265 results on '"Vittoria, V."'
Search Results
2. Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells.
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Forte M, Marchitti S, di Nonno F, Pietrangelo D, Stanzione R, Cotugno M, D'Ambrosio L, D'Amico A, Cammisotto V, Sarto G, Rocco E, Simeone B, Schiavon S, Vecchio D, Carnevale R, Raffa S, Frati G, Volpe M, Sciarretta S, and Rubattu S more...
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- Humans, Receptors, Atrial Natriuretic Factor metabolism, Receptors, Atrial Natriuretic Factor genetics, Tumor Necrosis Factor-alpha pharmacology, Tumor Necrosis Factor-alpha metabolism, Stress, Physiological drug effects, Signal Transduction drug effects, Atrial Natriuretic Factor metabolism, Atrial Natriuretic Factor pharmacology, Autophagy drug effects, Human Umbilical Vein Endothelial Cells metabolism
- Abstract
Atrial natriuretic peptide (ANP), a cardiac hormone involved in the regulation of water/sodium balance and blood pressure, is also secreted by endothelial cells, where it exerts protective effects in response to stress. Autophagy is an intracellular self-renewal process involved in the degradation of dysfunctional cytoplasmic elements. ANP was recently reported to act as an extracellular regulator of cardiac autophagy. However, its role in the regulation of endothelial autophagy has never been investigated. Here, we tested the effects of ANP in the regulation of autophagy in human umbilical vein endothelial cells (HUVECs). We found that ANP rapidly increases autophagy and autophagic flux at physiological concentrations through its predominant pathway, mediated by natriuretic peptide receptor type A (NPR-A) and protein kinase G (PKG). We further observed that ANP is rapidly secreted by HUVEC under stress conditions, where it mediates stress-induced autophagy through autocrine and paracrine mechanisms. Finally, we found that the protective effects of ANP in response to high-salt loading or tumor necrosis factor (TNF)-α are blunted by concomitant inhibition of autophagy. Overall, our results suggest that ANP acts as an endogenous autophagy activator in endothelial cells. The autophagy mechanism mediates the protective endothelial effects exerted by ANP., Competing Interests: Declaration of competing interest None to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2025
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3. Survival of dental implants placed in a postgraduate educational setting: a retrospective cohort study.
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Caponio VCA, Sharma A, Musella G, Perrotti V, and Quaranta A
- Abstract
Introduction: Dental implant treatment can still fail due to various factors. The aim of this retrospective cohort study was to assess the influence of operator experience in a postgraduate educational setting, as well as patient, implant, and surgical risk factors on the incidence of the dental implant failure., Methods: The dental records of 1049 implants with a mean follow-up of 794.70 days were analysed. Variables included operator experience (year of specialty study) and clinic-pathological patients' related variables. Clinic-pathological associations were explored and a Cox regression model accounted for implant survival factors., Results: Multivariate analysis revealed that a history of periodontitis and smoking were the only factors with independent prognostic value, with hazard ratios of 2.0 (95 % CI: 1.0-4.0, p = 0.048) and 1.9 (95 % CI: 1.0-3.6, p = 0.039) respectively. Conversely, despite implant treatment delivered by early career students had a higher failure rate (5.6 %) compared to advanced career students (3.7 %), this difference was statistically significant only in the univariate analysis., Conclusion: Periodontitis and smoking are independent prognostic variables, with career level potentially biasing complex case allocation to advanced students. Targeted educational interventions, including virtual reality and artificial intelligence, should be emphasized in student training. University-based implant trials must consider operator career stage., Clinical Significance: The study underscores the importance of operator experience in dental implant success. It highlights that while clinical experience influences outcomes, factors like a history of periodontitis and smoking are independent predictors of implant failure. These findings emphasize the need for targeted educational interventions to improve clinical training and patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.) more...
- Published
- 2024
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4. The role of diagnostic laparoscopy in locally advanced cervical cancer staging.
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Bizzarri N, Pedone Anchora L, Teodorico E, Certelli C, Galati G, Carbone V, Gallotta V, Naldini A, Costantini B, Querleu D, Fanfani F, Fagotti A, Scambia G, and Ferrandina G
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- Humans, Female, Middle Aged, Retrospective Studies, Adult, Aged, Prognosis, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms diagnostic imaging, Laparoscopy, Neoplasm Staging, Positron Emission Tomography Computed Tomography, Peritoneal Neoplasms secondary, Peritoneal Neoplasms diagnostic imaging, Magnetic Resonance Imaging
- Abstract
Objective: Peritoneal involvement may be overlooked in patients with locally advanced cervical cancer (LACC). This may lead to underestimation of prognosis and to undertreatment limited to locoregional disease locations. However, staging laparoscopy in LACC is not routinely performed. The primary aim of this study was to determine the proportion of peritoneal metastasis by laparoscopy and the factors associated with peritoneal metastasis in patients with LACC. Secondary aims were to evaluate the performance of staging imaging in detecting peritoneal disease and the prognosis of patients with peritoneal metastasis., Methods: Retrospective single-institution study including consecutive patients with newly diagnosed LACC (FIGO 2018 stage IB3 and IIA2-IVA) between 06/2015 and 06/2020. All women underwent PET/CT scan, MRI scan and diagnostic laparoscopy at the time of examination under anesthesia (EUA), as part of cervical cancer staging. Peritoneal metastasis was histologically confirmed in all cases., Results: 251 patients were included. 33 (13.2 %) had peritoneal metastasis. The treatment plan was changed for 28/33 (84.8 %) patients with peritoneal metastasis (11.1 % of the entire LACC cohort). Multivariate analysis demonstrated that grade 3 (OR:1.572, 95%CI:1.021-2.419; p = 0.040) and AJCC stage T3-4 (OR:3.435, 95%CI:1.482-7.960; p = 0.004) were variables associated with increased risk of peritoneal metastasis. Sensitivity of PET/CT-scan and MRI-scan in detecting peritoneal metastasis was 4.5 % (95%CI:0.1-22.8) and 13.8 % (95%CI:3.9-31.7), respectively. Peritoneal metastasis was independently associated with worse PFS and OS (HR:3.008, 95%CI:1.779-5.087, p < 0.001 and HR:4.078, 95%CI:2.232-7.451; p < 0.001, respectively)., Conclusion: LACC patients with grade 3 histology and/or AJCC stage T3-4 had high-risk of peritoneal metastasis and diagnostic laparoscopy might be considered as part of cervical cancer staging in these patients. Peritoneal metastasis was an independent factor associated with worse PFS and OS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2024
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5. Metabolic and hepatic phenotypes in sarcopenic obesity and impact of bariatric surgery.
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Zambon Azevedo V, Bel Lassen P, Aron-Wisnewsky J, Genser L, Charlotte F, Bedossa P, Ponnaiah M, Pais R, Clément K, Oppert JM, and Ratziu V
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- Humans, Female, Male, Middle Aged, Adult, Diabetes Mellitus, Type 2 complications, Liver metabolism, Absorptiometry, Photon, Fatty Liver physiopathology, Body Composition, Bariatric Surgery methods, Sarcopenia epidemiology, Weight Loss, Phenotype, Obesity surgery, Obesity complications, Obesity physiopathology
- Abstract
Background & Aims: Sarcopenic obesity (SO) is associated with cardiometabolic disorders and steatotic liver disease and carries major health risks. We assessed the hepatic and metabolic clinical phenotype associated with SO in patients with obesity undergoing bariatric surgery (BS). We also evaluated whether weight-loss and metabolic improvement post-surgery differ between patients with and without SO., Methods: 972 consecutive patients from a single-center BS cohort who underwent whole-body dual-energy X-ray absorptiometry (DXA) and peri-operative liver biopsy were included. SO was diagnosed using the AIM-SO score, an AI-assisted unbiased clustering algorithm based on body composition. One-year post-surgery, 862 patients were reassessed for AIM-SO score changes., Results: Pre-operatively, 207 (21.3 %) patients were diagnosed with SO. These patients had significantly higher prevalence of type-2 diabetes (T2D), arterial hypertension and obstructive sleep apnea (OSA) compared to patients without SO (all p ≤ 0.003). Patients with SO had more severe liver damage: higher grades of moderate/advanced steatosis (64.2 % vs. 47.3 %), steatohepatitis (44.4 % vs. 32.3 %) and advanced fibrosis (12.1 % vs. 6.0 %) (all p ≤ 0.01). One-year post-BS, 58.5 % of patients had remission of SO. Patients with persistent SO exhibited less weight-loss than those with SO remission (-23.8 kg vs. -29.1 kg, p < 0.001) and had lower rates of remission for T2D (41.9 % vs. 69.8 %), arterial hypertension (20.8 % vs. 45.3 %), and metabolic syndrome (47.6 % vs. 75.0 %) (all p ≤ 0.009)., Conclusion: The DXA-based AIM-SO score identifies patients with SO who are at greater risk of hepatic and cardiometabolic comorbidities, and predicts less favorable weight-loss and metabolic improvements post-BS., Competing Interests: Conflict of interest None., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.) more...
- Published
- 2024
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6. Inflammatory plasma profile in genetic symptomatic and presymptomatic Frontotemporal Dementia - A GENFI study.
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Fenoglio C, Serpente M, Arcaro M, Carandini T, Sacchi L, Pintus M, Rotondo E, Borracci V, Ghezzi L, Bouzigues A, Russell LL, Foster PH, Ferry-Bolder E, van Swieten JC, Jiskoot LC, Seelaar H, Sánchez Valle R, Laforce R, Graff C, Vandenberghe R, de Mendonça A, Tiraboschi P, Santana I, Gerhard A, Levin J, Sorbi S, Otto M, Pasquier F, Ducharme S, Butler CR, Ber IL, Finger E, Carmela Tartaglia M, Masellis M, Rowe JB, Synofzik M, Moreno F, Borroni B, Rohrer JD, Arighi A, and Galimberti D more...
