355 results on '"L. De Rosa"'
Search Results
152. [Disease caused by homozygosis of elevated Hb A-2. 1st description]
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N, QUATTRIN, L, DE ROSA, E, DINI, and V, VENTRUTO
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Hemoglobins ,Hemoglobins, Abnormal ,beta-Thalassemia ,Humans ,Anemia ,Anemia, Sickle Cell - Published
- 1962
153. [On the behavior of different types of hemoglobin (Hb A, A2, F, S and 'Bart's') in thalassemia, drepanocytosis and microdrepanocythemia]
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V, VENTRUTO, L, DE ROSA, R, CIMINO, and N, QUATTRIN
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Anemia, Hypochromic ,Hemoglobins ,Hemoglobins, Abnormal ,beta-Thalassemia ,Humans ,Thalassemia ,Anemia, Sickle Cell ,Sickle Cell Trait - Published
- 1962
154. Autologous blood stem cell collection after chemotherapy in patients with sensitive and refractory malignancies: A multicenter retrospective study
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Indovina A, P. Benedetti Panici, Ignazio Majolino, Quaglietta Am, L De Rosa, G. Fioritoni, Giacomo Menichella, Rosanna Scimè, Giuseppe Leone, A. De Laurenzi, A. Nicolucci, Luca Pierelli, Antonio Iacone, and A. Montuoro
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Retrospective cohort study ,General Medicine ,medicine.disease ,Lymphoma ,Biomaterials ,Leukemia ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Stem cell ,Ovarian cancer ,business ,Multiple myeloma - Abstract
A retrospective study was undertaken to assess the factors affecting the yield of peripheral blood stem cell (PBSC) collections after chemotherapy. Fifty-five patients with malignancies, observed in 4 Italian Institutions from January 1987 to June 1991 were eligible for evaluation. This series included 19 non-Hodgkin lymphoma, 11 multiple myeloma, 9 ovarian cancer, 7 Hodgkin disease, 7 acute non-lymphocytic leukemia, 1 acute lymphoblastic leukemia, 1 neuroblastoma. Five hundred and twenty two PBSC collections were performed on 55 patients after a median of 18 days after the start of chemotherapy. The yields of PBSC collections were related to the dose of cytoreductive chemotherapy exploited for PBSC mobilization and to the number of circulating white blood cells, colony forming unit granulocyte/macrophage (CFU-GM) and the percentage of monocytes at the time of collection. Forty-eight patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant related complications.
155. Monitoring degradation of single and multilayer organic coatings. I. Absorption and transport of water: Theoretical analysis and methods
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D. B. Mitton, Francesco Bellucci, L. De Rosa, Tullio Monetta, L. D., Rosa, Monetta, Tullio, D. b., Mitton, and Bellucci, Francesco
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Absorption of water ,Renewable Energy, Sustainability and the Environment ,Chemistry ,Organic coatings ,Analytical chemistry ,Humidity ,engineering.material ,Condensed Matter Physics ,Capacitance ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Absorption, Capacitance, Capacitance measurement, Degradation, Gravimetric analysis, Mathematical models, Multilayers, Numerical analysis, Phase equilibria, Transport properties, Water ,Coating ,Materials Chemistry ,Electrochemistry ,engineering ,Gravimetric analysis ,Degradation (geology) ,Equilibrium water uptake, Water transport ,Absorption (electromagnetic radiation) ,Water content - Abstract
This paper presents a mathematical model describing the change in the capacitance of both single and multilayer organic coatings exposed to a wet environment. The indication is that the capacitance technique can successfully be employed to monitor, in situ, the absorption of water through single-layer organic coatings for values of equilibrium water uptake to a maximum of 5% by volume. In addition, this model indicates a relationship for d(ln C)/d{radical}t, where C is the coating capacitance and t is the time of exposure to the environment, that can be used to rank different single-layer coatings. Conversely, no quantitative correlation between mass uptake and coating capacitance was found for a multilayer coating system, even for low values of water uptake. Although, at face value, these findings suggest that this technique may be inappropriate for in situ monitoring of water absorption in such complex systems, a comparison between gravimetric and capacitance data indicates that useful qualitative information may still be generated by the use of the latter technique.
156. Index autorum ad Vol. 37
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M. Landy, G. Salen, A. Tsoukantas, H.O. Klein, B. Angelopoulos, L. De Rosa, Tadashi Maekawa, Gisela Haemmerxi, H. Ebara, S. Özsoylu, Cimino R, K. Nakao, A. Eleftheriadou, B. Lagerlöf, H. Peters, B. Gullbring, Takuo Shirakura, H. Horiuchi, D. Karalis, A. Heller, P. Bianghi, Quattrin N, V. Ventruto, H.R. Schumacher, and Dini E
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Index (economics) ,Statistics ,Hematology ,General Medicine ,Mathematics - Published
- 1967
157. I cambi esteri del Regno di Napoli dal 1591 al 1707, in Biblioteca del Bollettino dell'Archivio del Banco di Napoli
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L. de Rosa and E. Perini
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Economics and Econometrics ,History ,Political science - Published
- 1960
158. Magnetic Nulls and Super-radial Expansion in the Solar Corona.
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Sarah E. Gibson, Kevin Dalmasse, Laurel A. Rachmeler, Marc L. De Rosa, Steven Tomczyk, Giuliana de Toma, Joan Burkepile, and Michael Galloy
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- 2017
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159. DERIVING THE PROPERTIES OF CORONAL PRESSURE FRONTS IN 3D: APPLICATION TO THE 2012 MAY 17 GROUND LEVEL ENHANCEMENT.
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A. P. Rouillard, I. Plotnikov, R. F. Pinto, M. Tirole, M. Lavarra, P. Zucca, R. Vainio, A. J. Tylka, A. Vourlidas, M. L. De Rosa, J. Linker, A. Warmuth, G. Mann, C. M. S. Cohen, and R. A. Mewaldt
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SOLAR loop prominences ,SOLAR energetic particles ,SOLAR activity ,CORONAL mass ejections ,HELIOSPHERE - Abstract
We study the link between an expanding coronal shock and the energetic particles measured near Earth during the ground level enhancement of 2012 May 17. We developed a new technique based on multipoint imaging to triangulate the three-dimensional (3D) expansion of the shock forming in the corona. It uses images from three vantage points by mapping the outermost extent of the coronal region perturbed by the pressure front. We derive for the first time the 3D velocity vector and the distribution of Mach numbers, M
FM , of the entire front as a function of time. Our approach uses magnetic field reconstructions of the coronal field, full magnetohydrodynamic simulations and imaging inversion techniques. We find that the highest MFM values appear near the coronal neutral line within a few minutes of the coronal mass ejection onset; this neutral line is usually associated with the source of the heliospheric current and plasma sheet. We illustrate the variability of the shock speed, shock geometry, and Mach number along different modeled magnetic field lines. Despite the level of uncertainty in deriving the shock Mach numbers, all employed reconstruction techniques show that the release time of GeV particles occurs when the coronal shock becomes super-critical (MFM > 3). Combining in situ measurements with heliospheric imagery, we also demonstrate that magnetic connectivity between the accelerator (the coronal shock of 2012 May 17) and the near-Earth environment is established via a magnetic cloud that erupted from the same active region roughly five days earlier. [ABSTRACT FROM AUTHOR]- Published
- 2016
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160. Interaction between fac-[Re(H2O)3(CO)3]+ ion and Histidine in aqueous solutions
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DE TOMMASO, GAETANO, Iuliano, M., De Rosa, L., Malgieri, G., Fattorusso, R., Romanelli, A., D’Andrea, L. D., Isernia, C., G. De Tommaso, M. Iuliano, L. De Rosa, G. Malgieri, R. Fattorusso, A. Romanelli, L. D. D’Andrea, C. Isernia, DE TOMMASO, Gaetano, Iuliano, M., De Rosa, L., Malgieri, G., Fattorusso, R., Romanelli, A., D’Andrea, L. D., and Isernia, C.
