Objective Outcomes to Evaluate Voretigene Neparvovec Treatment Effects in Clinical Practice

Aim: To assess the efficacy of Voretigene Neparvovec (VN) treatment by objective fixation stability and chromatic pupillometry testing in clinical practice. Design: Retrospective cohort study with longitudinal follow-up. Subjects: Twelve patients (aged 7 to 34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes. Methods: Patients treated at the same center with VN were evaluated over a 12-month post-treatment follow-up by subjective and objective tests. Furthermore, patients treated with VN who developed atrophy were compared to those who did not. Main outcome measures: Best corrected visual acuity (BCVA), full field stimulus threshold test (FST), semi-automated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over a 12-month follow-up RESULTS: Significant improvements of BCVA (p<0.001), SKVF (p<0.05) and FST (p<0.001) were already observed 45 days after treatment and were maintained at the 12-month timepoint. Fixation stability, assessed by microperimetry, improved significantly (p<0.05) after treatment. Chromatic pupillometry showed significant improvements (p<0.05) at the 6- and 12-month timepoints. The increase in maximum pupillary constriction significantly (p<0.001) correlated with higher retinal sensitivity in FST. Four patients developed multifocal retinal atrophy in both eyes, detected at the 6-month timepoint, but this atrophy was not generally associated with worse visual function outcomes. Conclusions: This study is the first attempt to demonstrate the efficacy of VN treatment in real life using objective tests in addition to those normally performed in clinical practice. Our findings show a significant improvement of retinal function both in subjective assessments, such as BCVA, SKVF and FST, and in objective measurements of fixation stability and maximum pupillary constriction. Moreover, the significant correlation between maximum pupillary constriction and light sensitivity thresholds corroborates the introduction of chromatic pupillometry as an objective test to better assess treatment outcomes in patients with inherited retinal dystrophies

Optimising surgical anastomosis in ileocolic resection for Crohn’s disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES)

Background: The most common intestinal operation in Crohn's disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption. Methods: This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs. Discussion: The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines. Trial registration: NCT05246917 for HAND2END and NCT05578235 for End2End ( http://www. Clinicaltrials: gov/ )

Parecoxib decreases cellular growth and Bcl‐2 protein levels in primary cultures of keloid fibroblasts

: Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 μM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 μM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids

The Lipid-Lowering Efficacy of a Nutraceutical Combination Including Leucoselect Phytosome, Red Yeast Rice, Policosanol and Folic Acid in Dyslipidaemia Patients: Real-World Insights

Abstract: Background: Cardiovascular disease is a global health concern and reducing plasma LDL-Clevels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of anutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folicacid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. Materials and Methods:We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular riskwho were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses,encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline priorto initiating treatment and repeated at the 12-week mark following administration of the studynutraceutical. Results: Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) wereincluded. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%)and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable overthe time. The adherence to therapy was 99% and the persistence was maximum. Conclusions: Thenutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folicacid significantly reduced the LDL-c plasma levels, consistent with previous research showing thatthe bioactive component in red yeast rice—lovastatin—is effective in addressing problems with lipidmetabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in areal-world setting. (9) (PDF) The Lipid-Lowering Efficacy of a Nutraceutical Combination Including Leucoselect Phytosome, Red Yeast Rice, Policosanol and Folic Acid in Dyslipidaemia Patients: Real-World Insights. Available from: https://www.researchgate.net/publication/379455055_The_Lipid-Lowering_Efficacy_of_a_Nutraceutical_Combination_Including_Leucoselect_Phytosome_Red_Yeast_Rice_Policosanol_and_Folic_Acid_in_Dyslipidaemia_Patients_Real-World_Insights [accessed Apr 04 2024]

L’occupazione dei luoghi di altura in epoca sannitica: novità dal territorio tra Limatola e Castel Morrone (Campania)

The occupation of the hills in Samnite period: news from the territory between Limatola and Castel Morrone (Campania-Italy) · The ongoing research conducted at the borders between Limatola (Benevento district) and Castel Morrone (Caserta district) has facilitated the identification of a small, fortified site on the peak of Monte Montagnano situated in an area overlooking the Volturno River. This paper presents an analysis of structural features, along with an interpretative and chronological proposal based on the study of aerial and satellite photographs and survey findings. The relationship between this site and other Samnite hillforts in the middle Volturno Valley will also be analysed.Le ricerche in corso nella fascia territoriale ai confini tra i comuni di Limatola (bn) e Castel Morrone (ce) hanno consentito di individuare un piccolo sito fortificato in corrispondenza di Monte Montagnano, in un’area prospiciente il corso del fiume Volturno. Sulla base di quanto rilevato sulla documentazione aerofotografica esaminata e sul terreno si presentano un’analisi delle caratteristiche struttive del sito, una proposta interpretativa e cronologica nell’ambito delle modalità di popolamento di epoca sannitica e di interrelazione del piccolo centro con gli altri siti fortificati della media valle del Volturno

Sphingolipidomic profiling of human Dental Pulp Stem Cells undergoing osteogenic differentiation

It is now recognized that sphingolipids are involved in the regulation and pathophysiology of several cellular processes such as proliferation, migration, and survival. Growing evidence also implicates them in regulating the behaviour of stem cells, the use of which is increasingly finding application in regenerative medicine. A shotgun lipidomic study was undertaken to determine whether sphingolipid biomarkers exist that can regulate the proliferation and osteogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). Sphingolipids were extracted and identified by direct infusion into an electrospray mass spectrometer. By using cells cultured in osteogenic medium and in medium free of osteogenic stimuli, as a control, we analyzed and compared the SPLs profiles. Both cellular systems were treated at different times (72 hours, 7 days, and 14 days) to highlight any changes in the sphingolipidomic profiles in the subsequent phases of the differentiation process. Signals from sphingolipid species demonstrating clear differences were selected, their relative abundance was determined, and statistical differences were analyzed. Thus, our work suggests a connection between sphingolipid metabolism and hDPSC osteogenic differentiation and provides new biomarkers for improving hDPSC-based orthopaedic regenerative medicine