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- Humans, Female, Male, Middle Aged, Aged, C9orf72 Protein genetics, Chemokines blood, Chemokines genetics, Cohort Studies, Intercellular Signaling Peptides and Proteins genetics, Intercellular Signaling Peptides and Proteins blood, Heterozygote, Frontotemporal Dementia genetics, Frontotemporal Dementia blood, Progranulins genetics, Progranulins blood, Cytokines blood, Cytokines genetics, tau Proteins blood, tau Proteins genetics, Inflammation genetics, Inflammation blood, Mutation
- Abstract
Background: Inflammation has been proposed as a crucial player in neurodegeneration, including Frontotemporal Dementia (FTD). A few studies on sporadic FTD lead to inconclusive results, whereas large studies on genetic FTD are lacking. The aim of this study is to determine cytokine and chemokine plasma circulating levels in a large cohort of genetic FTD, collected within the GENetic Frontotemporal dementia Initiative (GENFI)., Methods: Mesoscale technology was used to analyse levels of 30 inflammatory factors in 434 plasma samples, including 94 Symptomatic Mutation carriers [(SMC); 15 with mutations in Microtubule Associated Protein Tau (MAPT) 34 in Progranulin (GRN) and 45 in Chromosome 9 Open Reading Frame (C9ORF)72], 168 Presymptomatic Mutation Carriers (PMC; 34 MAPT, 70 GRN and 64 C9ORF72) and 173 Non-carrier Controls (NC)]., Results: The following cytokines were significantly upregulated (P<0.05) in MAPT and GRN SMC versus NC: Tumor Necrosis Factor (TNF)α, Interleukin (IL)-7, IL-15, IL-16, IL-17A. Moreover, only in GRN SMC, additional factors were upregulated, including: IL-1β, IL-6, IL-10, IL-12/IL-23p40, eotaxin, eotaxin-3, Interferon γ-induced Protein (IP-10), Monocyte Chemotactic Protein (MCP)4. On the contrary, IL-1α levels were decreased in SMC compared with NC. Significantly decreased levels of this cytokine were also found in PMC, independent of the type of mutation. In SMC, no correlations between disease duration and cytokine and chemokine levels were found. Considering NfL and GFAP levels, as expected, significant increases were observed in SMC as compared to NC. These differences in mean values remain significant even when stratifying symptomatic patients by the mutated gene (P<0.0001). Considering instead the levels of NfL, GFAP, and the altered inflammatory molecules, no significant correlations emerged., Conclusion: We showed that inflammatory proteins are upregulated in MAPT and GRN SMC, with some specific factors altered in GRN only, whereas no changes were seen in C9ORF72 carriers. Notably, only IL-1α levels were decreased in both SMC and PMC, independent of the type of causal mutation, suggesting common modifications occurring in the preclinical phase of the disease., 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 © 2024 Elsevier Inc. All rights reserved.) more...
- Published
- 2024
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7. Learning curve in retroperitoneal sarcoma surgery.
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Samà L, Kumar S, Ruspi L, Sicoli F, D'Amato V, Mintemur Ö, Renne SL, Quagliuolo VL, and Cananzi FC
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- Humans, Male, Retrospective Studies, Middle Aged, Female, Aged, Adult, Clinical Competence, Retroperitoneal Neoplasms surgery, Retroperitoneal Neoplasms pathology, Sarcoma surgery, Learning Curve, Operative Time
- Abstract
Introduction: Retroperitoneal sarcoma (RPS) surgery poses unique challenges. This retrospective study aimed to analyze the learning curve (LC) in RPS surgery, assessing the relationship between surgical experience and outcomes., Materials and Methods: Cumulative sum (CUSUM) analysis was used to analyze 62 RPS surgeries performed by a single surgeon between 2016 and 2022 at our center., Results: The number of cases where the surgeon acted as first operator increased from 3 in 2016 to 13 in 2022. The surgeon operated with his mentor in 66.7 % of cases in 2016, whereas in 7.7 % of cases in 2022. LC consisted of 3 phases. Phase 1 (16 cases), with a negative slope, represented shorter operative time (OT) and fewer number of resected organs (RO). Phase 2 (30 cases) was the plateau phase. Phase 3 (16 cases), with a positive slope, indicated longer OT and more RO. Statistically significant differences were observed in terms of size (p = 0.003), presentation (p = 0.048), number of resected organs (p = 0.046), pattern of resection (p = 0.033), OT (p = 0.006), and length of stay (p = 0.026) between the three phases., Conclusion: This study focused on the critical role of LC in RPS surgery, emphasizing its influence on outcomes. We identified three phases, highlighting the surgeon's evolution. This offers a framework for educating sarcoma surgeons and ensuring exposure to increasing surgical complexity. In discussions on sarcoma referral centers and the correlation between case volume and outcomes, this study underlines the importance of evaluating LC to distinguish surgeons qualified to manage sarcoma cases within a referral center., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Ltd.) more...
- Published
- 2024
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8. Excessive alcohol intake produces persistent mechanical allodynia and dysregulates the endocannabinoid system in the lumbar dorsal root ganglia of genetically-selected Marchigian Sardinian alcohol-preferring rats.
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Borgonetti V, Vozella V, Ware T, Cruz B, Bullard R, Cravatt BF, Galeotti N, and Roberto M
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- Animals, Male, Female, Alcohol Drinking adverse effects, Rats, Ethanol, Glycerides metabolism, Arachidonic Acids metabolism, Alcoholism metabolism, Alcoholism complications, Endocannabinoids metabolism, Hyperalgesia metabolism, Rats, Wistar, Ganglia, Spinal metabolism, Ganglia, Spinal drug effects
- Abstract
Epidemiological data indicate a strong association between alcohol use disorder (AUD) and neuropathic pain. Genetically-selected Marchigian Sardinian alcohol-preferring (msP) rats exhibit a high preference for alcohol compared with their background strain (Wistar rats), but their sensitivity to mechanical allodynia after chronic alcohol exposure is unknown. The present study compared the development of mechanical allodynia between "low, non-pathological drinker" Wistar rats and "high drinker" msP rats using the two-bottle choice (2BC) free-access procedure. Several studies reported the involvement of endocannabinoids (eCBs) in modulating mechanical allodynia, but there are no data on their role in alcohol-related allodynia. Thus, the present study assessed eCBs and their related lipid species in lumbar dorsal root ganglia (DRG) and correlated them with mechanical allodynia in our model. We found that male and female msP rats developed persistent mechanical allodynia during protracted abstinence from alcohol, presenting no sign of recovery, as opposed to Wistar rats. This effect directly correlated with their total alcohol intake. Notably, we found a correlation between lower lumbar DRG 2-arachidonoylglycerol (2-AG) levels and the development of higher mechanical allodynia during abstinence in msP rats of both sexes but not in Wistar rats. Moreover, alcohol-exposed and abstinent msP and Wistar females but not males exhibited significant alterations of thromboxane B2 and prostaglandin E2/prostaglandin D2 compared with naive rats. These findings demonstrate that DRG 2-AG metabolism is altered in msP rats during prolonged abstinence and represents a potentially interesting pharmacological target for the treatment of mechanical allodynia during alcohol abstinence., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2024
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9. Methyltransferases in cancer drug resistance: Unlocking the potential of targeting SMYD3 to sensitize cancer cells.
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Sanese P, Fasano C, Lepore Signorile M, De Marco K, Forte G, Disciglio V, Grossi V, and Simone C
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- Humans, DNA Repair drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Animals, DNA Damage drug effects, Protein Processing, Post-Translational, Drug Resistance, Neoplasm, Histone-Lysine N-Methyltransferase metabolism, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase antagonists & inhibitors, Neoplasms drug therapy, Neoplasms genetics, Neoplasms pathology
- Abstract
Drug resistance is a significant challenge in oncology and is driven by various mechanisms, among which a crucial role is played by enhanced DNA repair. Thus, targeting DNA damage response (DDR) factors with specific inhibitors is emerging as a promising therapeutic strategy. An important process involved in the modulation of DNA repair pathways, and hence in drug resistance, is post-translational modification (PTM). PTMs such as methylation affect protein function and are critical in cancer biology. Methylation is catalyzed by specific enzymes called protein methyltransferases. In recent years, the SET domain-containing N-lysine methyltransferase SMYD3 has emerged as a significant oncogenic driver. It is overexpressed in several tumor types and plays a signal-dependent role in promoting gastrointestinal cancer formation and development. Recent evidence indicates that SMYD3 is involved in the maintenance of cancer genome integrity and contributes to drug resistance in response to genotoxic stress by regulating DDR mechanisms. Several potential SMYD3 interactors implicated in DNA repair, especially in the homologous recombination and non-homologous end-joining pathways, have been identified by in silico analyses and confirmed by experimental validation, showing that SMYD3 promotes DDR protein interactions and enzymatic activity, thereby sustaining cancer cell survival. Targeting SMYD3, in combination with standard or targeted therapy, shows promise in overcoming drug resistance in colorectal, gastric, pancreatic, breast, endometrial, and lung cancer models, supporting the integration of SMYD3 inhibition into cancer treatment regimens. In this review, we describe the role played by SMYD3 in drug resistance and analyze its potential as a molecular target to sensitize cancer cells to treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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10. Risk of venous thromboembolism and arterial events in patients with hypoalbuminemia: a comprehensive meta-analysis of more than 2 million patients.
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Valeriani E, Pannunzio A, Palumbo IM, Bartimoccia S, Cammisotto V, Castellani V, Porfidia A, Pignatelli P, and Violi F
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- Humans, Biomarkers blood, Myocardial Infarction blood, Myocardial Infarction epidemiology, Risk Assessment, Risk Factors, Stroke blood, Stroke epidemiology, Hypoalbuminemia blood, Hypoalbuminemia complications, Venous Thromboembolism blood, Venous Thromboembolism epidemiology, Venous Thromboembolism diagnosis, Venous Thromboembolism etiology
- Abstract
Background: Albumin has antiplatelet and anticoagulant functions. Hypoalbuminemia, as defined by serum values of <3.5 g/dL, is associated with arterial thrombosis; its impact on venous thromboembolism (VTE) is unclear., Objectives: The objective of this meta-analysis is to assess the VTE risk in patients with hypoalbuminemia., Methods: MEDLINE and EMBASE were searched up to January 2024 for observational studies and randomized trials reporting data of interest. Primary outcome was the risk of VTE, while secondary outcomes were myocardial infarction and stroke risk in patients with hypoalbuminemia versus those without hypoalbuminemia. The risk of bias was evaluated using Newcastle-Ottawa scale and Cochrane tool. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model., Results: Forty-three studies for a total of 2 531 091 patients (39 738 medical and 2 491 353 surgical) were included in primary analysis; 79.1% of the studies used 3.5 g/dL cut-off value for hypoalbuminemia definition. Follow-up duration was 30 days in 60.5% of studies. Patients with hypoalbuminemia had a higher risk of VTE (RR, 1.88; 95% CI, 1.66-2.13). RRs were similar in both medical (RR, 1.87; 95% CI, 1.53-2.27) and surgical patients (RR, 1.87; 95% CI, 1.61-2.16) and in patients with (RR, 1.86; 95% CI, 1.66-2.10) and without cancer (RR, 1.89; 95% CI, 1.47-2.44). Risk of myocardial infarction (RR, 1.88; 95% CI, 1.54-2.31) and stroke (RR, 1.77; 95% CI, 1.26-2.48) was higher in patients with hypoalbuminemia., Conclusion: Hypoalbuminemia is a risk factor for VTE in both medical and surgical patients irrespective of cancer coexistence. Serum albumin analysis may represent a simple and cheap tool to identify patients at VTE risk., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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11. ERK5 mediates pro-tumorigenic phenotype in non-small lung cancer cells induced by PGE2.