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- 2016
161. p63 control of desmosome gene expression and adhesion is compromised in AEC syndrome
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Maria Rosaria Mollo, Spiro Getsios, Raffaele Ambrosio, Caterina Missero, Huiqing Zhou, Helen A. Thomason, Giustina Ferone, Domenico Salvatore, Jill Dixon, Laura De Rosa, Hans van Bokhoven, Dario Antonini, G., Ferone, M. R., Mollo, H. A., Thomason, Antonini, Dario, H., Zhou, R., Ambrosio, L., De Rosa, Salvatore, Domenico, S., Getsio, H., van Bokhoven, J., Dixon, and Missero, Caterina
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Keratinocytes ,Genetics and epigenetic pathways of disease [NCMLS 6] ,Epithelium ,Mice ,Ectodermal Dysplasia ,Desmosome ,Eye Abnormalities ,Cloning, Molecular ,Luciferases ,Cells, Cultured ,Genetics (clinical) ,Skin ,Mice, Knockout ,Regulation of gene expression ,integumentary system ,biology ,Articles ,Desmosomes ,General Medicine ,Cell biology ,Cleft Palate ,ErbB Receptors ,medicine.anatomical_structure ,Desmoglein 1 ,Female ,Desmocollin ,Keratinocyte ,Chromatin Immunoprecipitation ,Hay–Wells syndrome ,Cleft Lip ,Real-Time Polymerase Chain Reaction ,Cell Adhesion ,Genetics ,medicine ,Animals ,Humans ,Desmosomal Cadherins ,Molecular Biology ,Desmoplakin ,Eyelids ,Membrane Proteins ,medicine.disease ,Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory [NCMLS 6] ,Mice, Inbred C57BL ,stomatognathic diseases ,Gene Expression Regulation ,Mutation ,Immunology ,biology.protein ,Epidermis - Abstract
Contains fulltext : 118008.pdf (Publisher’s version ) (Open Access) Ankyloblepharon, ectodermal defects, cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the p63 gene, essential for embryonic development of stratified epithelia. The most severe cutaneous manifestation of this disorder is the long-lasting skin fragility associated with severe skin erosions after birth. Using a knock-in mouse model for AEC syndrome, we found that skin fragility was associated with microscopic blistering between the basal and suprabasal compartments of the epidermis and reduced desmosomal contacts. Expression of desmosomal cadherins and desmoplakin was strongly reduced in AEC mutant keratinocytes and in newborn epidermis. A similar impairment in desmosome gene expression was observed in human keratinocytes isolated from AEC patients, in p63-depleted keratinocytes and in p63 null embryonic skin, indicating that p63 mutations causative of AEC syndrome have a dominant-negative effect on the wild-type p63 protein. Among the desmosomal components, desmocollin 3, desmoplakin and desmoglein 1 were the most significantly reduced by mutant p63 both at the RNA and protein levels. Chromatin immunoprecipitation experiments and transactivation assays revealed that p63 controls these genes at the transcriptional level. Consistent with reduced desmosome function, AEC mutant and p63-deficient keratinocytes had an impaired ability to withstand mechanical stress, which was alleviated by epidermal growth factor receptor inhibitors known to stabilize desmosomes. Our study reveals that p63 is a crucial regulator of a subset of desmosomal genes and that this function is impaired in AEC syndrome. Reduced mechanical strength resulting from p63 mutations can be alleviated pharmacologically by increasing desmosome adhesion with possible therapeutic implications.
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- 2012
162. p63 Suppresses Non-epidermal Lineage Markers in a Bone Morphogenetic Protein-dependent Manner via Repression of Smad7
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Giustina Ferone, Laura De Rosa, Paul B. Yu, Rong Han, Monia Teresa Russo, Caterina Missero, Dario Antonini, L., De Rosa, Antonini, Dario, G., Ferone, M. T., Russo, P. B., Yu, R., Han, and Missero, Caterina
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Keratinocytes ,animal structures ,Bone Morphogenetic Protein 7 ,SMAD ,Biology ,Bone morphogenetic protein ,Biochemistry ,Bone morphogenetic protein 2 ,Smad7 Protein ,Mice ,Molecular Basis of Cell and Developmental Biology ,Animals ,Cell Lineage ,Molecular Biology ,Cells, Cultured ,integumentary system ,Bone morphogenetic protein 10 ,Cell Biology ,Phosphoproteins ,Molecular biology ,Cell biology ,BMPR2 ,Bone morphogenetic protein 7 ,Bone morphogenetic protein 6 ,Bone morphogenetic protein 5 ,Epidermal Cells ,Gene Expression Regulation ,Bone Morphogenetic Proteins ,embryonic structures ,Trans-Activators ,Biomarkers ,Signal Transduction - Abstract
p63, a p53 family member, plays an essential role in epidermal development by regulating its transcriptional program. Here we report a previously uncovered role of p63 in controlling bone morphogenetic protein (BMP) signaling, which is required for maintaining low expression levels of several non-epidermal genes. p63 represses transcription of the inhibitory Smad7 and activates Bmp7, thereby sustaining BMP signaling. In the absence of p63, compromised BMP signaling leads to inappropriate non-epidermal gene expression in postnatal mouse keratinocytes and in embryonic epidermis. Reactivation of BMP signaling by Smad7 knockdown and/or, to a lesser extent, by BMP treatment suppresses expression of non-epidermal genes in the absence of p63. Canonical BMP/Smad signaling is essential for control of non-epidermal genes as use of a specific inhibitor, or simultaneous knockdown of Smad1 and Smad5 counteract suppression of non-epidermal genes. Our data indicate that p63 prevents ectopic expression of non-epidermal genes by a mechanism involving Smad7 repression and, to a lesser extent, Bmp7 induction, with consequent enhancement of BMP/Smad signaling.
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- 2009
163. Skin fragility is associated with reduced desmosome formation in AEC syndrome
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Ferone, G., Thomason, H. A., Rosa, L., Zhou, H., J.H.L.M. (Hans) van Bokhoven, Dixon, J., Missero, C., G., Ferone, H. A., Thomason, L., De Rosa, H., Zhou, H., van Bokhoven, J., Dixon, and Missero, Caterina
- Published
- 2012
164. Prefazione al libro Lingua Madre e Lingua Matrigna. Riflessioni su diglossia, bilinguismo sociale e literacy
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DE LAURENTIIS, Antonella, A. De Laurentiis e G. L. De Rosa, and DE LAURENTIIS, Antonella
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bilinguismo ,politiche linguistiche ,diglossia - Published
- 2011
165. Lingua pura e lingua panispanica: l'eterno ritorno di una polemica
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DE LAURENTIIS, Antonella, A. De Laurentiis e G. L. De Rosa, and DE LAURENTIIS, Antonella
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lingua ,identità ,politiche linguistiche - Published
- 2011
166. Degradation of zinc oxide thin films in aqueous environment: Part I - Bare Films
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Rosa, L., Perugini, N., Mitton, D. B., Tullio MONETTA, Bellucci, F., Springer, J., L., De Rosa, N., Perugini, D. B., Mitton, Monetta, Tullio, Bellucci, Francesco, and J., Springer
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Mechanics of Materials ,Mechanical Engineering ,Materials Chemistry ,Metals and Alloys ,Environmental Chemistry ,General Medicine ,Surfaces, Coatings and Films - Published
- 2001
167. Orthoplastic Management of Lower Limb Traumas: A Retrospective Study on Polytraumas Versus Isolated Injuries.
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Gatto A, Stucchi S, Brambilla L, Cavalli E, Giacomini G, De Rosa L, Leone G, Belingheri M, Ribuffo D, Zatti G, and Marchesi A
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- Humans, Retrospective Studies, Male, Female, Adult, Middle Aged, Fracture Fixation, Internal methods, Soft Tissue Injuries surgery, Soft Tissue Injuries therapy, Injury Severity Score, Leg Injuries therapy, Leg Injuries surgery, Treatment Outcome, Multiple Trauma therapy, Multiple Trauma surgery, Plastic Surgery Procedures methods, Fractures, Open surgery, Fractures, Open economics
- Abstract
Background: Open fractures of the lower limb represent a common challenge for trauma centers. Even where national guidelines are available, these standards are frequently missing. Our study evaluates the influence of polytrauma on the adherence to the timing and management required in an orthoplastic approach., Patients and Methods: A retrospective review was performed on 36 patients affected by a Gustilo-Anderson grade IIIA, IIIB, or IIIC fracture of the lower limb between 2018 and 2022. Data related to patient management were analyzed: time to the first evaluation by a plastic surgeon, time to soft tissue coverage, time to definitive osteosynthesis, days in intensive care unit (ICU), days of hospitalization, and total cost of hospital stay. Patient satisfaction was evaluated through the administration of 2 questionnaires: the Enneking and the Foot Function Index (FFI)., Results: In 23 patients (63.9%), a soft tissue reconstruction was required. Of these, 13 were polytraumas (PT) (56.5%) and 10 were affected by an isolated lower limb fracture (ILLF) (43.5%). The median time to wound excision was 7.0 days (IQR, 0-16.0) in the PT group and 12.5 days (IQR, 1-41.0) in the ILLF group, whereas the mean time to soft tissue coverage was 15.0 days (IQR, 4.0-17.0) in the PT group and 38.0 days (IQR, 25.0-65.0) in the ILLF group. Mean time to definitive fixation was 33.0 days (IQR, 6.5-70.0) in the PT group and 16.5 days (IQR, 3.0-26.0) in the ILLF group. Statistically significant difference was reported on mean time to soft tissue coverage, whereas not relevant differences were reported on mean time to plastic surgeon involvement, first debridement, definitive fixation, days of hospitalization, costs, and Enneking and FFI score., Conclusion: This is the first study comparing the effectiveness of the orthoplastic approach between isolated lower limb fractures and polytraumas. According to our study, open lower limb fracture management is paradoxically more effective in polytraumas rather than in isolated injuries because a multidisciplinary approach is mandatory in severely injured and compromised patients., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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168. Robotic Assisted Transcranial Doppler Monitoring in Acute Neurovascular Care: A Feasibility and Safety Study.
