. Some transcribe these clauses as two separate utterances, whereas others conjoin them within a single utterance. As an inquiry into equitable practice, we examined rates of conjoined independent clauses produced by children and the impact of separating these clauses within utterances on measures of mean length of utterance (MLU) by a child's English dialect, clinical status, and age. The data were archival and included 246 language samples from children classified by their dialect (African American English or Southern White English) and clinical status (developmental language disorder [DLD] or typically developing [TD]), with those in the TD group further classified by their age (4 years [TD4] or 6 years [TD6]). Rates of conjoined independent clauses and the impact of these clauses on MLU varied by clinical status (DLD < TD) and age (TD4 < TD6), but not by dialect. Correlations between the rate of conjoined clauses, MLU, and language test scores were also similar across the two dialects. Transcription decisions regarding conjoined independent clauses within language samples lead to equitable measurement outcomes across dialects of English. Nevertheless, transcribing conjoined independent clauses as two separate utterances reduces one's ability to detect syntactic differences between children with and without DLD and document syntactic growth as children age. https://doi.org/10.23641/asha.25822675.

Evaluation of CSF 8-iso-prostaglandin F2α and erythrocyte anisocytosis as prognostic biomarkers for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a serious, life-threatening, complication affecting patients who have survived the initial bleeding from a ruptured intracranial aneurysm. Due to the challenging diagnosis, potential DCI prognostic markers should be of value in clinical practice. According to recent reports isoprostanes and red blood cell distribution (RDW) showed to be promising in this respect. We conducted a prospective study of 27 aSAH patients and control group (n = 8). All patients from the study group were treated within the first day of the initial bleeding. We collected data regarding clinical status and results of biochemical, and radiological examinations. We measured cerebrospinal fluid (CSF) concentration of 8-iso-prostaglandin F2α (F2-IsoP) and RDW on days 1, 3, and 5. Both CSF F2-IsoP level and RDW-SD measured on day 1 were significant predictors of DCI. The receiver operating characteristics curve for DCI prediction based on the multivariate model yielded an area under the curve of 0.924 (95% CI 0.824–1.000, p < 0.001). In our study, the model based on the combination of RDW and the level of isoprostanes in CSF on the first day after the initial bleeding showed a prognostic value for DCI prediction. Further studies are required to validate this observation.

Assessment of the Effectiveness and Safety of Wheelchair Use Training for Patients with Hemiparesis

INTRODUCTION. The rationale of the research is defined by the large number of patients with hemiparesis, unable to restore an upright posture and in need of training to use a wheelchair. AIM. To present the methodology of wheelchair training of patients with hemiparesis. MATERIALS AND METHODS. We observed 30 patients with severe hemiparesis during wheelchair training. Examination included assessment of clinical, neurological, and mental status (MMSE — Mini-Mental State Examination), testing of limb muscle strength according to Lovett’s scale modified by L.D. Potekhin, level of sitting function compensation assessment, wheelchair skills (Wheelchair Skills Test). Each patient attended 10 wheelchair training sessions and related physical therapy (PT) sessions, with PT classes preceding the wheelchair training sessions and practicing the wheelchair-using movements required in the wheelchair training sessions. Patients controlled the wheelchair using only healthy limbs. RESULTS. At the moment of admission, 14 patients were not able to use wheelchair independently; 16 patients were able to use wheelchair to varying degrees. As a result of the sessions, the muscle strength of healthy limbs increased; statistically significant improvement in sitting and wheelchair skills was noted. None of the patients who scored 10 for MMSE test improved their wheelchair skills. CONCLUSION. Persons with severe hemiparesis learn to use the wheelchair with the help of healthy limbs. Physical therapy sessions precede wheelchair training and form the movements necessary for learning to use the wheelchair.

Do Acoustic Characteristics of Dysarthria in People With Parkinson's Disease Differ Across Languages?

Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls). French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive.