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Filippelli A, Ciccone V, Del Gaudio C, Simonis V, Frosini M, Tusa I, Menconi A, Rovida E, and Donnini S
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- Humans, A549 Cells, Cell Line, Tumor, Carcinogenesis genetics, Carcinogenesis metabolism, Phenotype, Dinoprostone metabolism, Dinoprostone pharmacology, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung genetics, Mitogen-Activated Protein Kinase 7 metabolism, Mitogen-Activated Protein Kinase 7 genetics, Lung Neoplasms pathology, Lung Neoplasms metabolism, Lung Neoplasms genetics, Cell Proliferation, Cell Movement drug effects
- Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting approximately 84 % of all lung cancer cases. The role of inflammation in the initiation and progression of NSCLC tumors has been the focus of extensive research. Among the various inflammatory mediators, prostaglandin E2 (PGE2) plays a pivotal role in promoting the aggressiveness of epithelial tumors through multiple mechanisms, including the stimulation of growth, evasion of apoptosis, invasion, and induction of angiogenesis. The Extracellular signal-Regulated Kinase 5 (ERK5), the last discovered member among conventional mitogen-activated protein kinases (MAPK), is implicated in cancer-associated inflammation. In this study, we explored whether ERK5 is involved in the process of tumorigenesis induced by PGE2. Using A549 and PC9 NSCLC cell lines, we found that PGE2 triggers the activation of ERK5 via the EP1 receptor. Moreover, both genetic and pharmacological inhibition of ERK5 reduced PGE2-induced proliferation, migration, invasion and stemness of A549 and PC9 cells, indicating that ERK5 plays a critical role in PGE2-induced tumorigenesis. In summary, our study underscores the pivotal role of the PGE2/EP1/ERK5 axis in driving the malignancy of NSCLC cells in vitro. Targeting this axis holds promise as a potential avenue for developing novel therapeutic strategies aimed at controlling the advancement of NSCLC., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2024
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12. Effectiveness of gellan gum scaffolds loaded with Boswellia serrata extract for in-situ modulation of pro-inflammatory pathways affecting cartilage healing.
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Cometa S, Busto F, Scalia AC, Castellaneta A, Gentile P, Cochis A, Manfredi M, Borrini V, Rimondini L, and De Giglio E
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- Tissue Scaffolds chemistry, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells metabolism, Humans, Wound Healing drug effects, Hydrogels chemistry, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents chemistry, Inflammation drug therapy, Inflammation pathology, Triterpenes, Boswellia chemistry, Polysaccharides, Bacterial chemistry, Polysaccharides, Bacterial pharmacology, Plant Extracts pharmacology, Plant Extracts chemistry, Chondrogenesis drug effects, Cartilage drug effects, Cartilage metabolism
- Abstract
In this study, we developed a composite hydrogel based on Gellan gum containing Boswellia serrata extract (BSE). BSE was either incorporated directly or loaded into an MgAl-layered double hydroxide (LDH) clay to create a multifunctional cartilage substitute. This composite was designed to provide anti-inflammatory properties while enhancing chondrogenesis. Additionally, LDH was exploited to facilitate the loading of hydrophobic BSE components and to improve the hydrogel's mechanical properties. A calcination process was also adopted on LDH to increase BSE loading. Physicochemical and mechanical characterizations were performed by spectroscopic (XPS and FTIR), thermogravimetric, rheological, compression test, weight loss and morphological (SEM) investigations. RPLC-ESI-FTMS was employed to investigate the boswellic acids release in simulated synovial fluid. The composites were cytocompatible and capable of supporting the mesenchymal stem cells (hMSC) growth in a 3D-conformation. Loading BSE resulted in the modulation of the pro-inflammatory cascade by down-regulating COX2, PGE2 and IL1β. Chondrogenesis studies demonstrated an enhanced differentiation, leading to the up-regulation of COL 2 and ACAN. This effect was attributed to the efficacy of BSE in reducing the inflammation through PGE2 down-regulation and IL10 up-regulation. Proteomics studies confirmed gene expression findings by revealing an anti-inflammatory protein signature during chondrogenesis of the cells cultivated onto loaded specimens. Concluding, BSE-loaded composites hold promise as a tool for the in-situ modulation of the inflammatory cascade while preserving cartilage healing., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2024
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13. SARS-CoV-2 uses Spike glycoprotein to control the host's anaerobic metabolism by inhibiting LDHB.
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Monaco V, Iacobucci I, Canè L, Cipollone I, Ferrucci V, de Antonellis P, Quaranta M, Pascarella S, Zollo M, and Monti M
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- Humans, HEK293 Cells, Isoenzymes metabolism, Anaerobiosis, Angiotensin-Converting Enzyme 2 metabolism, NAD metabolism, Protein Binding, Spike Glycoprotein, Coronavirus metabolism, Spike Glycoprotein, Coronavirus chemistry, SARS-CoV-2 metabolism, L-Lactate Dehydrogenase metabolism, COVID-19 metabolism, COVID-19 virology
- Abstract
The SARS-CoV-2 pandemic, responsible for approximately 7 million deaths worldwide, highlights the urgent need to understand the molecular mechanisms of the virus in order to prevent future outbreaks. The Spike glycoprotein of SARS-CoV-2, which is critical for viral entry through its interaction with ACE2 and other host cell receptors, has been a focus of this study. The present research goes beyond receptor recognition to explore Spike's influence on cellular metabolism. AP-MS interactome analysis revealed an interaction between the Spike S1 domain and lactate dehydrogenase B (LDHB), which was further confirmed by co-immunoprecipitation and immunofluorescence, indicating colocalisation in cells expressing the S1 domain. The study showed that Spike inhibits the catalytic activity of LDHB, leading to increased lactate levels in HEK-293T cells overexpressing the S1 subunit. In the hypothesised mechanism, Spike deprives LDHB of NAD
+ , facilitating a metabolic switch from aerobic to anaerobic energy production during infection. The Spike-NAD+ interacting region was characterised and mainly involves the W436 within the RDB domain. This novel hypothesis suggests that the Spike protein may play a broader role in altering host cell metabolism, thereby contributing to the pathophysiology of viral infection., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...- Published
- 2024
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14. Specific locations of myocardial inflammation and fibrosis are associated with higher risk of events in cardiac sarcoidosis.
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Devesa A, Robson PM, Cangut B, Vazirani R, Vergani V, LaRocca G, Romero-Daza AM, Liao S, Azoulay LD, Pyzik R, Fayad RA, Jacobi A, Abgral R, Morgenthau AS, Miller MA, Fayad ZA, and Trivieri MG
- Abstract
Background:
18 F-Fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/magnetic resonance (MR) can identify inflammation and fibrosis, which are high-risk features in cardiac sarcoidosis., Objective: The purpose of this study was to evaluate whether the involvement of certain myocardial segments is associated with higher risk compared to others., Methods: One hundred twenty-four patients with suspected clinical sarcoidosis underwent18 F-FDG-PET/MR. Late gadolinium enhancement (LGE) and focal18 F-FDG uptake were evaluated globally and in the 16 myocardial segments. Presence of LGE was defined when the percentage of LGE exceeded 5.7% globally (relative to myocardial volume) and in each myocardial segment. Patients were followed up for 5.5 years. Events were defined as ventricular arrhythmia (VA) (including sustained ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter-defibrillator discharge), heart failure hospitalization, or all-cause death., Results: Mean age was 57.1 ± 8.9 years, and 39.5% were female. Twenty-two patients (17.6%) had an event during follow-up, and 9 (7.2%) presented with VA. LGE and18 F-FDG uptake were more frequent in patients with than without events (36.4% vs 7.8%, P = .001). Presence of LGE and18 F-FDG in the basal anterior segment were independent predictors for events after adjustment for left ventricular ejection fraction and relative enhanced volume (LGE: odds ratio [1.2-92.4], P = .034;18 F-FDG: odds ratio 5.5 [1.1-27.5], P = .038). LGE presence in basal to mid-anterior, mid-anteroseptal, and basal to mid-inferoseptal segments was an independent predictor of VA. Presence of18 F-FDG in basal to mid-anterior, mid-inferoseptal and mid-inferior segments was an independent predictor of VA., Conclusion: Involvement of specific myocardial segments, particularly basal to mid-anterior and mid-septal segments, is associated with higher rates of events in patients with suspected cardiac sarcoidosis., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2024
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15. Clinical characteristics, treatment, trajectories and outcome of patients with dilated cardiomyopathy in a national heart failure registry.
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Carigi S, Gentile P, Gori M, Tinti D, De Gennaro L, Leonardi G, Orso F, Felici AR, Catalano MR, Floresta M, Rizzello V, Lucci D, Gonzini L, De Maria R, and Marini M
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Treatment Outcome, Follow-Up Studies, Registries, Cardiomyopathy, Dilated physiopathology, Cardiomyopathy, Dilated drug therapy, Cardiomyopathy, Dilated epidemiology, Heart Failure drug therapy, Heart Failure physiopathology, Heart Failure epidemiology, Heart Failure diagnosis
- Abstract
Background: Available data on the clinical characteristics and prognosis of patients with heart failure (HF) due to dilated cardiomyopathy (DCM) derive mainly from tertiary care centres for cardiomyopathies or from drug trial sub-studies, which may entail a referral bias., Methods: From 2008 to 2021, we enrolled in a nationwide HF Registry 1886 DCM patients and 3899 with ischemic heart disease (IHD)., Results: Patients with DCM were younger, more often female, had more commonly recent onset HF, left bundle branch block, and showed higher LV end-diastolic volume and lower LVEF than IHD. With respect to IHD, DCM patients received more often mineralocorticoid receptor antagonists, renin angiotensin system inhibitors and betablockers, the latter more commonly at doses ≥50% of target, and triple guideline-directed medical therapy (GDMT) (adjusted OR 1.411, 95% CI 1.247-1.595, p < .0001). During one-year follow-up, 819 patients (14.2%) died or were hospitalized for HF [187 (9.9%) DCM, 632 (16.2%) IHD]; DCM was associated with lower risk of the combined end-point (adjusted HR 0.745, 95% CI 0.625- 0.888, p = .0011). Among the 1954 patients with 1-year echocardiograms available, 1483 had LVEF≤40% at baseline; of these,166 (30.6%) DCM and 165 (17.5%) IHD improved their LVEF to >40% (p < .0001). DCM aetiology was associated with higher likelihood of LVEF improvement (adjusted OR 1.722, 95% CI 1.328 -2.233, p < .0001)., Conclusions: DCM patients have a different clinical profile, greater uptake of GDMT and better outcomes than IHD subjects. A comprehensive management approach is needed to further address the risk of unfavorable outcomes in DCM., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...
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- 2024
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16. Perampanel in post-stroke epilepsy: Clinical practice data from the PERampanel as Only Concomitant antiseizure medication (PEROC) study.
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Pascarella A, Manzo L, Gasparini S, Marsico O, Abelardo D, Torino C, Cianci V, Iudice A, Bisulli F, Bonanni P, Caggia E, D'Aniello A, Di Bonaventura C, DiFrancesco JC, Domina E, Dono F, Gambardella A, Fortunato F, Marini C, Marrelli A, Matricardi S, Morano A, Paladin F, Renna R, Piccioli M, Striano P, Ascoli M, La Neve A, Le Piane E, Orsini A, Di Gennaro G, Aguglia U, and Ferlazzo E more...