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Fattorello Salimbeni A, Kulyk C, Favruzzo F, De Rosa L, Viaro F, Pieroni A, Mozzetta S, Vosko MR, and Baracchini C
- Abstract
Background: Transcranial color Doppler (TCD) is currently the only noninvasive bedside tool capable of providing real-time information on cerebral hemodynamics. However, being operator dependent, TCD monitoring is not feasible in many institutions. Robotic assisted TCD (ra-TCD) was recently developed to overcome these constraints. The aim of this study was to evaluate the safety and feasibility of cerebral monitoring with a novel ra-TCD in acute neurovascular care., Methods: This is a two-center prospective study conducted between August 2021 and February 2022 at Padua University Hospital (Padua, Italy) and Kepler University Hospital (Linz, Austria). Adult patients with conditions impacting cerebral hemodynamics or patients undergoing invasive procedures affecting cerebral hemodynamics were recruited for prolonged monitoring (> 30 min) of the middle cerebral artery with a novel ra-TCD (NovaGuide Intelligent Ultrasound, NeuraSignal, Los Angeles, CA). Manual TCD was also performed for comparison by an experienced operator. Feasibility and safety rates were recorded., Results: A total of 92 patients (age: mean 68.5 years, range 36-91; sex: male 57 [62%]) were enrolled in the two centers: 54 in Padua, 38 in Linz. The examination was feasible in the majority of patients (85.9%); the head cradle design and its radiopacity hindered its use during carotid endarterectomy and mechanical thrombectomy. Regarding safety, only one patient (1.1%) reported a minor local edema due to prolonged probe pressure. Velocity values were similar between ra-TCD and manual TCD., Conclusions: This novel ra-TCD showed an excellent safety and feasibility and proved to be as reliable as manual TCD in detecting blood flow velocities. These findings support its wider use for cerebral hemodynamics monitoring in acute neurovascular care. However, further technical improvements are needed to expand the range of applicable settings., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)
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- 2024
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169. Prospective randomized clinical trial evaluating efficacy and safety of a new ophthalmic viscosurgical device in patients undergoing cataract surgery.
- Author
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De Rosa L, Furiosi L, Pellegrini M, Yu AC, Scorcia V, and Busin M
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- Humans, Prospective Studies, Male, Female, Aged, Chondroitin Sulfates, Middle Aged, Treatment Outcome, Endothelium, Corneal pathology, Drug Combinations, Aged, 80 and over, Visual Acuity physiology, Intraocular Pressure physiology, Hyaluronic Acid therapeutic use, Phacoemulsification, Lens Implantation, Intraocular, Viscosupplements administration & dosage
- Abstract
Purpose: To evaluate the efficacy and safety of Bio-Hyalur LVD compared with Viscoat ophthalmic viscosurgical device (OVD) in patients undergoing routine cataract surgery., Setting: 2 tertiary eyecare hospitals in Italy., Design: Prospective randomized clinical trial., Methods: This study compared the outcomes of Bio-Hyalur LVD vs Viscoat OVD in patients undergoing standard cataract surgery with phacoemulsification and intraocular lens implantation from January 2021 to April 2022. The primary outcome was mean change in IOP at 6 hours. Secondary outcomes included 1-day, 7-day, 30-day, and 90-day mean intraocular pressure (IOP); 7-day, 30-day, and 90-day corrected distance visual acuity; endothelial cell density (ECD); change in central corneal thickness (CCT); and complications including intraocular inflammation., Results: 84 eyes of 84 patients (n = 41 in the Bio-Hyalur LVD group and n = 43 in the Viscoat group) were screened, enrolled, randomized, and included in the analysis. Mean change in IOP was significantly higher in the Viscoat group than in the Bio-Hyalur LVD group 6 hours ( P = .034), 7 days ( P < .001), 30 days ( P < .001), and 90 days ( P = .003) postoperatively. Mean change in uncorrected distance visual acuity and corrected distance visual acuity was significantly higher in the Bio-Hyalur LVD group 30 and 90 days postoperatively. No significant differences in ECD, CCT, and complication rates were observed between groups at any timepoint., Conclusions: Bio-Hyalur LVD OVD was safe and effective in patients undergoing routine cataract surgery. Bio-Hyalur LVD OVD did not confer a higher risk of postoperative increase in IOP., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)
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- 2024
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170. Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family.
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Trinchillo A, Valente V, Esposito M, Migliaccio M, Iovino A, Picciocchi M, Cuomo N, Caccavale C, Nocerino C, De Rosa L, Salvatore E, Pierantoni GM, Menchise V, Paladino S, and Criscuolo C
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- Humans, Female, Male, Adult, Middle Aged, Phenotype, Young Adult, Adolescent, Genes, Dominant, Child, Aged, Spastic Paraplegia, Hereditary genetics, Pedigree, Membrane Proteins genetics, Mutation
- Abstract
Background: SPG18 is caused by mutations in the endoplasmic reticulum lipid raft associated 2 (ERLIN2) gene. Autosomal recessive (AR) mutations are usually associated with complicated hereditary spastic paraplegia (HSP), while autosomal dominant (AD) mutations use to cause pure SPG18., Aim: To define the variegate clinical spectrum of the SPG18 and to evaluate a dominant negative effect of erlin2 (encoded by ERLIN2) on oligomerization as causing differences between AR and AD phenotypes., Methods: In a four-generation pedigree with an AD pattern, a spastic paraplegia multigene panel test was performed. Oligomerization of erlin2 was analyzed with velocity gradient assay in fibroblasts of the proband and healthy subjects., Results: Despite the common p.V168M mutation identified in ERLIN2, a phenoconversion to amyotrophic lateral sclerosis (ALS) was observed in the second generation, pure HSP in the third generation, and a complicated form with psychomotor delay and epilepsy in the fourth generation. Erlin2 oligomerization was found to be normal., Discussion: We report the first AD SPG18 family with a complicated phenotype, and we ruled out a dominant negative effect of V168M on erlin2 oligomerization. Therefore, our data do not support the hypothesis of a relationship between the mode of inheritance and the phenotype, but confirm the multifaceted nature of SPG18 on both genetic and clinical point of view. Clinicians should be aware of the importance of conducting an in-depth clinical evaluation to unmask all the possible manifestations associated to an only apparently pure SPG18 phenotype. We confirm the genotype-phenotype correlation between V168M and ALS emphasizing the value of close follow-up., (© 2024. The Author(s).)
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- 2024
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171. An ultrasound multiparametric method to quantify liver fat using magnetic resonance as standard reference.
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De Rosa L, Salvati A, Martini N, Chiappino D, Cappelli S, Mancini M, Demi L, Ghiadoni L, Bonino F, Brunetto MR, and Faita F
- Abstract
Background & Aims: There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference., Methods: Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis., Results: The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73)., Conclusions: Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)
- Published
- 2024
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172. A cellular disease model toward gene therapy of TGM1 -dependent lamellar ichthyosis.
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Sercia L, Romano O, Marini G, Enzo E, Forcato M, De Rosa L, and De Luca M
- Abstract
Lamellar ichthyosis (LI) is a chronic disease, mostly caused by mutations in the TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available, and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, such as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene-edited cells showed complete absence of transglutaminase 1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro . Using a self-inactivating γ-retroviral (SINγ-RV) vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1 -null keratinocytes displayed proper TG1 expression, enzymatic activity, and cornified envelope formation and, hence, restored proper epidermal architecture. Single-cell multiomics analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial for epidermal regeneration. This study serves as a proof of concept for assessing the potential of this therapeutic approach in treating TGM1 -dependent LI., Competing Interests: M.D.L. is a consultant for J-TEC-Japan Tissue Engineering, Ltd., (© 2024 The Author(s).)
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- 2024
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173. AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach.
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Rosignoli S, Lustrino E, Conci A, Fabrizi A, Rinaldo S, Latella MC, Enzo E, Prosseda G, De Rosa L, De Luca M, and Paiardini A
- Subjects
- Humans, Polymorphism, Single Nucleotide, Mutation, Software, Internet, Nucleotide Motifs, Camelids, New World genetics, Gene Editing methods, CRISPR-Cas Systems, Alleles
- Abstract
Gene therapy of dominantly inherited genetic diseases requires either the selective disruption of the mutant allele or the editing of the specific mutation. The CRISPR-Cas system holds great potential for the genetic correction of single nucleotide variants (SNVs), including dominant mutations. However, distinguishing between single-nucleotide variations in a pathogenic genomic context remains challenging. The presence of a PAM in the disease-causing allele can guide its precise targeting, preserving the functionality of the wild-type allele. The AlPaCas (Aligning Patients to Cas) webserver is an automated pipeline for sequence-based identification and structural analysis of SNV-derived PAMs that satisfy this demand. When provided with a gene/SNV input, AlPaCas can: (i) identify SNV-derived PAMs; (ii) provide a list of available Cas enzymes recognizing the SNV (s); (iii) propose mutational Cas-engineering to enhance the selectivity towards the SNV-derived PAM. With its ability to identify allele-specific genetic variants that can be targeted using already available or engineered Cas enzymes, AlPaCas is at the forefront of advancements in genome editing. AlPaCas is open to all users without a login requirement and is freely available at https://schubert.bio.uniroma1.it/alpacas., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2024
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174. Characterizing the Oligomers Distribution along the Aggregation Pathway of Amyloid Aβ1-40 by NMR.
