Lu-PRRT Used More Intensively on Advanced Gastro-Entero-Pancreatic and Lung Neuroendocrine Neoplasms: Preliminary Results on Toxicity from a Randomized Study.

Introduction: Lu-PRRT in neuroendocrine tumors is usually delivered with a total cumulative activity (TCA) of 29.6 GBq, divided into 4 cycles and with fixed interval between cycles (IBCs) of 8 weeks. Based on previous radiobiological studies, reducing IBC could improve efficacy without increasing toxicity.

Peptide Receptor Radionuclide Therapy in Advanced Refractory Meningiomas: Efficacy and Toxicity in a Long Follow-up.

Recurrence of meningiomas after surgery and radiotherapy deserves specific attention because of the lack of active third-line therapies. Somatostatin receptors are usually overexpressed on the cell membrane of meningiomas, and this has led the way to a radionuclide theranostic approach. Diagnoses with Ga-DOTA-octreotide and peptide receptor radionuclide therapy (PRRT) with Y/Lu-DOTA-octreotide are currently possible options within experimental protocols or as compassionate use in small patient groups.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

Purpose: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.

Methods: Fifty-three patients (mean age, 33.6 ± 16.

Objective Outcomes to Evaluate Voretigene Neparvovec Treatment Effects in Clinical Practice.

Purpose: 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 7-34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes.

An Italian case series' description of thiamine responsive megaloblastic anemia syndrome: importance of early diagnosis and treatment.

Background: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations.

Pars Plana Vitrectomy in Inherited Retinal Diseases: A Comprehensive Review of the Literature.

Inherited retinal diseases (IRDs) are a group of clinically and genetically heterogeneous disorders that may be complicated by several vitreoretinal conditions requiring a surgical approach. Pars plana vitrectomy (PPV) stands as a valuable treatment option in these cases, but its application in eyes with such severely impaired chorioretinal architectures remains controversial. Furthermore, the spreading of gene therapy and the increasing use of retinal prostheses will end up in a marked increase in demand for PPV surgery for IRD patients.

Clinical Applications of Optical Coherence Tomography Angiography in Inherited Retinal Diseases: An Up-to-Date Review of the Literature.

Optical coherence tomography angiography (OCT-A) is a valuable imaging technique, allowing non-invasive, depth-resolved, motion-contrast, high-resolution images of both retinal and choroidal vascular networks. The imaging capabilities of OCT-A have enhanced our understanding of the retinal and choroidal alterations that occur in inherited retinal diseases (IRDs), a group of clinically and genetically heterogeneous disorders that may be complicated by several vascular conditions requiring a prompt diagnosis. In this review, we aimed to comprehensively summarize all clinical applications of OCT-A in the diagnosis and management of IRDs, highlighting significant vascular findings on retinitis pigmentosa, Stargardt disease, choroideremia, Best disease and other less common forms of retinal dystrophies.

Genetic epidemiology of inherited retinal diseases in a large patient cohort followed at a single center in Italy.

Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular diagnosis for 2036 patients (from 1683 unrelated families).

Navigated 577-nm subthreshold micropulse retinal laser treatment for peripapillary pachychoroid syndrome.

Purpose: To report a case of peripapillary pachychoroid syndrome (PPS) successfully treated with navigated subthreshold micropulse laser (SML).

Observations: A 65-year-old male was referred to our retina service complaining a worsening vision in the left eye (LE) over the past 6 months. A complete ophthalmological evaluation including best corrected visual acuity (BCVA) measurement, spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) was performed.

Metabolomic fingerprinting of renal disease progression in Bardet-Biedl syndrome reveals mitochondrial dysfunction in kidney tubular cells.

Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis. studies were conducted in two kidney-derived epithelial cell lines, where was stably deleted (IMCD3--/-cells) and over-expressed.

Visual function and retinal changes after voretigene neparvovec treatment in children with biallelic RPE65-related inherited retinal dystrophy.

To report quantitative retinal changes assessed by spectral-domain optical coherence tomography (SD-OCT) in children treated with voretigene neparvovec (VN) at a single center in Italy. Retrospective review of six consecutive pediatric patients with biallelic RPE65-related dystrophy treated bilaterally with VN. SD-OCT scans were analyzed to extract Early Treatment Diabetic Retinopathy Study (ETDRS) thickness maps of the whole retina and the outer nuclear layer (ONL).

Narrative medicine to investigate the quality of life and emotional impact of inherited retinal disorders through the perspectives of patients, caregivers and clinicians: an Italian multicentre project.

Objectives: Although inherited retinal disorders (IRDs) related to the gene encoding the retinal pigment epithelium 65kD protein (RPE65) significantly impact the vision-related quality of life (VRQoL), their emotional and social aspects remain poorly investigated in Italy. Narrative Medicine (NM) reveals the more intimate aspects of the illness experience, providing insights into clinical practice.