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- Humans, Female, Male, Aged, Middle Aged, Retrospective Studies, Longitudinal Studies, Treatment Outcome, Drug Therapy, Combination, Aged, 80 and over, Adult, Pyridones therapeutic use, Pyridones adverse effects, Nitriles, Anticonvulsants therapeutic use, Epilepsy drug therapy, Stroke complications, Stroke drug therapy
- Abstract
Introduction: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy. Nevertheless, there is limited evidence regarding the clinical profile of antiseizure medications (ASMs) in PSE. This study aims to evaluate the 12-month effectiveness and tolerability of perampanel (PER) used as only add-on treatment in patients with PSE in a real-world setting., Methods: We performed a subgroup analysis of PSE patients included in a previous retrospective, longitudinal, multicentre observational study on adults. Treatment discontinuation, seizure frequency and adverse events were collected at 3, 6 and 12 months. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted., Results: Our analysis included 56 individuals with PSE, characterized by varying initial treatment modalities and timeframes relative to disease onset. We found notable retention rates (92.8%, 83.7%, and 69% at 3, 6, and 12 months), with treatment withdrawal mainly due to poor tolerability. One year after PER introduction, seizure frequency significantly reduced, with a responder rate (≥50% reduction) of 83.9% and a seizure-free rate of 51.6%. Adverse events occurred in 25 (46.3%) patients, mainly dizziness, irritability, and behavioural disorders. No major statistical differences were found between early (30 patients, 53.6%) and late add-on groups, except for a higher 6-month responder rate in the early add-on group., Conclusion: Adjunctive PER was effective and well-tolerated in patients with PSE in a real-world setting. Perampanel demonstrated good efficacy and safety as both early and late add-on treatment, making it a compelling option for this unique patient population., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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17. Warm-up plus verbal communications administered as placebo procedure during the training session improves running performance.
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Bisio A, Panascì M, Ferrando V, Albergoni A, Ruggeri P, and Faelli E
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- Humans, Male, Young Adult, Female, Adult, Communication, High-Intensity Interval Training methods, Placebo Effect, Running physiology, Athletic Performance physiology, Warm-Up Exercise
- Abstract
The aim of this study was to investigate the effects on running performance of a within-session placebo procedure consisting of a conditioning treatment plus verbal communications. Twenty-six subjects were assigned to PLACEBO and CONTROL groups. Participants performed three sessions: Session 1-Cooper Test, Session 2-Baseline session and Session 3-Experimental session. During Session 2, participants performed a sprint-interval-training (SIT)-until-exhaustion preceded by a general warm-up, while in Session3 the SIT was preceded by a conditioning treatment (FIFA11+ warm-up), known to be effective in preventing injuries but not improving performance. Moreover, in Session3, only the PLACEBO group received verbal suggestions (before the warm-up) to influence participants' expectations about FIFA11+ effectiveness in improving performance, and deceptive feedback (during each SIT recovery bout) to increase the conditioning effect. To evaluate performance improvements, Running Time was chosen as a main outcome while to ensure participants reached exhaustion, physiological and metabolic responses were monitored. Total running distance (TRD) was also measured. Results showed that, Running Time and TRD significantly increased in the PLACEBO group whilst no differences in the CONTROL group were observed thus, suggesting the effectiveness of the within-session-placebo procedure in improving running performance. These findings shed a new light on the interaction between cognitive domain and performance, thus encouraging coaches to adopt this innovative method during the training protocol to enhance athletes' performance. Moreover, this placebo procedure, not requiring additional time, tools or resources, could represent a more ecological approach that can be easily adopted in the field., Competing Interests: Declaration of competing interest The authors on this manuscript have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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18. Daily instability in body dissatisfaction in individuals with and without eating disorders.
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Zhu LY, Trolio V, Miller AE, Bicaker E, and Racine SE
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- Humans, Female, Adult, Young Adult, Male, Exercise psychology, Ecological Momentary Assessment, Adolescent, Body Image psychology, Self Report, Personal Satisfaction, Feeding and Eating Disorders psychology, Body Dissatisfaction psychology
- Abstract
Body dissatisfaction (BD) includes negative thoughts and feelings about one's body shape. Although typically assessed as a trait, BD has been found to fluctuate within a day. The present study examined whether daily instability in BD differs according to trait BD, eating disorder (ED) diagnosis, and engagement in maladaptive exercise. Participants with EDs (n = 166) and controls (n = 44) completed a self-report measure of trait BD and reported BD and engagement in maladaptive exercise five times daily for 14 days as part of an ecological momentary assessment protocol. BD instability was calculated as adjusted mean squared successive difference. On average across assessments, participants with EDs reported a 16% change in their BD ratings between consecutive assessments, which was significantly higher than the 12% change in controls. Trait BD was significantly inversely associated with BD instability in individuals with EDs, but not in controls. BD instability did not differ across ED diagnoses or between days with versus without maladaptive exercise. Findings suggest that BD is a dynamic state that varies within a day, especially in participants with EDs. Further research is needed to clarify whether this heightened instability in BD is a clinically relevant factor underlying ED symptoms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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19. Organelle adaptations in response to mechanical forces during tumour dissemination.
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Graziani V, Crosas-Molist E, George SL, and Sanz-Moreno V
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- Animals, Humans, Cell Movement, Mechanotransduction, Cellular, Mitochondria metabolism, Neoplasm Metastasis, Extracellular Matrix metabolism, Neoplasms pathology, Neoplasms metabolism, Organelles metabolism
- Abstract
Cell migration plays a pivotal role in various biological processes including cancer dissemination and successful metastasis, where the role of mechanical signals is increasingly acknowledged. This review focuses on the intricate mechanisms through which cancer cells modulate their migratory strategies via organelle adaptations in response to the extracellular matrix (ECM). Specifically, the nucleus and mitochondria emerge as pivotal mediators in this process. These organelles serve as sensors, translating mechanical stimuli into rapid metabolic alterations that sustain cell migration. Importantly, prolonged exposure to such stimuli can induce transcriptional or epigenetic changes, ultimately enhancing metastatic traits. Deciphering the intricate interplay between ECM properties and organelle adaptations not only advances our understanding of cytoskeletal dynamics but also holds promise for the development of innovative anti-metastatic therapeutic strategies., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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20. Study protocol for two stepped-wedge interventional trials evaluating the effects of holistic information technology-based patient-oriented management in older multimorbid patients with cancer: The GERONTE trials.
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Hamaker ME, Wildiers H, Ardito V, Arsandaux J, Barthod-Malat A, Davies P, Degol L, Ferrara L, Fourrier C, Kenis C, Kret M, Lalet C, Pelissier SM, O'Hanlon S, Rostoft S, Seghers N, Saillour-Glénisson F, Staines A, Schwimmer C, Thevenet V, Wallet C, and Soubeyran P more...
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- Humans, Aged, Information Technology, Critical Pathways, Holistic Health, Aged, 80 and over, Male, Female, Neoplasms complications, Neoplasms therapy, Multimorbidity, Patient-Centered Care
- Abstract
Introduction: Current hospital-based care pathways are generally single-disease centred. As a result, coexisting morbidities are often suboptimally evaluated and managed, a deficiency becoming increasingly apparent among older patients who exhibit heterogeneity in health status, functional abilities, frailty, and other geriatric impairments. To address this issue, our study aims to assess a newly developed patient-centred care pathway for older patients with multimorbidity and cancer. The new care pathway was based on currently available evidence and co-designed by end-users including health care professionals, patients, and informal caregivers. Within this care pathway, all healthcare professionals involved in the care of older patients with multimorbidity and cancer will form a Health Professional Consortium (HPC). The role of the HPC will be to centralise oncologic and non-oncologic treatment recommendations in accordance with the patient's priorities. Moreover, an Advanced Practice Nurse will act as case-manager by being the primary point of contact for the patient, thus improving coordination between specialists, and by organising and leading the consortium. Patient monitoring and the HPC collaboration will be facilitated by digital communication tools designed specifically for this purpose, with the added benefit of being customisable for each patient., Materials and Methods: The GERONTE study is a prospective international, multicentric study consisting of two stepped-wedge trials performed at 16 clinical sites across three European countries. Each trial will include 720 patients aged 70 years and over with a new or progressive cancer (breast, lung, colorectal, prostate) and at least one moderate or severe multimorbidity. The patients in the intervention group will receive the new care pathway whereas patients in the control group will receive usual oncologic care., Discussion: GERONTE will evaluate whether this kind of holistic, patient-oriented healthcare management can improve quality of life (primary outcome) and other valuable endpoints in older patients with multimorbidity and cancer. An ancillary study will assess in depth the socio-economic impact of the intervention and deliver concrete implementation guidelines for the GERONTE intervention care pathway., Trial Registration: FRONE: NCT05720910 TWOBE: NCT05423808., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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21. Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis.
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Trivieri MG, Robson PM, Vergani V, LaRocca G, Romero-Daza AM, Abgral R, Devesa A, Azoulay LD, Karakatsanis NA, Parikh A, Panagiota C, Palmisano A, DePalo L, Chang HL, Rothstein JH, Fayad RA, Miller MA, Fuster V, Narula J, Dweck MR, Morgenthau A, Jacobi A, Padilla M, Kovacic JC, and Fayad ZA more...
- Subjects
- Humans, Fluorodeoxyglucose F18, Contrast Media, Radiopharmaceuticals, Predictive Value of Tests, Gadolinium, Positron-Emission Tomography methods, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy, Cardiomyopathies diagnostic imaging, Cardiomyopathies therapy, Cardiomyopathies complications, Myocarditis complications, Sarcoidosis diagnostic imaging, Sarcoidosis therapy, Sarcoidosis complications
- Abstract
Background: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and
18 F-fluorodeoxyglucose (18 F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+)., Objectives: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes., Methods: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of18 F-FDG (PET+/PET-), and pattern of18 F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL , MR(+)PET(+)DIFFUSE , MR(+)PET(-), MR(-)PET(+)FOCAL , MR(-)PET(+)DIFFUSE , MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-)5.7% . Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints., Results: Patients designated MR(+)5.7% PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL , and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint., Conclusions: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health (NIH) grant R01 HL071021 (ZAF), NIH grant KL2 TR001435 (MGT), and AHA grant 20CDA35310099 (MGT). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.) more...- Published
- 2024
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22. Survival associated with the use of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node metastasis in cervical cancer.