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Pagano K, De Rosa L, Tomaselli S, Molinari H, D'Andrea LD, and Ragona L
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- Catechin chemistry, Catechin analogs & derivatives, Protein Aggregates, Humans, Alzheimer Disease metabolism, Nuclear Magnetic Resonance, Biomolecular methods, Magnetic Resonance Spectroscopy methods, Amyloid chemistry, Amyloid metabolism, Amyloid beta-Peptides chemistry, Amyloid beta-Peptides metabolism, Peptide Fragments chemistry, Peptide Fragments metabolism
- Abstract
This study delves into the early aggregation process of the Aβ1-40 amyloid peptide, elucidating the associated oligomers distribution. Motivated by the acknowledged role of small oligomers in the neurotoxic damage linked to Alzheimer's disease, we present an experimental protocol for preparing 26-O-acyl isoAβ1-40, a modified Aβ1-40 peptide facilitating rapid isomerization to the native amide form at neutral pH. This ensures seed-free solutions, minimizing experimental variability. Additionally, we demonstrate the efficacy of coupling NMR diffusion ordered spectroscopy (DOSY) with the Inverse Laplace Transform (ILT) reconstruction method, for effective characterization of early aggregation processes. This innovative approach efficiently maps oligomers distributions across a wide spectrum of initial peptide concentrations offering unique insights into the evolution of oligomers relative populations. As a proof of concept, we demonstrate the efficacy of our approach assessing the impact of Epigallocathechin gallate, a known remodeling agent of amyloid fibrils, on the oligomeric distributions of aggregated Aβ1-40. The DOSY-ILT proposed approach stands as a robust and discriminating asset, providing a powerful strategy for rapidly gaining insight into potential inhibitors' impact on the aggregation process., (© 2024 Wiley-VCH GmbH.)
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- 2024
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175. Development of a Culture-Common Formal Characteristics of Behavior - Temperament Markers Inventory (FCB-TMI-CC).
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Cyniak-Cieciura M, Popiel A, Zawadzki B, Cremeans-Smith JK, Alessandri G, Bielak P, Camino V, Cha EJ, Cho Y, Dobrowolski P, Fajkowska M, Filosa L, Fruehstorfer DB, Galarregui M, Goldfarb R, Hyun MH, Kalinina Z, Keegan E, Mambetalina A, McHugh L, Miracco M, Oshio A, Park C, Partarrieu A, De Rosa L, Sabirova R, Samekin A, Sánchez E, Sarno M, Tarruella C, Tulekova GM, and Topanova GT
- Abstract
The goal was to create a brief temperament inventory grounded in the Regulative Theory of Temperament (FCB-TMI-CC ) , with a user-friendly, online applicability for studies in different cultures. As the regulative role of temperament is strongly revealed under meaningful stress, the study was planned within the time of the COVID-19 pandemic. To ensure high diversity in terms of culture, economic and environmental conditions, data from nine countries (Poland, United States of America, Italy, Japan, Argentina, South Korea, Ireland, United Kingdom and Kazakhstan) were utilized (min. N = 200 per country). Validation data were gathered on the level of COVID-19 stressors, posttraumatic stress disorder (PTSD), depression, anxiety and stress symptoms, and Big Five personality traits. Multigroup confirmatory factor analysis served as the basis for the inventory's construction. The final culture-common version includes 37 items (5-6 in each of the 7 scales) and covers the core aspects of temperament dimensions. Temperament structure was confirmed to be equivalent across measured cultures. The measurement is invariant at the level of factor loadings and the reliability (internal consistency) and theoretical validity of the scales were at least acceptable. Therefore, the FCB-TMI-CC may serve as a valuable tool for studying temperament across diverse cultures and facilitate cross-cultural comparisons.
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- 2024
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176. Response to "Letter to the Editor: The Promise and Pitfalls of AI-Generated Anatomical Images: Evaluating Midjourney for Aesthetic Surgery Applications".
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Buzzaccarini G, De Rosa L, and Pagliardini L
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This response letter answers a query regarding our study on the use of the Midjourney app in aesthetic surgery. The original study questioned the utility of Midjourney in enhancing surgical skills, patient understanding, and communication effectiveness. The response highlights the challenges and potential of AI in medical visualization, advocating for meticulous development and evaluation. It stresses the importance of the scientific community's role in educating the public about the reliability and appropriate use of new technologies to avoid misconceptions and ensure the safe integration of AI in advancing medical fields like aesthetic surgery. The authors advocate for ongoing research and thoughtful application of AI tools, acknowledging both their benefits and limitations in the medical context.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)
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- 2024
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177. Deep Anterior Lamellar Keratoplasty Using Dehydrated versus Standard Organ Culture-Stored Donor Corneas: Prospective Randomized Trial.
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Bovone C, De Rosa L, Pellegrini M, Ruzza A, Ferrari S, Camposampiero D, Ponzin D, Zauli G, Yu AC, and Busin M
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- Humans, Prospective Studies, Male, Female, Adult, Middle Aged, Endothelium, Corneal pathology, Young Adult, Cornea surgery, Cell Count, Organ Culture Techniques, Corneal Transplantation methods, Tissue Donors, Visual Acuity physiology, Keratoconus surgery, Keratoconus physiopathology, Organ Preservation methods
- Abstract
Purpose: To compare the outcomes of deep anterior lamellar keratoplasty (DALK) using dehydrated versus standard organ culture-stored donor corneas for eyes with keratoconus., Design: Prospective, randomized, single-center trial conducted in Italy., Participants: Adult patients (age ≥ 18 years) with keratoconus scheduled for elective DALK., Methods: Patients undergoing successful type 1 bubble pneumatic dissection using a standard DALK technique were randomized during surgery to receive either dehydrated (n = 30) or standard organ culture-stored (n = 30) donor corneas., Main Outcome Measures: The primary study outcome was best spectacle-corrected visual acuity (BSCVA) 12 months after surgery. Secondary outcomes were refractive astigmatism (RA), endothelial cell density (ECD), and complication rates., Results: Postoperative BSCVA did not significantly differ between groups at both time points: mean difference at 6 months was 0.030 logarithm of the minimum angle of resolution (logMAR; 95% confidence interval [CI], -0.53 to 0.10 logMAR; P = 0.471) and at 12 months was -0.013 logMAR (95% CI, -0.10 to 0.08 logMAR; P = 0.764). No significant differences between groups were observed in terms of postoperative RA and ECD at all time points. In the first 3 days after DALK, an epithelial defect was present in 10 patients (33%) in the organ culture cornea group and in 29 patients (97%) in the dehydrated cornea group. Complete re-epithelialization was achieved by day 7 in all patients (100%) in both groups., Conclusions: The study provides evidence that the use of dehydrated corneas is noninferior to the use of standard organ culture donor corneas for DALK. Corneal tissue dehydration represents a viable solution that can allow long-term cornea preservation and avoid wastage of unused corneas., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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178. AXL receptor as an emerging molecular target in colorectal cancer.
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De Rosa L, Di Stasi R, Fusco V, and D'Andrea LD
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- Humans, Animals, Epithelial-Mesenchymal Transition, Drug Resistance, Neoplasm, Axl Receptor Tyrosine Kinase, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins antagonists & inhibitors, Receptor Protein-Tyrosine Kinases metabolism, Receptor Protein-Tyrosine Kinases antagonists & inhibitors, Molecular Targeted Therapy, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use
- Abstract
AXL receptor tyrosine kinase (AXL) is a receptor tyrosine kinase whose aberrant expression has recently been associated with colorectal cancer (CRC), contributing to tumor growth, epithelial-mesenchymal transition (EMT), increased invasiveness, metastatic spreading, and the development of drug resistance. In this review we summarize preclinical data, the majority of which are limited to recent years, convincingly linking the AXL receptor to CRC. These findings support the value of targeting AXL with molecules in drug discovery, offering novel and advanced therapeutic or diagnostic tools for CRC management., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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179. Clinical outcomes and complications of S53P4 bioactive glass in chronic osteomyelitis and septic non-unions: a retrospective single-center study.
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Gatti SD, Gaddi D, Turati M, Leone G, Arts JJ, Pessina F, Carminati M, Zatti G, De Rosa L, and Bigoni M
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- Humans, Retrospective Studies, Anti-Bacterial Agents therapeutic use, Persistent Infection, Bone Substitutes therapeutic use, Osteomyelitis drug therapy, Osteomyelitis surgery, Osteomyelitis microbiology
- Abstract
Introduction: Dead space management following debridement surgery in chronic osteomyelitis or septic non-unions is one of the most crucial and discussed steps for the success of the surgical treatment of these conditions. In this retrospective clinical study, we described the efficacy and safety profile of surgical debridement and local application of S53P4 bioactive glass (S53P4 BAG) in the treatment of bone infections., Methods: A consecutive single-center series of 38 patients with chronic osteomyelitis (24) and septic non-unions (14), treated with bioactive glass S53P4 as dead space management following surgical debridement between May 2015 and November 2020, were identified and evaluated retrospectively., Results: Infection eradication was reached in 22 out of 24 patients (91.7%) with chronic osteomyelitis. Eleven out of 14 patients (78.6%) with septic non-union achieved both fracture healing and infection healing in 9.1 ± 4.9 months. Three patients (7.9%) developed prolonged serous discharge with wound dehiscence but healed within 2 months with no further surgical intervention. Average patient follow-up time was 19.8 months ± 7.6 months., Conclusion: S53P4 bioactive glass is an effective and safe therapeutic option in the treatment of chronic osteomyelitis and septic non-unions because of its unique antibacterial properties, but also for its ability to generate a growth response in the remaining healthy bone at the bone-glass interface., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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180. Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells.