MANAGEMENT OF REMOTE MONITORING FOR IMPLANTABLE DEVICES CONTROLS: SINGLE CENTER EXPERIENCE

Abstract Background Nowadays the benefits of remote monitoring (RM)of cardiac implantable electronic devices (CIEDs) are Known: an improved both device surveillance and patient clinical management and a decrease in office follow up. So RM is used as supplement in clinic follow up for patients with CIED.However despite decades to RM utilization there are challenges in managing patients with RM including large number of trasmissions and lack of trained staff. There are many different model of care to RM management. Methods We describe our model of care to management CIED recipients with RM considering data collected from January 2021 to November 2023. Results Our model of care consists of 4 electrophysiologists Physicians and 4 Tecnicians. RM enrollment is performed at scheduled in office visit after ten days from hospital discharge after device implantation. implantable cardiac device(ICD)recipients with RM are annualy followed in office and biennal for pacemaker (PM) recipients and they send every three months transmissions. Trained tecnicians gives home monitor, take care of patients education and collected and screen transmissions. Tecnicians inform immediately physicians in case of urgent alert (shock or antitachicardia pacing therapy (ATP), sustained ventricular tachycardia(TV), ventricular fibrillation (Fv) indicator of elective replacement (ERI), lead releted alert or noise). Physician contact patients the same day (exept Saturday and Sunday). In addiction Physicians twice a week review less urgent and scheduled transmissions and call the patients by phone for visit in office for patients with low rate of biventricular pacing, detection of atrial fibrillation. We have 1000 patients with RM: 746 ICD recipients (103 Biotronik, 150 Abbott, 200 Boston scientific, 293 medtronic), 50 implantable cardiac monitor (ICM) recipients and 204 PM recipients. We analyze 12721 transmissions.Considering ICD recipient we detect 96 episode of ATP and 31 of shock. Shock of ICD was registered in 52 patients (6,9%)We received 1982 atrial fibrillation (AF) detection, with 35 for new detectable AF.The most of transmisisone were for low bIV pacing. We contacted these patients by phone about clinical status and in some case we called them in office. Conclusions Our model of care allows to control a large number of trasmissions with fast management of urgent alert trasmissions.

PERCUTANEOUS CORRECTION OF "BADLY ACCOMPANIED" MASSIVE TRICUSPID REGURGITATION

Abstract Background Tricuspid regurgitation (TR) is a common valvular pathology that impairs quality of life and survival. Tricuspid transcatheter edge–to–edge repair (t–TEER) has shown promising potential in the TR treatment. There remains several uncertainties such as timing of intervention in relation to clinical status, RV function, pulmonary artery pressure and many comorbidities that are often overlooked. Case Summary A 80–year–old man with dilated cardiomyopathy, persistent atrial fibrillation and biventricular defibrillator (ICD), was admitted to our centre for congestive heart failure (CHF). Echocardiography showed massive TR, severe right heart dilatation, increased systolic pulmonary artery pressure, severely dilated inferior vena cava (IVC) and hepatic veins with systolic flow reversal. We also found an uncommonly high blood flow coming to the right atrium from the IVC, due to an anomalous vascular communication between an intrahepatic portal branch and a hepatic vein, a so–called intrahepatic portosystemic venous shunt (IPSVS). Although these relatively rare shunts are usually not treated unless symptomatic, after a collective careful evaluation, we decided to proceed to the embolization of the IPSVS with a vascular plug, to make the t–TEER less challenging, safer and more durable. In better general conditions, after 2 months, the patient underwent the transcatheter tricuspid procedure with a single XTW TriClip™ (Abbott). At 3 months follow–up, the patient showed noticeable improvements in QoL, CHF signs and symptoms, echocardiographic parameters and exercise capacity. Discussion Appropriate timing of t–TEER is crucial not only to avoid irreversible RV damage and organ failure, but also to increase the success rate of the procedures. In this case we observed that the IPSVS treatment contributed significatively to improve the patient’s clinical status and to reduce the right heart volume overload before attempting the t–TEER. This combined approach facilitated the technical success of tricuspid procedure, that was itself challenging due to the ICD leads in the right chambers. Conclusion Patients’ selection and timing of percutaneous TR treatment are not clearly defined. This case shows that a winning strategy to approach challenging TR is to solve, before the tricuspid treatment, all the potentially treatable comorbidities that could negatively interfere with the technical success of the procedure itself and with the durability of TR reduction.

Sustained Effectiveness and Safety Over Time of Teriflunomide in Chinese Patients with Relapsing Multiple Sclerosis in the Greater Bay Area of China: Insights from Real-World Data.