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Bizzarri N, Fedele C, Teodorico E, Certelli C, Pedone Anchora L, Carbone V, Giannarelli D, Fagotti A, Zannoni GF, Valente M, Querleu D, Ferrandina G, Scambia G, and Fanfani F
- Subjects
- Female, Humans, Lymphatic Metastasis pathology, Cohort Studies, Retrospective Studies, Sentinel Lymph Node Biopsy methods, Lymph Nodes pathology, Lymph Node Excision, Nucleic Acid Amplification Techniques methods, Sentinel Lymph Node pathology, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms surgery, Uterine Cervical Neoplasms pathology, Lymphadenopathy pathology, Nucleic Acids
- Abstract
Introduction: Sentinel lymph node (SLN) biopsy is part of surgical treatment of apparent early-stage cervical cancer. SLN is routinely analyzed by ultrastaging and immunohistochemistry. The aim of this study was to assess the survival of patients undergoing SLN analyzed by one-step nucleic acid amplification (OSNA) compared with ultrastaging., Methods: Single-center, retrospective, cohort study. Patients undergoing primary surgery and SLN mapping ( ±pelvic lymphadenectomy) for apparent early-stage cervical cancer between May 2017 and January 2021 were included. SLN was analyzed exclusively with OSNA or with ultrastaging. Patients with bilateral SLN mapping failure, with SLN analyzed alternatively/serially with OSNA and ultrastaging, and undergoing neo-adjuvant therapy were excluded. Baseline clinic-pathological differences between the two groups were balanced with propensity-match analysis., Results: One-hundred and fifty-seven patients were included, 50 (31.8%) in the OSNA group and 107 (68.2%) in the ultrastaging group. Median follow up time was 41 months (95%CI:37.9-42.2). 5-year DFS in patients undergoing OSNA versus ultrastaging was 87.0% versus 91.0% (p = 0.809) and 5-year overall survival was 97.9% versus 98.6% (p = 0.631), respectively. No difference in the incidence of lymph node recurrence between the two groups was noted (OSNA 20.0% versus ultrastaging 18.2%, p = 0.931). In the group of negative SLN, no 5-year DFS difference was noted between the two groups (p = 0.692). No 5-year DFS and OS difference was noted after propensity-match analysis (87.6% versus 87.0%, p = 0.726 and 97.4% versus 97.9%, p = 0.998, respectively)., Conclusion: The use of OSNA as method to exclusively process SLN in cervical cancer was not associated with worse DFS compared to ultrastaging. Incidence of lymph node recurrence in the two groups was not different., Competing Interests: Declaration of competing interest None., (© 2024 Published by Elsevier Ltd.) more...
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- 2024
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23. Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.
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Romani I, Sarti C, Nencini P, Pracucci G, Zedde M, Cianci V, Nucera A, Moller J, Orsucci D, Toni D, Palumbo P, Casella C, Pinto V, Barbarini L, Bella R, Scoditti U, Ragno M, Mezzapesa DM, Tassi R, Volpi G, Diomedi M, Bigliardi G, Cavallini AM, Chiti A, Ricci S, Cecconi E, Linoli G, Sacco S, Rasura M, Giordano A, Bonetti B, Melis M, Cariddi LP, Dossi RC, Grisendi I, Aguglia U, Di Ruzza MR, Melis M, Sbardella E, Vista M, Valenti R, Musolino RF, Passarella B, Direnzo V, Pennisi G, Genovese A, Di Marzio F, Sgobio R, Acampa M, Nannucci S, Dagostino F, Dell'Acqua ML, Cuzzoni MG, Picchioni A, Calchetti B, Notturno F, Di Lisi F, Forlivesi S, Delodovici ML, Buechner SC, Biagini S, Accavone D, Manna R, Morrone A, and Inzitari D more...
- Subjects
- Female, Humans, Male, Italy epidemiology, Mutation, Prevalence, Prospective Studies, Adolescent, Young Adult, Adult, Middle Aged, alpha-Galactosidase genetics, Fabry Disease diagnosis, Fabry Disease epidemiology, Fabry Disease genetics, Ischemic Attack, Transient diagnosis, Ischemic Attack, Transient epidemiology, Ischemic Stroke diagnosis, Ischemic Stroke epidemiology, Ischemic Stroke genetics
- Abstract
Background: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes)., Methods: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present., Results: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant., Conclusion: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening., Competing Interests: Declaration of competing interest IR received travel grants and speaker's honoraria from Takeda, Sanofi, and Amicus; PN received speaker's honoraria from Takeda, Sanofi, and Amicus; MZ received fees as consultant and advisory board member from Takeda, Sanofi, and Amicus; SS received personal fees as speaker or advisor (Abbott, Allergan-Abbvie, AstraZeneca, Eli Lilly, Lundbeck, Novartis, NovoNordisk, Pfizer, Teva), research grants (Allergan, Novartis, Uriach), and fees for CME/education (Medscape, Neurodiem Ology Medical Education); UA received speaker's fees and honoraria from EISAI; AM received speaker's honoraria and travel grants from Takeda, Sanofi, and Amicus; DI received speaker's honoraria from Takeda. Other authors declared that they have no competing interests for FSIR study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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24. A proteomic approach to investigate the role of the MECP2 gene mutation in Rett syndrome redox regulatory pathways.
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Pasqui A, Cicaloni V, Tinti L, Guiotto A, Tinti C, Mori A, Bruttini M, Hayek J, Pecorelli A, Salvini L, and Valacchi G
- Subjects
- Humans, Hydrogen Peroxide, Methyl-CpG-Binding Protein 2 genetics, Mutation, Oxidation-Reduction, Phenotype, Proteins, Proteomics, Rett Syndrome genetics
- Abstract
Mutations in the X-linked methyl-CpG-binding 2 (MECP2) gene lead to Rett Syndrome (RTT; OMIM 312750), a devasting neurodevelopmental disorder. RTT clinical manifestations are complex and with different degrees of severity, going from autistic-like behavior to loss of acquired speech, motor skills and cardiac problems. Furthermore, the correlation between the type of MECP2 mutation and the clinical phenotype is still not fully understood. Contextually, different genotypes can differently affect the patient's phenotype and omics methodologies such as proteomics could be an important tool for a molecular characterization of genotype/phenotype correlation. The aim of our study was focused on evaluating RTT oxidative stress (OS) responses related to specific MECP2 gene mutations by using proteomics and bioinformatics approaches. Primary fibroblasts isolated from patients affected by R133C and R255× mutations were compared to healthy controls (HC). After clustering primary dermal fibroblasts based on their specific MECP2 mutations, fibroblast-derived protein samples were qualitative and quantitative analyzed, using a label free quantification (LFQ) analysis by mass spectrometry (MS), achieving a preliminary correlation for RTT genotype/phenotype. Among the identified proteins involved in redox regulation pathways, NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) was found to be absent in R255× cells, while it was present in R133C and in HC fibroblasts. Moreover, NQO1 aberrant gene regulation was also confirmed when cells were challenged with 100 μM hydrogen peroxide (H
2 O2 ). In conclusion, by employing a multidisciplinary approach encompassing proteomics and bioinformatics analyses, as well as molecular biology assays, the study uncovered phenotypic responses linked to specific MECP2 gene mutations. These findings contribute to a better understanding of the complexity of RTT molecular pathways, confirming the high heterogeneity among the patients., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...- Published
- 2024
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25. A novel mutation in the LRSAM1 gene in a family with early onset autosomal dominant Charcot-Marie-Tooth type 2P.
- Author
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Milella G, Amati A, Lastella P, Zanfardino P, Petruzzella V, and Zoccolella S
- Subjects
- Humans, Mutation genetics, Phenotype, Ubiquitin-Protein Ligases genetics, Charcot-Marie-Tooth Disease genetics
- Abstract
Charcot-Marie-Tooth disease type 2P (CMT2P; MIM #614436) is a specific type of axonal neuropathy caused by mutations in the LRSAM1 gene, which is a RING-type E3 ubiquitin ligase. CMT2P can be inherited in two ways: as an autosomal dominant or autosomal recessive trait. In this report, we describe the clinical characteristics of a family with axonal sensory-motor neuropathy caused by a new variant of the LSRAM1 gene, which is associated with early-onset autosomal dominant CMT2P., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...
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- 2024
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26. Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization.
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Mariano V, Kanellopoulos AK, Ricci C, Di Marino D, Borrie SC, Dupraz S, Bradke F, Achsel T, Legius E, Odent S, Billuart P, Bienvenu T, and Bagni C
- Subjects
- Humans, Actins genetics, Actins metabolism, Polymerization, Adaptor Proteins, Signal Transducing genetics, Fragile X Mental Retardation Protein metabolism, Intellectual Disability genetics, Autism Spectrum Disorder genetics, Autism Spectrum Disorder metabolism
- Abstract
Background: 15q11.2 deletions and duplications have been linked to autism spectrum disorder, schizophrenia, and intellectual disability. Recent evidence suggests that dysfunctional CYFIP1 (cytoplasmic FMR1 interacting protein 1) contributes to the clinical phenotypes observed in individuals with 15q11.2 deletion/duplication syndrome. CYFIP1 plays crucial roles in neuronal development and brain connectivity, promoting actin polymerization and regulating local protein synthesis. However, information about the impact of single nucleotide variants in CYFIP1 on neurodevelopmental disorders is limited., Methods: Here, we report a family with 2 probands exhibiting intellectual disability, autism spectrum disorder, spastic tetraparesis, and brain morphology defects and who carry biallelic missense point mutations in the CYFIP1 gene. We used skin fibroblasts from one of the probands, the parents, and typically developing individuals to investigate the effect of the variants on the functionality of CYFIP1. In addition, we generated Drosophila knockin mutants to address the effect of the variants in vivo and gain insight into the molecular mechanism that underlies the clinical phenotype., Results: Our study revealed that the 2 missense variants are in protein domains responsible for maintaining the interaction within the wave regulatory complex. Molecular and cellular analyses in skin fibroblasts from one proband showed deficits in actin polymerization. The fly model for these mutations exhibited abnormal brain morphology and F-actin loss and recapitulated the core behavioral symptoms, such as deficits in social interaction and motor coordination., Conclusions: Our findings suggest that the 2 CYFIP1 variants contribute to the clinical phenotype in the probands that reflects deficits in actin-mediated brain development processes., (Copyright © 2023. Published by Elsevier Inc.) more...
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- 2024
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27. Anti-LGALS3BP antibody-drug conjugate treatment induces durable and potent antitumor response in a preclinical model of adenoid cystic carcinoma.
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Capone E, Perrotti V, Cela I, Lattanzio R, Togni L, Rubini C, Caponio VCA, Lo Muzio L, Colasante M, Giansanti F, Ippoliti R, Iacobelli S, Wick MJ, Spardy Burr N, and Sala G
- Subjects
- Animals, Humans, Disease Models, Animal, Male, Female, Adult, Middle Aged, Aged, Aged, 80 and over, Xenograft Model Antitumor Assays, Mice, Antigens, Neoplasm, Biomarkers, Tumor antagonists & inhibitors, Carcinoma, Adenoid Cystic drug therapy, Salivary Gland Neoplasms drug therapy
- Abstract
Objectives: Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically arises from glandular tissues, most commonly in the salivary glands. Although relatively rare, it represents a serious clinical issue as the management of the disease is highly complex being the only therapeutic options represented by invasive surgery and/or radiotherapy. In the present study, we have explored the potential of galectin-3 binding protein (LGALS3BP) as a novel target for antibody-drug conjugate (ADC) therapy in ACC., Materials and Methods: RNAseq was conducted on a panel of 10 ACC patient-derived xenografts (PDX)s tissues and 6 normal salivary glands to analyze LGALS3BP gene expression. Protein expression was assessed in ACC PDX and primary tumor tissues using immunohistochemistry. Anti-LGALS3BP ADC named 1959-sss/DM4, was tested in high LGALS3BP expressing ACC PDX model ST1502B., Results: RNAseq analysis revealed that LGALS3BP expression was highly expressed in ACC PDX tissues compared to normal salivary gland tissues. As evaluated by immunohistochemical analysis, LGALS3BP protein was found to be heterogeneously expressed in 10 ACC PDX and in tumor tissues derived from a cohort of 37 ACC patients. Further, treatment with 1959-sss/DM4 ADC led to durable tumor growth inhibition (TGI) in 100% of animals without observed toxicity., Conclusions: Our study provides strong evidence that LGALS3BP is a promising therapeutic target for ACC, warranting further expedited preclinical and clinical investigation., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2024
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28. Perampanel as only add-on epilepsy treatment in elderly: A subgroup analysis of real-world data from retrospective, multicenter, observational study.