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Cattaneo C, Enzo E, De Rosa L, Sercia L, Consiglio F, Forcato M, Bicciato S, Paiardini A, Basso G, Tagliafico E, Paganelli A, Fiorentini C, Magnoni C, Latella MC, and De Luca M
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- Humans, Alleles, CRISPR-Cas Systems, Keratinocytes metabolism, Mutation, Stem Cells metabolism, Epidermolysis Bullosa Simplex genetics, Epidermolysis Bullosa Simplex therapy, Epidermolysis Bullosa Simplex metabolism
- Abstract
Epidermolysis bullosa simplex (EBS) is a rare skin disease inherited mostly in an autosomal dominant manner. Patients display a skin fragility that leads to blisters and erosions caused by minor mechanical trauma. EBS phenotypic and genotypic variants are caused by genetic defects in intracellular proteins whose function is to provide the attachment of basal keratinocytes to the basement membrane zone and most EBS cases display mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes. Besides palliative treatments, there is still no long-lasting effective cure to correct the mutant gene and abolish the dominant negative effect of the pathogenic protein over its wild-type counterpart. Here, we propose a molecular strategy for EBS01 patient's keratinocytes carrying a monoallelic c.475/495del21 mutation in KRT14 exon 1. Through the CRISPR-Cas9 system, we perform a specific cleavage only on the mutant allele and restore a normal cellular phenotype and a correct intermediate filament network, without affecting the epidermal stem cell, referred to as holoclones, which play a crucial role in epidermal regeneration., Competing Interests: Declaration of interests M.D.L. is co-founder and member of the Board of Directors of Holostem Terapie Avanzate (HTA) s.r.l in liquidation, Modena, Italy, as well as consultants for J-TEC-Japan Tissue Engineering, Ltd., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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181. Molecular Characterization of the Recombinant Ig1 Axl Receptor Domain: An Intriguing Bait for Screening in Drug Discovery.
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Di Stasi R, De Rosa L, Izzi G, and D'Andrea LD
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- Humans, Receptor Protein-Tyrosine Kinases chemistry, Proto-Oncogene Proteins metabolism, Ligands, Drug Discovery, Axl Receptor Tyrosine Kinase, Neoplasms
- Abstract
Axl receptor tyrosine kinase and its ligand Gas6 regulate several biological processes and are involved in both the onset and progression of tumor malignancies and autoimmune diseases. Based on its key role in these settings, Axl is considered a promising target for the development of molecules with therapeutic and diagnostic purposes. In this paper, we describe the molecular characterization of the recombinant Ig1 domain of Axl (Ig1 Axl) and its biochemical properties. For the first time, an exhaustive spectroscopic characterization of the recombinant protein through circular dichroism and fluorescence studies is also reported, as well as a binding analysis to its natural ligand Gas6, paving the way for the use of recombinant Ig1 Axl as a bait in drug discovery screening procedures aimed at the identification of novel and specific binders targeting the Axl receptor.
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- 2024
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182. Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).
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Ortí G, Gras L, Koster L, Kulagin A, Byrne J, Apperley JF, Halaburda K, Blau IW, Clark A, Kröger N, Griskevicius L, Carlson K, Collin M, Bloor A, Raiola AM, Blaise D, Aljurf M, López-Corral L, Sakellari I, Beguin Y, Wrobel T, de Rosa L, de Lavallade H, Hayden PJ, McLornan D, Chalandon Y, and Yakoub-Agha I
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- Adult, Humans, Chronic Disease, Cyclophosphamide therapeutic use, Retrospective Studies, Unrelated Donors, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid
- Abstract
Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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183. The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection.
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Cavallone D, Ornos EDB, Ricco G, Oliveri F, Coco B, Colombatto P, De Rosa L, Dalmacio LMM, Bonino F, and Brunetto MR
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- Humans, Hepatitis B virus physiology, Hepatitis B e Antigens, Hepatitis B Surface Antigens, Hepatitis B, Chronic, Hepatitis D, Chronic, MicroRNAs genetics
- Abstract
miRNAs circulating in whole serum and HBsAg-particles are differentially expressed in chronic hepatitis B (CHB) and HBeAg-negative-HBV infection (ENI); their profiles are unknown in chronic hepatitis D (CHD). Serum- and HBsAg-associated miRNAs were analyzed in 75 subjects of 3 well-characterized groups (CHB 25, CHD 25, ENI 25) using next-generation sequencing (NGS). Overall miRNA profiles were consonant in serum and HBsAg-particles but significantly different according to the presence of hepatitis independently of Hepatitis D Virus (HDV)-co-infection. Stringent (Bonferroni Correction < 0.001) differential expression analysis showed 39 miRNAs upregulated in CHB vs. ENI and 31 of them also in CHD vs. ENI. miRNA profiles were coincident in CHB and CHD with only miR-200a-3p upregulated in CHB. Three miRNAs (miR-625-3p, miR-142-5p, and miR-223-3p) involved in immune response were upregulated in ENI. All 3 hepatocellular miRNAs of MiR-B-Index (miR-122-5p, miR-99a-5p, miR-192-5p) were overexpressed in both CHB and CHD patients. In conclusion, CHD and CHB patients showed highly similar serum miRNA profiling that was significantly different from that of individuals with HBeAg-negative infection and without liver disease.
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- 2023
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184. Iatrogenic ophthalmic artery occlusion after platelet-rich plasma dermal filler documented with ultra-widefield imaging.
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Iovino C, Testa F, Cristiano L, De Rosa L, De Rosa G, and Simonelli F
- Abstract
Purpose: To report a case of iatrogenic ophthalmic artery occlusion (OAO) secondary to platelet-rich plasma (PRP) dermal filler injection for facial rejuvenation documented with ultra-widefield imaging., Methods: Case report., Results: A 45-year-old woman developed a sudden and painful vision loss in the left eye (LE) after a dermal filler injection of PRP in the left glabellar region. She immediately received intravenous corticosteroids with no improvements. Two weeks later a complete ophthalmological examination including visual acuity (VA), fundus examination, ultra-widefield fundus autofluorescence and fluorescein angiography, and optical coherence tomography was performed. A diagnosis of iatrogenic OAO in the LE with profound ocular ischemia was made and VA remained no light perception. Monthly follow-up visits were scheduled to ascertain the onset of any ocular complication., Conclusions: Dermal filler injections of PRP can lead to rare but devastating side effects with permanent visual loss. Considering that there is currently no validated treatment strategy, prevention could be the real key of iatrogenic OAO management., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2023
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185. Applications of Deep Learning Algorithms to Ultrasound Imaging Analysis in Preclinical Studies on In Vivo Animals.
- Author
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De Rosa L, L'Abbate S, Kusmic C, and Faita F
- Abstract
Background and Aim: Ultrasound (US) imaging is increasingly preferred over other more invasive modalities in preclinical studies using animal models. However, this technique has some limitations, mainly related to operator dependence. To overcome some of the current drawbacks, sophisticated data processing models are proposed, in particular artificial intelligence models based on deep learning (DL) networks. This systematic review aims to overview the application of DL algorithms in assisting US analysis of images acquired in in vivo preclinical studies on animal models., Methods: A literature search was conducted using the Scopus and PubMed databases. Studies published from January 2012 to November 2022 that developed DL models on US images acquired in preclinical/animal experimental scenarios were eligible for inclusion. This review was conducted according to PRISMA guidelines., Results: Fifty-six studies were enrolled and classified into five groups based on the anatomical district in which the DL models were used. Sixteen studies focused on the cardiovascular system and fourteen on the abdominal organs. Five studies applied DL networks to images of the musculoskeletal system and eight investigations involved the brain. Thirteen papers, grouped under a miscellaneous category, proposed heterogeneous applications adopting DL systems. Our analysis also highlighted that murine models were the most common animals used in in vivo studies applying DL to US imaging., Conclusion: DL techniques show great potential in terms of US images acquired in preclinical studies using animal models. However, in this scenario, these techniques are still in their early stages, and there is room for improvement, such as sample sizes, data preprocessing, and model interpretability.
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- 2023
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186. Benchmark methodological approach for the application of artificial intelligence to lung ultrasound data from COVID-19 patients: From frame to prognostic-level.