The real-world data on the medium- to long-term effectiveness and safety of teriflunomide in Chinese patients with relapsing multiple sclerosis (MS) is limited. Therefore, this study aims to assess the treatment outcomes of teriflunomide in Chinese patients with MS over a medium- to long-term period. This cohort study was carried out in three tertiary hospitals and regional MS centers located in the Greater Bay Area of China. We obtained the historical clinical data of patients who underwent teriflunomide treatment for at least 6months. The primary objective was to evaluate the proportion of patients achieving no evidence of disease activity (NEDA)-3 status, which is characterized by the absence of relapses, confirmed disability worsening, and new or enlarging MRI lesions, over time. Secondary objectives included assessing the proportion of patients meeting each NEDA-3 criterion, changes in motor and cognitive function, as well as the incidence of adverse events and treatment discontinuations. A total of 160 patients with MS were enrolled, including 125 patients treated with teriflunomide for at least 1year (≥ 1-year completers) and 71 patients treated for at least 2years (≥ 2-year completers). A total of 85.63% of the overall population achieved clinical NEDA-3 status at 6months of teriflunomide treatment, and 71.20% of ≥ 1-year completers achieved NEDA-3 status at 12months of teriflunomide treatment. The median timed 25-foot walk test (T25FW), nine-hole peg test (9-HPT), and paced auditory serial addition test (PASAT) results were relatively stable before and after treatment. Medium- to long-term MS disease activity, as indicated by NEDA-3 status, is well controlled in patients treated with continuous teriflunomide treatment in real-world settings.

Altered cerebrospinal fluid neurofilament light chain but not neurogranin levels are associated with response to ocrelizumab treatment in relapsing remitting multiple sclerosis: a preliminary study.

Ocrelizumab is a CD20-targeting monoclonal antibody used for treatment of multiple sclerosis (MS). Serum and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels are reduced in MS patients under ocrelizumab treatment indicating a preventive action against neuro-axonal degeneration. Our aim, in this preliminary study, was to explore the impact of ocrelizumab treatment on synaptic integrity through assessment of neurogranin levels. Thirteen relapsing-remitting multiple sclerosis (RRMS) patients resistant to first-line immunomodulating agents were enrolled and followed up for 24 months under ocrelizumab treatment. Disease activity was monitored by periodic EDSS, MSSS and cranial-spinal MRI assessments. No evidence of disease (NEDA)-3 activity was determined and CSF levels of NFL (marker of neuro-axonal integrity) and neurogranin (marker of synaptic integrity) were measured by ELISA at baseline and 12-month ocrelizumab treatment. Seven RRMS patients, who preserved NEDA-3 status during 24-month follow-up showed ≥30% NFL level decrease, whereas six patients with stable/increased NFL levels displayed relapse, MRI lesion or disability progression. Although most RRMS patients exhibited increased CSF levels of neurogranin under ocrelizumab treatment, patients with and without neurogranin level increase did not differ in terms of clinical features and NEDA-3 status. Baseline neurogranin levels negatively correlated with baseline EDSS scores. Our results confirm that NFL effectively monitors treatment response of RRMS patients under ocrelizumab treatment. Neurogranin does not appear to exhibit a similar benefit in screening of RRMS disease activity. Nevertheless, lower neurogranin levels are associated with increased disability in RRMS indicating a potential disease activity biomarker function.

Search in the Periphery for Potential Inflammatory Biomarkers of Dementia with Lewy Bodies and Alzheimer's Disease.

Neuroinflammation, with altered peripheral proinflammatory cytokine production, plays a major role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), while the role of inflammation in dementia with Lewy bodies (DLB) is less known and the results of different studies are often in disagreement. The present study aimed to investigate the levels of TNFα and IL-6 in serum and supernatants, and the related DNA methylation in patients affected by DLB and AD compared to healthy controls (HCs), to clarify the role of epigenetic mechanisms of DNA promoter methylation on of pro-inflammatory cytokines overproduction. Twenty-one patients with DLB and fourteen with AD were frequency-matched for age and sex with eleven HCs. Clinical evaluation, TNFα and IL-6 gene methylation status, cytokine gene expression levels and production in serum and peripheral blood mononuclear cell (PBMC) supernatants were performed. In AD and DLB patients, higher serum levels of IL-6 and TNFα were detected than in HCs. Differences in LPS-stimulated versus spontaneous PBMCs were observed between DLB, AD, and HC in the levels of TNFα (p = 0.027) and IL-6 (p < 0.001). Higher levels were also revealed for sIL-6R in DLB (p < 0.001) and AD (p < 0.001) in comparison with HC.DNA hypomethylation in IL-6 and TNFα CpG promoter sites was detected for DLB and AD patients compared to the corresponding site in HCs. Our preliminary study documented increased levels of IL-6 and TNFα in DLB and AD patients to HCs. This overproduction can be due to epigenetic mechanisms regarding the hypomethylation of DNA promoters.