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Pascarella A, Gasparini S, Manzo L, Marsico O, Torino C, Abelardo D, Cianci V, Iudice A, Bisulli F, Bonanni P, Caggia E, D'Aniello A, Di Bonaventura C, DiFrancesco JC, Domina E, Dono F, Gambardella A, Marini C, Marrelli A, Matricardi S, Morano A, Paladin F, Renna R, Piccioli M, Striano P, Ascoli M, Ferlazzo E, and Aguglia U more...
- Subjects
- Aged, Aged, 80 and over, Humans, Drug Therapy, Combination, Retrospective Studies, Seizures drug therapy, Treatment Outcome, Multicenter Studies as Topic, Observational Studies as Topic, Anticonvulsants adverse effects, Epilepsy drug therapy
- Abstract
Introduction: Drug management of epilepsy in the elderly presents unique but data on this population are scarce. This study aimed to assess the effectiveness and tolerability of perampanel (PER) used as only add-on to a background anti-seizure medication (ASM) in the elderly in a real-world setting., Methods: We performed a subgroup analysis of patients aged ≥65 years included in a previous 12-month multicenter study on adults. Treatment discontinuation, seizure frequency, and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted., Results: The sample included 65 subjects (mean age: 75.7 ± 7.2 years), with mainly focal (73.8%) epilepsy. The mean PER daily dose was ≈4 mg during all follow-up. Retention rates at 3, 6, and 12 months were 90.5%, 89.6%, and 79.4%ly. The baseline median normalized per 28-day seizure number significantly decreased at 3-, 6- and 12-month visits. One year after PER introduction, the responder rate (≥50% reduction in baseline seizure frequency) was 89.7%, with a seizure freedom rate of 72.4%. Adverse events occurred in 22 (34.9%) patients with dizziness and irritability being the most frequent. No major differences between early (41 patients, 63.1%), and late add-on groups were observed., Conclusion: Adjunctive PER was effective and well-tolerated when used as only add-on treatment in elderly people with epilepsy in clinical practice, thus representing a suitable therapeutic option in this age category., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2023
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29. River widening in mountain and foothill areas during floods: Insights from a meta-analysis of 51 European Rivers.
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Ruiz-Villanueva V, Piégay H, Scorpio V, Bachmann A, Brousse G, Cavalli M, Comiti F, Crema S, Fernández E, Furdada G, Hajdukiewicz H, Hunzinger L, Lucía A, Marchi L, Moraru A, Piton G, Rickenmann D, Righini M, Surian N, Yassine R, and Wyżga B more...
- Abstract
River widening, defined as a lateral expansion of the channel, is a critical process that maintains fluvial ecosystems and is part of the regular functioning of rivers. However, in areas with high population density, channel widening can cause damage during floods. Therefore, for effective flood risk management it is essential to identify river reaches where abrupt channel widening may occur. Despite numerous efforts to predict channel widening, most studies have been limited to single rivers and single flood events, which may not be representative of other conditions. Moreover, a multi-catchment scale approach that covers various settings and flood magnitudes has been lacking. In this study, we fill this gap by compiling a large database comprising 1564 river reaches in several mountain regions in Europe affected by floods of varying magnitudes in the last six decades. By applying a meta-analysis, we aimed to identify the types of floods responsible for more extensive widening, the river reach types where intense widening is more likely to occur, and the hydraulic and morphological variables that explain widening and can aid in predicting widening. Our analysis revealed seven groups of reaches with significantly different responses to floods regarding width ratios (i.e., the ratio between channel width after and before a flood). Among these groups, the river reaches located in the Mediterranean region and affected by extreme floods triggered by short and intense precipitation events showed significantly larger widening than other river reaches in other regions. Additionally, the meta-analysis confirmed valley confinement as a critical morphological variable that controls channel widening but showed that it is not the only controlling factor. We proposed new statistical models to identify river reaches prone to widening, estimate potential channel width after a flood, and compute upper bound width ratios. These findings can inform flood hazard evaluations and the design of mitigation measures., 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 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2023
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30. Melatonin MT 1 receptors as a target for the psychopharmacology of bipolar disorder: A translational study.
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Tassan Mazzocco M, Pisanu C, Russo L, Acconcia C, Cambiaghi M, De Girolamo S, Squassina A, Cherchi L, Monzani E, Scebba F, Angeloni D, De Gregorio D, Nasini S, Dall'Acqua S, Sut S, Suprani F, Garzilli M, Guiso B, Pulcinelli V, Iaselli MN, Pinna I, Somaini G, Arru L, Corrias C, Paribello P, Pinna F, Gobbi G, Valtorta F, Carpiniello B, Manchia M, and Comai S more...
- Subjects
- Humans, Mice, Animals, Receptor, Melatonin, MT1 genetics, Receptor, Melatonin, MT2 genetics, Receptor, Melatonin, MT2 agonists, Bipolar Disorder drug therapy, Bipolar Disorder genetics, Melatonin therapeutic use, Melatonin pharmacology, Psychopharmacology
- Abstract
The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT
1 and MT2 , plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...- Published
- 2023
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31. Quantitative and qualitative approaches for CEC prioritization when reusing reclaimed water for irrigation needs - A critical review.
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Verlicchi P, Lacasa E, and Grillini V
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- Humans, Agricultural Irrigation methods, Anti-Bacterial Agents, Soil, Wastewater, Water
- Abstract
The use of reclaimed water for irrigation is an option that is becoming increasingly widespread to alleviate water scarcity and to cope with drought. However, reclaimed water, if used for irrigation, may introduce Contaminants of Emerging Concern (CECs) into the agroecosystems, which may be taken up by the crops and subsequently enter the food chain. The number of CECs is steadily increasing due to their continuous introduction on the market for different uses. There is an urgent need to draw up a short list of potential high priority CECs, which are substances that could be taken up by plants and accumulated in food produce, and/or that could have negative effects on human health and the environment. This review presents and discusses the approaches developed to prioritize CECs when reclaimed water is (re-)used for irrigation. They are divided into quantitative methodologies, which estimate the risk for environmental compartments (soil and water), predators and humans through equations, and qualitative methodologies, which are instead conceptual frameworks or procedures based on the simultaneous combination of data/information/practices with the judgment of experts. Three antibiotics (erythromycin, sulfamethoxazole and ciprofloxacin), one estrogen (17-α ethinylestradiol) and one analgesic (ibuprofen) were found on at least two priority lists, although comparison among studies is still difficult. The review remarks that it is advisable to harmonize the different methodologies in order to identify the priority CECs to include in monitoring programs in reclaimed water reuse projects and to ensure a high level of protection for humans and the environment., 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 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2023
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32. Incidence and management of idiopathic peri-lead edema (IPLE) following deep brain stimulation (DBS) surgery: Case series and review of the literature.
- Author
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Giordano M, Innocenti N, Rizzi M, Rinaldo S, Nazzi V, Eleopra R, and Levi V
- Subjects
- Humans, Incidence, Electrodes, Implanted adverse effects, Edema, Deep Brain Stimulation adverse effects, Parkinson Disease complications
- Abstract
Objective: Idiopathic peri-lead edema (IPLE) is being increasingly described as a potential complication occurring after DBS surgery. Its incidence and relationship to post-operative symptoms, though, are still poorly defined and its understanding and management yet limited., Methods: We reviewed delayed (≥ 72 h) post-operative CT imaging of patients who underwent DBS surgery at our Institution. A comparison of clinical and laboratory findings was carried out between patients with IPLE and controls., Results: 61 patients, accounting for 115 electrodes, were included. Incidence of IPLE was 37.7 % per patient and 29.5 % per electrode. Patients with IPLE were significantly older than controls (52.82 ± 15.65 years vs 44.73 ± 18.82 years, p = 0.04). There was no difference in incidence of new-onset neurological symptoms between patients with IPLE and controls. Longer operative time (180.65 ± 34.30 min vs 158.34 ± 49.28 min, p = 0.06) and a greater number of MERs per electrode were associated with IPLE (3.37 ± 1.21 vs 3.00 ± 1.63, p = 0.089), though these comparisons did not meet the statistical significance. None of the patients with IPLE underwent hardware removal, with IPLE vanishing spontaneously over months., Conclusions: IPLE is an underestimated, benign event that may occur after DBS surgery. Age, longer operative time and MER use may represent risk factors for IPLE formation, but further studies are needed. The presence of post-operative neurological symptoms and fever was not associated with IPLE presence, highlighting its benign nature and suggesting that empiric treatment may not be always justified., (Copyright © 2023. Published by Elsevier B.V.) more...
- Published
- 2023
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33. Platelet defects in cirrhosis: Fact or fiction.
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Violi F, Pignatelli P, and Cammisotto V
- Published
- 2023
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34. A reliable and replicable test protocol for the mechanical evaluation of synthetic meshes.
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Civilini V, Giacalone V, Audenino AL, and Terzini M
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- Humans, Tensile Strength, Materials Testing, Polypropylenes, Herniorrhaphy, Prostheses and Implants, Surgical Mesh
- Abstract
Despite the worldwide spread of surgical meshes in abdominal and inguinal surgery repair, the lack of specific standards for mechanical characterization of synthetic meshes, used in hernia repair and urogynecologic surgery, makes performance comparison between prostheses undoubtedly difficult. This consequently leads to the absence of acknowledged specifications about the mechanical requirements that synthetic meshes should achieve in order to avoid patient discomfort or hernia recurrences. The aim of this study is to provide a rigorous test protocol for the mechanical comparison between surgical meshes having the same intended use. The test protocol is composed of three quasi-static test methods: (1) ball burst test, (2) uniaxial tensile test, and (3) suture retention test. For each test, post-processing procedures are proposed to compute relevant mechanical parameters from the raw data. Some of the computed parameters, indeed, could be more suitable for comparison with physiological conditions (e.g., membrane strain and anisotropy), while others (e.g., uniaxial tension at rupture and suture retention strength) are reported as they provide useful mechanical information and could be convenient for comparisons between devices. The proposed test protocol was applied on 14 polypropylene meshes, 3 composite meshes, and 6 urogynecologic devices to verify its universal applicability towards meshes of different types and produced by various manufacturers, and its repeatability in terms of coefficient of variation. The test protocol resulted easily applicable to all the tested surgical meshes with intra-subject variability characterized by coefficient of variations settled around 0.05. Its use within other laboratories could allow the determination of the inter-subject variability assessing its repeatability among users of alternative universal testing machines., 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 Ltd. All rights reserved.) more...
- Published
- 2023
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35. High frequency of BCL2 gene rearrangement-negative follicular lymphoma in northwestern Italy.