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Khan U, Afrakhteh S, Mento F, Fatima N, De Rosa L, Custode LL, Azam Z, Torri E, Soldati G, Tursi F, Macioce VN, Smargiassi A, Inchingolo R, Perrone T, Iacca G, and Demi L
- Subjects
- Humans, Prognosis, Benchmarking, Ultrasonography, Artificial Intelligence, COVID-19
- Abstract
Automated ultrasound imaging assessment of the effect of CoronaVirus disease 2019 (COVID-19) on lungs has been investigated in various studies using artificial intelligence-based (AI) methods. However, an extensive analysis of state-of-the-art Convolutional Neural Network-based (CNN) models for frame-level scoring, a comparative analysis of aggregation techniques for video-level scoring, together with a thorough evaluation of the capability of these methodologies to provide a clinically valuable prognostic-level score is yet missing within the literature. In addition to that, the impact on the analysis of the posterior probability assigned by the network to the predicted frames as well as the impact of temporal downsampling of LUS data are topics not yet extensively investigated. This paper takes on these challenges by providing a benchmark analysis of methods from frame to prognostic level. For frame-level scoring, state-of-the-art deep learning models are evaluated with additional analysis of best performing model in transfer-learning settings. A novel cross-correlation based aggregation technique is proposed for video and exam-level scoring. Results showed that ResNet-18, when trained from scratch, outperformed the existing methods with an F1-Score of 0.659. The proposed aggregation method resulted in 59.51%, 63.29%, and 84.90% agreement with clinicians at the video, exam, and prognostic levels, respectively; thus, demonstrating improved performances over the state of the art. It was also found that filtering frames based on the posterior probability shows higher impact on the LUS analysis in comparison to temporal downsampling. All of these analysis were conducted over the largest standardized and clinically validated LUS dataset from COVID-19 patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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187. Mechanical Thrombectomy in Cervical Artery Dissection-Related Stroke.
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Favruzzo F, De Rosa L, Salimbeni AF, Mozzetta S, Pieroni A, Viaro F, Cester G, Gabrieli JD, Causin F, Manara R, and Baracchini C
- Abstract
Background: Cervical artery dissection (CeAD) causing a large vessel occlusion (LVO) stroke might represent a procedural challenge for mechanical thrombectomy (MT) impacting on its effects. The aim of the present study was to analyze safety, reperfusion rates, and clinical outcome of patients with CeAD treated by MT and compare these results with those obtained in non-CeAD patients., Methods: All consecutive LVO stroke patients undergoing MT between June 2015 and June 2021 at our University Stroke Center were analyzed. Baseline and procedural characteristics, recanalization rates, adverse events, and functional outcome of patients with CeAD were compared with non-CeAD patients., Results: MT was performed on 375 patients, 20 (5.3%) were diagnosed with CeAD. These patients were younger (52.9 ± 7.8 vs. 72.5 ± 12.9 years, P < 0.001), and showed lower rates of cardiovascular risk factors. In patients with CeAD, tandem occlusions were more frequent (65.0% vs. 14.4%, P < 0.001), groin to reperfusion time was longer (93.6 ± 34.9 vs. 68.3 ± 50.2 minutes, P = 0.01), and general anesthesia was more frequently utilized (70.0% vs. 27.9%, P < 0.001). Recanalization rates (Treatment in Cerebral Infarction 2b-3: 100.0% vs. 88.5%) and MT-related adverse events (10.0% vs. 10.7%) did not differ between the groups, while functional outcome was better in patients with CeAD (modified Rankin Scale 0-2 at 3 months: 85.0% vs. 62.0%, P = 0.038)., Conclusions: Although CeAD represents a procedural challenge, MT constitutes a safe and effective treatment for patients with CeAD with LVO stroke., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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188. Structure-Based Design of Peptides Targeting VEGF/VEGFRs.
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Di Stasi R, De Rosa L, and D'Andrea LD
- Abstract
Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a main role in the regulation of angiogenesis and lymphangiogenesis. Furthermore, they are implicated in the onset of several diseases such as rheumatoid arthritis, degenerative eye conditions, tumor growth, ulcers and ischemia. Therefore, molecules able to target the VEGF and its receptors are of great pharmaceutical interest. Several types of molecules have been reported so far. In this review, we focus on the structure-based design of peptides mimicking VEGF/VEGFR binding epitopes. The binding interface of the complex has been dissected and the different regions challenged for peptide design. All these trials furnished a better understanding of the molecular recognition process and provide us with a wealth of molecules that could be optimized to be exploited for pharmaceutical applications.
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- 2023
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189. Contemporary role of amputation for patients with extremity soft tissue sarcoma.
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Conti L, Buriro F, Baia M, Pasquali S, Miceli R, De Rosa L, Gronchi A, and Fiore M
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- Humans, Aged, Extremities surgery, Extremities pathology, Amputation, Surgical, Upper Extremity, Neoplasm Recurrence, Local pathology, Sarcoma surgery, Sarcoma pathology, Soft Tissue Neoplasms pathology, Orthopedic Procedures
- Abstract
Introduction: limb-sparing surgery is the mainstream treatment for primary extremity soft tissue sarcoma (ESTS) at referral centers, following advances in surgical reconstructions and multimodal management. However, amputation is still needed in selected patients and has not yet been described for a ESTS cohort in a contemporary scenario., Material and Methods: consecutive patients who underwent surgery for primary ESTS from 2006 to 2018 were extracted from a prospectively collected database at our reference center. Patients receiving amputation for either primary tumor or local recurrence (LR) after limb-sparing surgery were selected for analysis., Results: Among 1628 primary ESTS, 29 patients underwent primary amputation (1.8%), 22/1159 (1.9%) for upper limb and 7/469 (1.5%) for lower limb ESTS. Patients were mainly affected by grade III FNCLCC (89.6%) of notable dimension (median size 16 cm, IQR 10-24). 65.5% of patients received preoperative treatments (systemic or regional chemotherapy, radiotherapy or chemo-radiation). Secondary amputation for LR was performed after a median of 23 months in 16/1599 patients (1%). Median survival time was 16.2 and 29.6 months after primary or secondary amputation respectively. Factors prompting the need for a primary amputation were most often a combination of multifocal disease, bone invasion and pain or neurovascular bundle involvement and relevant comorbidities, mainly for grade III tumors in elderly patients., Conclusion: Contemporary rate of amputation for ESTS at a reference center is extremely low. Still, amputation is required in selected cases with advanced presentations, especially in elderly, frail patients., Competing Interests: Declaration of competing interest The Authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
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- 2023
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190. A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes.
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De Rosa L, Hawala I, Di Stasi R, Stefania R, Capozza M, Nava D, and D'Andrea LD
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- Maleimides chemical synthesis, Maleimides chemistry, Peptides, Sulfhydryl Compounds
- Abstract
Multimodality probes appear of great interest for innovative imaging applications in disease diagnosis. Herein, we present a chemical strategy enabling site-specific double-modification and cyclization of a peptide probe exploiting native chemical ligation (NCL) and thiol-maleimide addition. The synthetic strategy is straightforward and of general applicability for the development of double-labeled peptide multimodality probes.
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- 2023
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191. Stairways to Advanced Therapies for Epidermolysis Bullosa.
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De Rosa L, Enzo E, Palamenghi M, Sercia L, and De Luca M
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- Humans, Epidermis, Phenotype, Epidermolysis Bullosa therapy
- Abstract
Epidermolysis bullosa (EB) is a devastating genetic skin disease typified by a plethora of different phenotypes and ranking from severe, early lethal, to mild localized forms. Although there is no cure for EB, recent progress in pharmacology and molecular and cellular biology is boosting the development of new advanced therapeutic strategies. Here we will focus on two main categories of such therapies: (1) those aimed at controlling inflammation and inducing reepithelialization of the wounds, and (2) those, perhaps more challenging and ambitious, that aim to permanently regenerate a fully functional epidermis, which requires targeting of epidermal stem cells. In both cases, the genetic variants underlying the different EB forms and factors, such as genetic background, modifier genes, comorbidities, and lifestyle, all of which impinge on EB genotype-phenotype correlation, need to be defined., (Copyright © 2023 Cold Spring Harbor Laboratory Press; all rights reserved.)
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- 2023
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192. The "SALPARE study" of spontaneous intracerebral hemorrhage: part 1.
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De Rosa L, Manara R, Vodret F, Kulyk C, Montano F, Pieroni A, Viaro F, Zedde ML, Napoletano R, Ermani M, and Baracchini C
- Abstract
Background: Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke with a huge impact on patients and families. Expanded use of oral anticoagulants and ageing population might contribute to an epidemiological change. In view of these trends, we planned a study to obtain a contemporary picture and identify early prognostic factors to improve secondary prevention., Methods: This multicenter prospective cohort study included consecutive adult patients with non-traumatic ICH admitted to three academic Italian hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Demographic characteristics, vascular risk profile, clinical data and main radiological characteristics were correlated to 90-day clinical outcome., Results: Out of 682 patients [mean age: 73 ± 14 years; 316 (46.3%) females] enrolled in this study, 40% died [86/180 (47.8%) in Salerno, 120/320 (37.5%) in Padova, 67/182 (36.8%) in Reggio Emilia; p < 0.05)] and 36% were severely disabled at 90 days. Several factors were associated with a higher risk of poor functional outcome such as antithrombotic drug use, hyperglycemia, previous cerebrovascular accident, low platelet count, and pontine/massive/intraventricular hemorrhage. However, at multivariate analysis only pre-ICH mRS score (OR 30.84), GCS score at presentation (OR 11.88), initial hematoma volume (OR 29.71), and NIHSS score at presentation (OR 25.89) were independent predictors of death and poor functional outcome., Conclusion: Despite the heterogeneity among centers, this study on ICH has identified four simple prognostic factors that can independently predict patients outcome, stratify their risk, and guide their management., (© 2023. The Author(s).)