AN ISOLATED ACUTE RIGHT VENTRICULAR INFARCTION

Abstract Isolated right ventricular infarction occurs only in about 3% of the overall myocardial ischemic episodes. Clinical presentation is often insidious and variable case by case. The correct diagnosis is therefore crucial for a proper management, and a good prognosis in the short and long term. A 72–year–old patient suffering from arterial hypertension went to the emergency room of our hospital for malaise and asthenia for about 12 hours that have increased in 3–4 hours before the arrival. He was sweating, tachypneic with normal value of the oxygen saturation to the finger (SpO2:96%), with arterial hypotension (pressure values = 85/50 mmHg), turgor of the jugular veins in the absence of peripheral edema. Cardiac examination revealed no pathological noises and lung examination revealed clear lung fields. Electrocardiogram showed sinus tachycardia at a rate of 118 bpm, second degree atrioventricular (AV) block 2:1 type and an AV conduction delay with a first–degree AV block (P–Q interval: 320–330 msec). A pulmonary P wave was present and the QRS complex showed predominant R waves in V2–V3 with slight repolarization abnormalities (figure, panel A). An ST–elevation in right precordial leads, V3R and V4R was evident. (figure, panel B). Echocardiographic evaluation showed a hypertrophic left ventricle with normal volume and function, with marked enlarged right sections (figure, panels C–H). Moreover, we can observe the flattening of the interventricular septum with a D shaped left ventricle. Septal flattening occurred only in diastole, expression of RV volume overload (figure, panels F–H). After taking 180 mg of ticagrelor administrated orally and 150 mg of aspirin intravenously, the patient was immediately transferred to the catheterization laboratory for emergency coronary angiography. Coronary angiography highlighting an ostial thrombotic obstruction of a co–dominant right coronary artery (RCA) in the absence of significant stenosis of the left coronary circulation (figure, panels I–M). Primary percutaneous coronary intervention of RCA was performed with STENT implantation with a good postoperative result. (figure, panels L). During the hospital stay, the patient showed a good clinical status without any CV events, with progressively normalization of electrocardiographic abnormalities and persistent sinus rhythm. He was discharged after ten days.

Ablate and pace with conduction system pacing, Rovigo's experience

Abstract Background Several clinical data demonstrate that atrio ventricular junction (AVJ) ablation, followed by cardiac pacing, in atrial fibrillation (AF) with uncontrollable heart rate is beneficial. There are still limited data about conduction system pacing (CSP) in that setting. Aims To analyse if this “ablate and pace” strategy is feasible with good electrical results (ECG and parameters) and clinical outcomes (heart failure (HF) admission, ejection fraction (EF) and NYHA class). To analyse also differences between his bundle pacing (HBP) and left bundle branch area pacing (LBBAP) in this setting. Methods. This is an observational retrospective single center study involving 30 patients of which 11 had a HBP and 19 a LBBAP from March 2019 to June 2023 (medium follow up 33 ± 18 month). The implant procedure was performed with both stylet driven or lumenless lead. After 2 ± 2 weeks was performed the AVJ ablation. The electrical parameters were measured at the implant and every 6 – 12 months. The patients had an echocardiographic and clinical evaluation every 6 – 12 months. There was nobody with a NYHA class IV. Results The procedure was performed without complication in all patients. There were a rising in the EF (49,9 ± 14,6 vs 54,2 ± 10,4% p = 0.004). There weren’t HF admission and only 2 patients died (not for cardio–vascular causes) during follow up. There were also a decrease in NYHA class in every patient (at least one NYHA class less). 17 (57%) patients had normal ventricular conduction, only 4 (13%) had LBBB, 4 (13%) RBBB. There were not statistical difference between the QRS duration pre and after implant (129 ± 35 vs 125 ± 24 ms p = 0,06). The threshold measured at the implant were stable both in the HBP (0,75 ± 0,34 vs 1,3 ± 0,8 V @ 0,4 ms p = 0,14) and in the LBBAP (0,93 ± 0,3 vs 0,89 ± 0,3 V @ 0,4 ms p = 0,49). The LBBAP presented higher values of sensing compared with HBP (17,5 ± 7,4 vs 6,3 ± 3,3 mV p = 0,04) and less procedural (63 ± 32 vs 95 ± 41 min, p = 0,02) and fluoroscopic time (2,6 ± 2,4 vs 7,5 ± 4,1 min, p = 0,04) compared with HBP. Conclusion The CSP is feasible and safe in the setting of “ablate and pace” and results in a clear increasing in EF and clinical status of patients with good and stable ECG features and electrical parameters during follow up; the CSP indeed represent a valuable alternative to BVP in this setting. LBBAP performed better than HBP in terms of procedural and fluoroscopic time and of higher sensing values.