- Author
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Magnoli F, Marchiori D, Facchi S, Martin V, Campiotti L, Merli M, Sessa F, Tibiletti MG, and Uccella S
- Subjects
- Humans, Translocation, Genetic, In Situ Hybridization, Fluorescence, Tumor Suppressor Protein p53 genetics, Proto-Oncogene Proteins c-bcl-2 genetics, Gene Rearrangement, Proto-Oncogene Proteins c-bcl-6 genetics, Lymphoma, Follicular genetics
- Abstract
BCL2 rearrangement is reported to be an early pathogenetic event in follicular lymphoma (FL) and it is considered as a reliable marker in the follow up of the disease. We aimed to investigate the frequency of BCL2 rearrangement in FLs from northwestern Italy, to evaluate their clinicopathological features, and to investigate alternative genetic aberrations in BCL2-negative FLs. We collected a series of 76 consecutive FLs diagnosed between 2013 and 2016. All lymphomas underwent histopathological review. Interphasic fluorescent in situ hybridization (FISH) was performed with break apart probes targeting BCL2, IGH, BCL6 and MYC on paraffin embedded (PE) and fresh frozen (FF) specimens. 1p36 region and p53 locus in BLC2-negative cases were investigated using dual color probes. Karyotype analysis was available in a subset of cases. BCL2 rearrangements were detected in 39 cases (51,3%). Of the remaining 37, 6 showed IGH rearrangement, and were further tested: 1 showed variant BCL2 translocation, 1 had BCL6 rearrangement, and the other 4 were negative for further gene rearrangements. FISH on FF specimens detected small BCL2+ clones in cases otherwise categorized as BCL2-. 1p36 and p53 deletion were observed in 1 and 8 BCL2- FLs, respectively. Karyotype analysis documented 3q, 1p and BCL6 alternative abnormalities in 3 cases. In conclusion, BCL2 rearrangement is not a constant finding in FL, its frequency being probably affected by geographical factors. Thus, it should not be considered as a reliable molecular marker in the follow up of the disease, unless it is found to be present at the initial diagnosis of FL. Alternative genetic aberrations exist in BCL2-negative cases., Competing Interests: Declaration of Competing Interest All authors disclose no financial conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...
- Published
- 2023
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36. Immediate prepectoral breast reconstruction using an ADM with smooth round implants: A prospective observational cohort study.
- Author
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di Pompeo FS, Firmani G, Paolini G, Amorosi V, Briganti F, and Sorotos M
- Subjects
- Female, Humans, Mastectomy methods, Prospective Studies, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Acellular Dermis, Breast Neoplasms surgery, Mammaplasty methods
- Abstract
Prepectoral breast reconstruction using acellular dermal matrices (ADMs) is well established and used in candidates for nipple/skin-sparing mastectomies; it is based on many different matrices and a great variability in breast implant selection. We describe our experience and clinical outcomes using Braxon® ADMs and smooth round breast implants. Females aged 18-80 years who underwent mastectomies with immediate prepectoral reconstruction between April 2019 and April 2021 were prospectively included. Complications were classified as mastectomy-related (hematoma, necrosis) or reconstruction-related (seroma, infection, red breast syndrome). Binary logistic regression analysis was performed to assess correlation between complication rate and selected variables, which were analyzed per breast with Kruskal-Wallis H test. Fifty-eight patients (102 breasts) received 45 bilateral and 12 unilateral procedures. Drains collected 485.9 cc [range: 100-1260] and were removed 15.7 days [range: 6-29] postoperatively. We report 41 complications (40.2%): 33 mastectomy-related, 8 reconstruction-related. Reoperation occurred in 14 patients: 7 wound debridement and revisions under local anesthesia; and 7 explantation. Implant loss rate was 6.8%. Mastectomy and reconstruction complications were not correlated with any variable. In conclusion, we found prepectoral reconstruction with Braxon® ADMs and smooth round implants to be associated with acceptable complication rates that are not influenced by any patient- or surgery-related factors. Drainage volume is comparable to other breast implant reconstructive techniques, but drains are left in place for longer., Competing Interests: Conflicts of interest The corresponding author (FSdP) would like to disclose that he serves as a paid consultant for BellaSeno GmbH, that he received reimbursements from ICEAG in 2015 and SCHEER-WG in 2019, 2020, and 2021, and is a member of Notified Body 0373 carrying out CE Mark certification activities for the Italian Ministry of Health for the year 2021. They have no ownerships or investments to disclose. All other authors hereby certify, that to the best of their knowledge no financial support or benefits has been received, neither by themselves directly, nor by any member of their immediate family or any individual or entity with whom or with which they may have a significant relationship from any commercial source that is related directly or indirectly to the scientific work that is reported on in the article., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.) more...
- Published
- 2023
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37. Left Mesial Temporooccipital PLNTY: Supracerebellar Transtentorial Approach in Epilepsy Surgery.
- Author
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Rizzi M, Castelli N, Di Giacomo R, Cojazzi V, Innocenti N, Levi V, Nazzi V, and Schiariti M
- Subjects
- Female, Humans, Temporal Lobe surgery, Brain pathology, Seizures pathology, Epilepsy complications, Brain Neoplasms surgery
- Abstract
The supracerebellar transtentorial approach for the resection of brain lesion at the level of the mesial temporooccipital region is underused in the field of epilepsy surgery, despite the theoretical advantage of sparing normal brain structures, in particular in the dominant hemisphere for language. Hereby we present the case of a patient with a low-grade epilepsy associated tumor, presenting with weekly drug-resistant focal seizures, treated by a supracerebellar transtentorial lesionectomy. Surgery was uneventful and the histopathology revealed a pleomorphic low-grade neuroepithelial tumor of the young patient. At the 6-month follow-up, the patient did not present neurologic deficits and she never presented with seizures after surgery, so antiepileptic drug tapering started. The integration of supracerebellar transtentorial approach in the "armory" of the epilepsy neurosurgeon requires a dedicated expertise and an anesthesiologic setting used to manage the semisitting position; on the other hand, it could provide a relevant option to provide safe and complete lesionectomy in the mesial temporooccipital region, together with the more classical sublobar and transcerebral approaches (Video 1)., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...
- Published
- 2023
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38. Global patterns and drivers of influenza decline during the COVID-19 pandemic.
- Author
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Bonacina F, Boëlle PY, Colizza V, Lopez O, Thomas M, and Poletto C
- Subjects
- Humans, Pandemics, North America, Weather, Influenza, Human epidemiology, COVID-19 epidemiology
- Abstract
Objectives: The influenza circulation reportedly declined during the COVID-19 pandemic in many countries. The occurrence of this change has not been studied worldwide nor its potential drivers., Methods: The change in the proportion of positive influenza samples reported by country and trimester was computed relative to the 2014-2019 period using the FluNet database. Random forests were used to determine predictors of change from demographical, weather, pandemic preparedness, COVID-19 incidence, and pandemic response characteristics. Regression trees were used to classify observations according to these predictors., Results: During the COVID-19 pandemic, the influenza decline relative to prepandemic levels was global but heterogeneous across space and time. It was more than 50% for 311 of 376 trimesters-countries and even more than 99% for 135. COVID-19 incidence and pandemic preparedness were the two most important predictors of the decline. Europe and North America initially showed limited decline despite high COVID-19 restrictions; however, there was a strong decline afterward in most temperate countries, where pandemic preparedness, COVID-19 incidence, and social restrictions were high; the decline was limited in countries where these factors were low. The "zero-COVID" countries experienced the greatest decline., Conclusion: Our findings set the stage for interpreting the resurgence of influenza worldwide., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2023
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39. Gut dysbiosis, endotoxemia and clotting activation: A dangerous trio for portal vein thrombosis in cirrhosis.
- Author
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Violi F, Pignatelli P, Castellani V, Carnevale R, and Cammisotto V
- Subjects
- Humans, Portal Vein pathology, Lipopolysaccharides, Dysbiosis complications, Dysbiosis pathology, Liver Cirrhosis complications, Liver Cirrhosis pathology, Endotoxemia complications, Endotoxemia pathology, Venous Thrombosis etiology, Thrombosis etiology, Thrombosis pathology
- Abstract
Liver cirrhosis (LC) is associated with portal venous thrombosis (PVT) in roughly 20% of cirrhotic patients but the underlying mechanism is still unclear. Low-grade endotoxemia by lipopolysaccharides (LPS), a component of outer gut microbiota membrane, is detectable in the portal circulation of LC and could predispose to PVT. LPS may translocate into systemic circulation upon microbiota dysbiosis-induced gut barrier dysfunction, that is a prerequisite for enhanced gut permeability and ensuing endotoxemia. Experimental and clinical studies provided evidence that LPS behaves a pro-thrombotic molecule so promoting clotting and platelet activation. Experiments conducted in the portal circulation of cirrhotic patients showed the existence of LPS-related enhanced thrombin generation as well as endothelial dysfunction, venous stasis, and platelet activation. The review will analyze 1) the pro-thrombotic role of endotoxemia in the context of LC 2) the biological plausibility linking endotoxemia with PVT and 3) the potentially interventional tools to lower endotoxemia and eventually hypercoagulation., (Copyright © 2022. Published by Elsevier Ltd.) more...
- Published
- 2023
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40. Vanishing contrast-enhancing peri-lead oedema following deep brain stimulation surgery: A case report.
- Author
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Innocenti N, Giordano M, Messina G, Nazzi V, Eleopra R, and Levi V
- Subjects
- Humans, Edema, Magnetic Resonance Imaging methods, Deep Brain Stimulation adverse effects, Deep Brain Stimulation methods
- Abstract
Idiopathic peri-lead oedema (IPLE) after deep brain stimulation (DBS) surgery is still a poorly understood phenomenon. It is usually asymptomatic and does not present contrast enhancement at the post-operative Magnetic Resonance Imaging (MRI). Here we present the rare case of contrast-enhancing IPLE occurring in a completely asymptomatic patient vanishing spontaneously at the radiological follow-up at one month. The radiological picture raised the concerns of peri-lead abscess, but the absence of clinical and laboratory signs of infection and the benefit of DBS over the patient's dystonic symptoms prompted a more conservative approach. To our knowledge, this is the first reported case of asymptomatic contrast-enhancing IPLE conservatively managed., Competing Interests: Competing interests The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.) more...
- Published
- 2022
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41. Generation and characterization of CSSi016-A (9938) human pluripotent stem cell line carrying two biallelic variants in MTMR5/SBF1 gene resulting in a case of severe CMT4B3.
- Author
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Maria Turco E, Maria Giada Giovenale A, Rotundo G, Mazzoni M, Zanfardino P, Frezza K, Torrente I, Mary Carletti R, Damiani D, Santorelli FM, Luigi Vescovi A, Petruzzella V, and Rosati J
- Subjects
- Child, Humans, Female, Cell Line, Intracellular Signaling Peptides and Proteins genetics, Pluripotent Stem Cells, Charcot-Marie-Tooth Disease genetics
- Abstract
Charcot-Marie-Tooth type 4B3 (CMT4B3) is a rare subtype of hereditary neuropathy associated with variants in the MTMR5/SBF1 gene. Herein, we report the generation and characterization of a hiPSC line from a 12-year-old Italian girl with early onset severe polyneuropathy with motor and axonal involvement, harboring biallelic variants in the MTMR5/SBF1 gene. Fibroblasts were reprogrammed using non-integrating episomal plasmids, and iPSCs successfully passed the stemness and pluripotency tests. Patient-specific hiPSCs were produced to obtain a disease model for the study of this rare condition., 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 © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2022
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42. CD44-targeted nanoparticles with GSH-responsive activity as powerful therapeutic agents against breast cancer.