Design And Setting: This NM project was conducted in Italy between July and December 2020 and involved five eye clinics specialised in IRDs.

Anatomical and Functional Effects of Oral Administration of Curcuma Longa and Boswellia Serrata Combination in Patients with Treatment-Naïve Diabetic Macular Edema.

Anti-vascular endothelial growth factor nowdays represents the standard of care for diabetic macular edema (DME). Nevertheless, the burden of injections worldwide has created tremendous stress on the healthcare system during the COVID-19 pandemic. The aim of this study was to investigate the effects of the oral administration of Curcuma longa and Boswellia serrata (Retimix®) in patients with non-proliferative diabetic retinopathy (DR) and treatment-naïve DME < 400 μm, managed during the COVID-19 pandemic.

Production and Quality Control of [Lu]Lu-PSMA-I&T: Development of an Investigational Medicinal Product Dossier for Clinical Trials.

Since prostate cancer is the most commonly diagnosed malignancy in men, the theranostic approach has become very attractive since the discovery of urea-based PSMA inhibitors. Different molecules have been synthesized starting from the Glu-urea-Lys scaffold as the pharmacophore and then optimizing the linker and the chelate to improve functional characteristics. This article aimed to highlight the quality aspects, which could have an impact on clinical practice, describing the development of an Investigational Medicinal Product Dossier (IMPD) for clinical trials with [177Lu]Lu-PSMA-I&T in prostate cancer and other solid tumors expressing PSMA.

Laminin N-terminus α31 expression during development is lethal and causes widespread tissue-specific defects in a transgenic mouse model.

Laminins (LMs) are essential components of all basement membranes where they regulate an extensive array of tissue functions. Alternative splicing from the laminin α3 gene produces a non-laminin but netrin-like protein, Laminin N terminus α31 (LaNt α31). LaNt α31 is widely expressed in intact tissue and is upregulated in epithelial cancers and during wound healing.

The role of clinical trials in the sustainability of the Italian national health service cancer drug expenditure.

Objective: Clinical trials offer new and potentially more effective therapeutic options for cancer patients and a potential cost-saving opportunity, especially considering that trial drugs are provided free-of-charge. The aim of this study was to analyse drug-related cost savings in clinical trials in a cancer institute over a 3 year period. The cost savings relate to the pharmaceutical expenditure of our centre, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori".

Applications of Optical Coherence Tomography in the Ocular Diagnosis: From the Tear Film to the Sclera.

The latest technological developments have radically impacted the daily practice of ophthalmologists, thanks to the advent of novel diagnostic tools that facilitate an early diagnosis and allow a better management of ocular disorders [...

ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study.

Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval.

Theragnostic in neuroendocrine tumors.

In the last few decades, the incidence and prevalence of neuroendocrine tumors has been increasing. The theragnostic approach, that allows the diagnosis and treatment of different neoplasms with the same ligand, is a typical nuclear medicine tool. Applied for years, is also pivotal in neuroendocrine tumors (NETs) where it has improved the diagnostic accuracy and the therapeutic efficacy with impact on patient's survival.

Care Pathway of RPE65-Related Inherited Retinal Disorders from Early Symptoms to Genetic Counseling: A Multicenter Narrative Medicine Project in Italy.

Purpose: Timely detection and multidisciplinary management of -related inherited retinal disorders (IRDs) can significantly improve both disease management and patient care. Thus, this Narrative Medicine (NM) project aimed to investigate the evolution of the care pathway and the expectations on genetic counseling and gene therapy by patients, caregivers, and healthcare professionals.

Patients And Methods: This project was conducted between July and December 2020, involving five Italian eye clinics specialized in IRDs, targeted pediatric and adult patients, their caregivers, attending retinologists and multidisciplinary healthcare professionals.

Voretigene Neparvovec Gene Therapy in Clinical Practice: Treatment of the First Two Italian Pediatric Patients.

Purpose: To present visual outcomes of the first two Italian patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec (VN).

Methods: Two pediatric patients with RPE65-IRD were treated with VN in both eyes. Patients were evaluated by best-corrected visual acuity (BCVA), full-field stimulus threshold (FST) test, semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over 6 months.

Molecular Characterization of Choroideremia-Associated Deletions Reveals an Unexpected Regulation of Gene Transcription.

Choroideremia (CHM) is a X-linked recessive chorioretinal dystrophy due to deficiency of the gene product, i.e., Rab escort protein isoform 1 (REP1).

Circulating androgen receptor gene amplification and resistance to Lu-PSMA-617 in metastatic castration-resistant prostate cancer: results of a Phase 2 trial.

Background: In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [Lu]-PSMA-617 activity and the clinical utility of levels of plasma androgen receptor (AR) gene in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC).

Methods: We determined AR copy number in pretreatment plasma samples. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CIs) in order to evaluate the independent relevance of AR status and to evaluate patients with early progressive disease (PD) defined as treatment interruption occurring within 4 months after the start of Lu-PSMA-617.