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- 2023
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193. The "SALPARE study" of spontaneous intracerebral haemorrhage-part 2-early CT predictors of outcome in ICH: keeping it simple.
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Manara R, De Rosa L, Vodret F, Kulyk C, Pennella R, Contrino E, Cester G, Causin F, Pieroni A, Viaro F, Zedde ML, Pascarella R, Napoletano R, and Baracchini C
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Background: The aim of this study was to investigate the prognostic role of hematoma characteristics and hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH)., Methods: This multicenter prospective cohort study enrolled consecutive adult patients with non-traumatic ICH admitted to three Italian academic hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Early noncontrast CT (NCCT) features of the hematoma, including markers of HE, and 3-month outcome were recorded. Multivariable logistic regression analysis was performed to identify predictors of poor outcome., Results: A total of 682 patients were included in the study [mean age: 73 ± 14 years; 316 (46.3%) females]. Pontine and massive hemorrhage, intraventricular bleeding, baseline hematoma volume > 15 mL, blend sign, swirl sign, margin irregularity ≥ 4, density heterogeneity ≥ 3, hypodensity ≥ 1, island sign, satellite sign, and black hole sign were associated with a higher risk of mortality and disability. However, at multivariate analysis only initial hematoma volume (OR 29.71) proved to be an independent predictor of poor functional outcome at 3 months., Conclusion: Simple hematoma volume measured on baseline CT best identifies patients with a worse outcome, while early NCCT markers of HE do not seem to add any clinically significant information., (© 2022. The Author(s).)
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- 2023
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194. Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: pre-planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial.
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Mina R, Musto P, Rota-Scalabrini D, Paris L, Gamberi B, Palmas A, Aquino S, de Fabritiis P, Giuliani N, De Rosa L, Gozzetti A, Cellini C, Bertamini L, Capra A, Oddolo D, Vincelli ID, Ronconi S, Pavone V, Pescosta N, Cea M, Fioritoni F, Ballanti S, Grasso M, Zamagni E, Belotti A, Boccadoro M, and Gay F
- Subjects
- Male, Humans, Female, Lenalidomide, Neoplasm, Residual, Dexamethasone, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Cytogenetic Analysis, Transplantation, Autologous methods, Multiple Myeloma drug therapy, Multiple Myeloma genetics, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Background: Patients with newly diagnosed multiple myeloma and high-risk cytogenetic abnormalities (HRCA) represent an unmet medical need. In the FORTE trial, lenalidomide and dexamethasone plus carfilzomib (KRd) induction resulted in a higher proportion of patients with at least a very good partial response as compared with carfilzomib, cyclophosphamide, and dexamethasone (KCd), and carfilzomib plus lenalidomide maintenance prolonged progression-free survival compared with lenalidomide maintenance. In this prespecified analysis of the FORTE trial, we described the outcomes of enrolled patients according to their cytogenetic risk., Methods: The UNITO-MM-01/FORTE was a randomised, open-label, phase 2 trial done at 42 Italian academic and community practice centres, which enrolled transplant-eligible patients with newly diagnosed multiple myeloma aged 18-65 years. Eligible patients had newly diagnosed multiple myeloma based on standard International Myeloma Working Group criteria, a Karnofsky performance status of at least 60%, and had not received any previous treatment with anti-myeloma therapy. At enrolment, patients were stratified according to International Staging System stage (I vs II/III) and age (<60 years vs 60-65 years) and randomly assigned (1:1:1) to KRd plus autologous stem-cell transplantation (ASCT; four 28-day induction cycles with KRd, melphalan at 200 mg/m
2 and ASCT [MEL200-ASCT], followed by four 28-day KRd consolidation cycles), 12 28-day KRd cycles, or KCd plus ASCT (four 28-day induction cycles with KCd, MEL200-ASCT, and four 28-day KCd consolidation cycles), using a web-based system (block randomisation, block size of 12). Carfilzomib was administered at 20 mg/m2 on days 1 and 2 of cycle 1, followed by 36 mg/m2 intravenously administered on days 8, 9, 15, and 16 of cycle 1, and then 36 mg/m2 intravenously administered for all subsequent doses on days 1, 2, 8, 9, 15, 16; lenalidomide 25 mg was administered orally on days 1-21; cyclophosphamide 300 mg/m2 was administered orally on days 1, 8, and 15; and dexamethasone 20 mg was administered orally or intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23. After the consolidation phase, patients were stratified according to induction-consolidation treatment and randomly assigned (1:1; block size of 8) to maintenance treatment with carfilzomib plus lenalidomide or lenalidomide alone. Carfilzomib 36 mg/m2 was administered intravenously on days 1-2 and days 15-16, every 28 days for up to 2 years, and lenalidomide 10 mg was administered orally on days 1-21 every 28 days until progression or intolerance in both groups. The primary endpoints were the proportion of patients with at least a very good partial response after induction with KRd versus KCd and progression-free survival with carfilzomib plus lenalidomide versus lenalidomide alone as maintenance treatment. In this preplanned analysis, we included patients enrolled in the FORTE trial with complete cytogenetic data on del(17p), t(4;14), t(14;16), del(1p), gain(1q) (3 copies), and amp(1q) (≥4 copies) assessed by fluorescence in-situ hybridisation analysis on CD138-positive sorted cells. We assessed progression-free survival, overall survival, minimal residual disease negativity, and 1-year sustained minimal residual disease negativity according to the presence of zero, one, and two or more HRCA across treatment groups. The FORTE trial is ongoing, and registered with ClinicalTrials.gov, NCT02203643., Findings: Between Feb 23, 2015, and April 5, 2017, 477 patients were enrolled, of whom 396 (83%) had complete cytogenetic data and were analysed (176 [44%] of whom were women and 220 [56%] were men). The median follow-up from first randomisation was 51 months (IQR 46-56). 4-year progression-free survival was 71% (95% CI 64-78) in patients with zero HRCA, 60% (95% CI 52-69) in patients with one HRCA, and 39% (95% CI 30-50) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of progression or death was similar in patients with one HRCA (hazard ratio [HR] 1·33 [95% CI 0·90-1·97]; p=0·15) and higher in patients with two or more HRCA (HR 2·56 [95% CI 1·74-3·75]); p<0·0001) across the induction-intensification-consolidation groups. Moreover, the risk of progression or death was also higher in patients with two or more HRCA versus those with one HRCA (HR 1·92 [95% CI 1·34-2·76]; p=0·0004). 4-year overall survival from the first randomisation was 94% (95% CI 91-98) in patients with zero HRCA, 83% (95% CI 76-90) in patients with one HRCA, and 63% (95% CI 54-74) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of death was significantly higher in patients with one HRCA (HR 2·55 [95% CI 1·22-5·36]; p=0·013) and two or more HRCA (HR 6·53 [95% CI 3·24-13·18]; p<0·0001). Patients with two or more HRCA also had a significantly higher risk of death than those with one HRCA (HR 2·56 [95% CI 1·53-4·28]; p=0·0004). The rates of 1-year sustained minimal residual disease negativity were similar in patients with zero HRCA (53 [35%] of 153] and with one HRCA (57 [41%] of 138) and were lower in patients with two or more HRCA (25 [24%] of 105). The median duration of follow-up from second randomisation was 37 months (IQR 33-42). 3-year progression-free survival from the second randomisation was 80% (95% CI 74-88) in patients with zero HRCA, 68% (95% CI 59-78) in patients with one HRCA, and 53% (95% CI 42-67) in patients with two or more HRCA. The risk of progression or death was higher in patients with one HRCA (HR 1·68 [95% CI 1·01-2·80]; p=0·048) and two or more HRCA (2·74 [95% CI 1·60-4·69], p=0·0003) than in patients with zero HRCA., Interpretation: This preplanned analysis of the FORTE trial showed that carfilzomib-based induction-intensification-consolidation regimens are effective strategies in patients with standard risk (zero HRCA) and high-risk (one HRCA) myeloma, resulting in similar rates of progression-free survival and 1-year sustained minimal residual disease negativity. Despite promising progression-free survival, patients with ultra-high-risk disease (those with 2 or more HRCA) still have an increased risk of progression and death and therefore represent an unmet medical need., Funding: Amgen and Celgene/Bristol Myers Squibb., Competing Interests: Declaration of interests RM has received honoraria from Janssen, Celgene, Takeda, and Amgen; has served on the advisory boards for Janssen, Celgene, Takeda, Bristol Myers Squibb, and Amgen; and has received consultancy fees from Janssen, Takeda, and Sanofi. PM has received honoraria from Celgene, Janssen, Takeda, Bristol Myers Squibb, Amgen, Novartis, Gilead, Jazz, Sanofi, AbbVie, and GlaxoSmithKlin; and has served on scientific advisory boards for Celgene, Janssen, Takeda, Bristol Myers Squibb, Amgen, Jazz, Sanofi, AbbVie, and GlaxoSmithKline. LP has received honoraria from Celgene, Takeda, Amgen, Bristol Myers Squibb, and Janssen; has served on the advisory boards for Celgene, Bristol Myers Squibb, Amgen, and Janssen; and has received consultancy fees from Janssen. BG has received honoraria from Amgen, Bristol Myers Squibb, Janssen, and Takeda; and has served on the advisory boards for Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and Takeda. AP has served on the advisory board for Amgen; has received support for meeting fees, travel, and lodging expenses from Amgen, Celgene, and Janssen; and has received non-financial support from Celgene, Janssen, Roche, Takeda, and Amgen. NG has received research grants from Celgene and Janssen Pharmaceutical; has received sponsorship for clinical studies from Janssen Pharmaceutical and Millennium Pharmaceutical; has served on the advisory boards for Celgene, Takeda, and Janssen Pharmaceutical; and has received support for attending meetings from Janssen Pharmaceutical, Celgene, and Bristol Myers Squibb. AG has received honoraria from Celgene, Takeda, Amgen, and Janssen; and has served on the advisory boards for Takeda and Janssen. MC has received advisory fees from Celgene, Janssen, and Takeda; and has received research funding from Celgene. SB has received honoraria from Sanofi, Celgene, Takeda, and Janssen. EZ has received honoraria from and served on the advisory boards for Janssen, Bristol Myers Squibb, Takeda, Sanofi, Amgen, GlaxoSmithKline, and Oncopeptides. AB has served on the advisory boards for Amgen, Janssen, Celgene, GlaxoSmithKline, and Takeda. MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and AbbVie; has served on the advisory boards for Janssen and GlaxoSmithKline; and has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Mundipharma. FG has received honoraria from Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, and GlaxoSmithKline; and has served on the advisory boards for Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, GlaxoSmithKline, Roche, Adaptive Biotechnologies, Oncopeptides, bluebird bio, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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195. Non-Union Scoring System (NUSS): Is It Enough in Clinical Practice?