- Author
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Brindisi M, Curcio M, Frattaruolo L, Cirillo G, Leggio A, Rago V, Nicoletta FP, Cappello AR, and Iemma F
- Subjects
- Humans, Female, Hyaluronic Acid therapeutic use, Doxorubicin pharmacology, Doxorubicin therapeutic use, Cell Line, Tumor, Hyaluronan Receptors, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Nanoparticles
- Abstract
DOX-loaded nanoparticles able to actively target CD44-receptors and respond to redox stimuli were proposed as non-conventional chemotherapeutic strategy in breast cancer. A covalent conjugate of human serum albumin and hyaluronic acid was prepared and assembled by a GSH-mediated desolvation in disulfide-crosslinked solid nanoparticles with mean diameter of 120 nm ± 3.4. The effective internalization of nanoparticles in cancer cells via CD44-receptors, together with the more efficient intracellular release, resulted in a significant increase of drug efficacy, with IC
50 reduced from 0.9959 and 2.516 μg mL-1 to 0.4014 and 0.3094 μg mL-1 for MCF-7 and MDA-MB-231, respectively. Conversely, no enhancement in drug toxicity was recorded in healthy MCF-10A cells. The efficacy of the proposed formulation was further investigated in the different biological steps involved in metastasis process, paving the way for further in vivo experiments., 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 © 2022 Elsevier B.V. All rights reserved.) more...- Published
- 2022
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43. Investigation on the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract in an in vitro model of excitotoxicity.
- Author
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Borgonetti V, Biagi M, Galeotti N, Manetti F, and Governa P
- Subjects
- Humans, Brain-Derived Neurotrophic Factor, Molecular Structure, Glutamic Acid, Plant Extracts pharmacology, Cannabidiol pharmacology, Cannabis, Neuroprotective Agents pharmacology, Neuroblastoma
- Abstract
The purpose of this study was to evaluate the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract (CSE) and its main constituents, cannabidiol and β-caryophyllene. An in vitro model of glutamate-induced neuronal excitotoxicity using SH-SY5Y cells was optimized. The impact of CSE on glutamate-impaired cell viability, brain-derived neurotrophic factor release, CB1 protein expression, and ERK levels was evaluated. The involvement of CB1 modulation was verified by the cotreatment with the CB1 antagonist AM4113. CSE was able to significantly protect SH-SY5Y from glutamate-impaired cell viability, and to counteract the changes in brain-derived neurotrophic factor levels, with a mechanism of action involving ERK modulation. Moreover, CSE completely reversed the reduction of CB1 receptor expression induced by glutamate, and the presence of the CB1 antagonist AM4113 reduced CSE effectiveness, suggesting that CBr play a role in the modulation of neuronal excitotoxicity. This work demonstrated the in vitro effectiveness of CSE as a neuroprotective agent, proposing the whole cannabis phytocomplex as a more effective strategy, compared to its main constituents alone, and suggested further investigations by using more complex cell models before moving to in vivo studies., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.) more...
- Published
- 2022
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44. Quantitative Myocardial Perfusion With Simultaneous-Multislice Stress CMR for Detection of Significant Coronary Artery Disease.
- Author
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Nazir MS, Milidonis X, McElroy S, Ryan M, Yazdani M, Kunze K, Hajhosseiny R, Vergani V, Stäb D, Speier P, Neji R, Ismail TF, Perera D, Plein S, Roujol S, and Chiribiri A
- Subjects
- Coronary Angiography, Coronary Circulation, Humans, Perfusion, Predictive Value of Tests, Coronary Artery Disease diagnostic imaging, Myocardial Perfusion Imaging
- Published
- 2022
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45. Covid-19 and beyond: Broadening horizons about social media use in oncology. A survey study with healthcare professionals caring for youth with cancer.
- Author
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Rost M, Espeli V, Ansari M, von der Weid N, Elger BS, and De Clercq E
- Abstract
Objectives: The study aimed to explore the attitudes of Swiss healthcare professionals toward the use of social media in adolescent and young adult oncology, and to examine whether the ongoing social restrictions due to COVID-19 might have altered these attitudes., Methods: This research was a survey study. The subjects were healthcare providers working in pediatric or adult oncology settings in Switzerland. 62 providers completed the survey. We performed descriptive and inferential statistical analyses., Results: While considered useful for various professional aspects (professional life 62.1%, educational purposes 72.7%, networking 83.3%, patient engagement 57.6%, clinical trial recruitment 51.5%), only a small proportion of participants actually used social media for professional reasons weekly (32.8%). Just over half considered themselves skillful in using these platforms (56.1%). Regression analysis revealed that self-assessed skillfulness with social media, the Covid-19 impact on attitudes, and the oncology setting, significantly predicted assessment of the usefulness of social media. Although, in answers to open items, institutional guidelines were deemed crucial to improve social media use, many respondents seemed unaware of their existence (50.8%). Only a minority reported an impact of Covid-19 on their attitudes towards the professional implementation of social media (25.0%)., Conclusion: The global health crisis creates important challenges for young patients with cancer and their healthcare providers. In times of social restrictions, social media may be a promising tools to facilitate health information provision, connectivity, and patient care. Virtual mentorship and targeted social media training interventions might be a good way to improve familiarity with using social media and to increase awareness about existing ethical guidelines for their use., Competing Interests: 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., (© 2022 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd.) more...
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- 2022
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46. High-resolution non-contrast free-breathing coronary cardiovascular magnetic resonance angiography for detection of coronary artery disease: validation against invasive coronary angiography.
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Nazir MS, Bustin A, Hajhosseiny R, Yazdani M, Ryan M, Vergani V, Neji R, Kunze KP, Nicol E, Masci PG, Perera D, Plein S, Chiribiri A, Botnar R, and Prieto C
- Subjects
- Coronary Angiography methods, Female, Humans, Magnetic Resonance Angiography, Magnetic Resonance Spectroscopy, Predictive Value of Tests, Prospective Studies, Sensitivity and Specificity, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease pathology, Coronary Stenosis, Myocardial Perfusion Imaging methods
- Abstract
Background: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA)., Methods: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm
3 ) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA., Results: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively., Conclusion: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required., (© 2022. The Author(s).) more...- Published
- 2022
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47. De novo myoclonic status epilepticus in Alzheimer disease.
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Pascarella A, Cianci V, Manzo L, Neri S, Gasparini S, Santangelo D, Ferlazzo E, and Aguglia U
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- Electroencephalography, Humans, Alzheimer Disease complications, Epilepsies, Myoclonic, Status Epilepticus complications
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- 2022
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48. Homogentisic acid induces autophagy alterations leading to chondroptosis in human chondrocytes: Implications in Alkaptonuria.
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Galderisi S, Milella MS, Rossi M, Cicaloni V, Rossi R, Giustarini D, Spiga O, Tinti L, Salvini L, Tinti C, Braconi D, Millucci L, Lupetti P, Prischi F, Bernardini G, and Santucci A
- Subjects
- Alkaptonuria metabolism, Apoptosis drug effects, Cartilage, Articular drug effects, Cell Line, Chondrocytes cytology, Homogentisic Acid pharmacology, Humans, Ochronosis metabolism, Oxidative Stress drug effects, Signal Transduction, Alkaptonuria prevention & control, Autophagy drug effects, Biomarkers metabolism, Homogentisate 1,2-Dioxygenase metabolism, Homogentisic Acid metabolism
- Abstract
Alkaptonuria (AKU) is an ultra-rare genetic disease caused by a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD) leading to the accumulation of homogentisic acid (HGA) on connective tissues. Even though AKU is a multi-systemic disease, osteoarticular cartilage is the most affected system and the most damaged tissue by the disease. In chondrocytes, HGA causes oxidative stress dysfunctions, which induce a series of not fully characterized cellular responses. In this study, we used a human chondrocytic cell line as an AKU model to evaluate, for the first time, the effect of HGA on autophagy, the main homeostasis system in articular cartilage. Cells responded timely to HGA treatment with an increase in autophagy as a mechanism of protection. In a chronic state, HGA-induced oxidative stress decreased autophagy, and chondrocytes, unable to restore balance, activated the chondroptosis pathway. This decrease in autophagy also correlated with the accumulation of ochronotic pigment, a hallmark of AKU. Our data suggest new perspectives for understanding AKU and a mechanistic model that rationalizes the damaging role of HGA., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...
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- 2022
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49. sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.
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Soldavini CM, Di Martino D, Sabattini E, Ornaghi S, Sterpi V, Erra R, Invernizzi F, Tine' G, Giardini V, Vergani P, Ossola MW, and Ferrazzi E
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- Adolescent, Adult, Biomarkers blood, COVID-19 blood, Case-Control Studies, Female, Follow-Up Studies, Humans, Hypertension, Pregnancy-Induced blood, Hypertension, Pregnancy-Induced diagnosis, Multivariate Analysis, Pregnancy, Severity of Illness Index, Young Adult, COVID-19 complications, Hypertension, Pregnancy-Induced virology, Placenta Growth Factor blood, Vascular Endothelial Growth Factor Receptor-1 blood
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Objectives: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group., Study Design: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment., Main Outcome Measures: sFlt-1/PlGF ratio., Results: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection., Conclusions: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.) more...
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- 2022
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50. Safety and Feasibility of Home Transfusions in Pediatric Palliative Care: A Preliminary Report.
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De Zen L, Del Rizzo I, Vendrametto V, Nicolardi F, Vaccher S, Dall'Amico R, Rabusin M, Barbi E, and Passone E
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- Blood Transfusion, Child, Feasibility Studies, Humans, Palliative Care methods, Home Care Services, Hospice and Palliative Care Nursing, Neoplasms
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Background: While hematological symptoms are considered difficult to manage in a Pediatric Palliative Care setting, home may still represent a safe and convenient place for transfusions in patients with advanced malignancy or chronic conditions. This research focuses on the safety and feasibility of a home transfusion program., Methods: This is a case series of patients between 0 and 18 years diagnosed with advanced malignancy or incurable chronic conditions and eligible to Pediatric Palliative Care who received home platelet or packed red cell transfusions. For all patients, we recorded adverse events such as acute hemolytic reactions, allergic reactions, or any emergency condition requiring hospital admission, equipment failure, blood product transport or storage errors, errors in patient identification, and personnel safety issues. We explored parental satisfaction with a Likert-type questionnaire and short open questions., Results: We reviewed 101 transfusion procedures for six patients in Pediatric Palliative Care performed by the Regional Pediatric Palliative Care network between 2014 and 2020. We did not report any adverse effects. Families reported satisfaction and a sense of safety and positively evaluated the opportunity of having transfusion at home to minimize the disruption in everyday life. The cost analysis resulted in a consistent saving for the Regional Health System., Conclusion: This study supports the safety and feasibility of home transfusion in Pediatric Palliative Care., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.) more...
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- 2022
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