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Gaddi D, Gatti SD, Piatti M, Poli A, De Rosa L, Riganti A, Zatti G, Bigoni M, and Turati M
- Abstract
Introduction: Bone consolidation defects represent a real orthopedic challenge because of the absence of validated treatment guidelines that can assist the surgeon in his choices. The aim of this study is to evaluate the appropriateness of the Non-Union Scoring System NUSS treatment protocol in the management of long bone non-unions by comparing it to the experience-based therapeutic approach carried out in our facility., Materials and Methods: We conducted a comparative outcome study of a retrospective series of 89 patients surgically treated for long bone non-union in our facility vs. clinical results reported by Calori et al. obtained following the NUSS treatment protocol., Results: Radiographic healing was reached in 13/13 non-unions (100%) in group NUSS 1, in 58/62 (93.5%) in group NUSS 2, and in 13/14 (92.9%) in group NUSS 3. The mean time to radiographic healing was 5.69 ± 2.09 months in group 1, 7.38 ± 3.81 months in group 2 and 9.23 ± 2.31 months in group 3. 91% of patients in group I, 69% in group II and 48% in group III received what would be considered by the NUSS treatment protocol an "overtreatment", especially from a biological stand point. The comparative outcome analysis shows that our case series achieved significantly higher global healing rates ( p value = 0.017) and shorter radiological healing times in groups NUSS 1 and 2 ( p value < 0.001)., Conclusion: From the results obtained, we can assume that the NUSS treatment protocol might underestimate the necessary therapies, particularly from a biological point of view., Competing Interests: Conflict of InterestsThe authors declare that they have no conflicts of interest concerning this article. No financial support has been received by the authors for the preparation of this paper., (© The Author(s) 2022.)
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- 2022
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196. Switching the N-Capping Region from all-L to all-D Amino Acids in a VEGF Mimetic Helical Peptide.
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De Rosa L, Diana D, Capasso D, Stefania R, Di Stasi R, Fattorusso R, and D'Andrea LD
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- Amino Acid Sequence, Peptides chemistry, Circular Dichroism, Protein Conformation, Amino Acids, Vascular Endothelial Growth Factor A
- Abstract
The N-capping region of an α-helix is a short N-terminal amino acid stretch that contributes to nucleate and stabilize the helical structure. In the VEGF mimetic helical peptide QK, the N-capping region was previously demonstrated to be a key factor of QK helical folding. In this paper, we explored the effect of the chiral inversion of the N-capping sequence on QK folding, performing conformational analysis in solution by circular dichroism and NMR spectroscopy. The effect of such a modification on QK stability in serum and the proliferative effect were also evaluated.
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- 2022
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197. Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!
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Riccardi C, D'Aria F, Fasano D, Digilio FA, Carillo MR, Amato J, De Rosa L, Paladino S, Melone MAB, Montesarchio D, and Giancola C
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- Humans, Huntingtin Protein genetics, Aptamers, Nucleotide pharmacology, Aptamers, Nucleotide chemistry, Neuroblastoma, G-Quadruplexes, Huntington Disease
- Abstract
Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington's disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.
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- 2022
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198. The steep uphill path leading to ex vivo gene therapy for genodermatoses.
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Palamenghi M, De Luca M, and De Rosa L
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- Cell- and Tissue-Based Therapy, Humans, Regenerative Medicine, Tissue Engineering, Gene Editing, Genetic Therapy adverse effects
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Cell therapy, gene therapy, and tissue engineering have the potential to revolutionize the field of regenerative medicine. In particular, gene therapy is understood as the therapeutical correction of mutated genes by addition of a correct copy of the gene or site-specific gene modifications. Gene correction of somatic stem cells sustaining renewing tissues is critical to ensure long-term clinical success of ex vivo gene therapy. To date, remarkable clinical outcomes arose from combined ex vivo cell and gene therapy of different genetic diseases, such as immunodeficiencies and genodermatoses. Despite the efforts of researchers around the world, only a few of these advanced approaches have yet made it to routine therapy. In fact, gene therapy poses one of the greatest technical challenges in modern medicine, spanning safety and efficacy issues, regulatory constraints, registration and market access, all of which need to be addressed to make the therapy available to patients with rare disease. In this review, we survey some of the main challenges in the development of combined cell and gene therapy of genetic skin diseases.
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- 2022
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199. The joint battle to tackle epidermolysis bullosa through gene therapy.
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De Rosa L and De Luca M
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- Genetic Therapy, Humans, Epidermolysis Bullosa genetics, Epidermolysis Bullosa therapy
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Efforts are dedicated to definitively tackle skin lesions plaguing patients with epidermolysis bullosa (EB), a devastating genetic disorder affecting the integumentary system. Both in vivo gene therapy, as recently reported by Gurevich et al., and combined ex vivo cell and gene therapy strategies are under investigation. Here, we address the advantages and disadvantages of these different approaches., Competing Interests: Declaration of interests M.D.L. is a co-founder and member of the Board of Directors of Holostem Terapie Avanzate, s.r.l., Modena, Italy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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200. Down Syndrome Fetal Fibroblasts Display Alterations of Endosomal Trafficking Possibly due to SYNJ1 Overexpression.
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De Rosa L, Fasano D, Zerillo L, Valente V, Izzo A, Mollo N, Amodio G, Polishchuk E, Polishchuk R, Melone MAB, Criscuolo C, Conti A, Nitsch L, Remondelli P, Pierantoni GM, and Paladino S
- Abstract
Endosomal trafficking is essential for cellular homeostasis. At the crossroads of distinct intracellular pathways, the endolysosomal system is crucial to maintain critical functions and adapt to the environment. Alterations of endosomal compartments were observed in cells from adult individuals with Down syndrome (DS), suggesting that the dysfunction of the endosomal pathway may contribute to the pathogenesis of DS. However, the nature and the degree of impairment, as well as the timing of onset, remain elusive. Here, by applying imaging and biochemical approaches, we demonstrate that the structure and dynamics of early endosomes are altered in DS cells. Furthermore, we found that recycling trafficking is markedly compromised in these cells. Remarkably, our results in 18-20 week-old human fetal fibroblasts indicate that alterations in the endolysosomal pathway are already present early in development. In addition, we show that overexpression of the polyphosphoinositide phosphatase synaptojanin 1 (Synj1) recapitulates the alterations observed in DS cells, suggesting a role for this lipid phosphatase in the pathogenesis of DS, likely already early in disease development. Overall, these data strengthen the link between the endolysosomal pathway and DS, highlighting a dangerous liaison among Synj1, endosomal trafficking and DS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Rosa, Fasano, Zerillo, Valente, Izzo, Mollo, Amodio, Polishchuk, Polishchuk, Melone, Criscuolo, Conti, Nitsch, Remondelli, Pierantoni and Paladino.)
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- 2022
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