Presence of Skin α-Synuclein Deposits Discriminates Parkinson's Disease from Progressive Supranuclear Palsy and Corticobasal Syndrome

Background: Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson's disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited. Objective: We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD. Methods: We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin nerves by immunofluorescence. Results: Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p <  0.001, Chi-square). The two p-syn positive patients were diagnosed with PSP and CBS, respectively. Although clinical and MRI findings supported these diagnoses, both patients had some atypical features more typical of synucleinopathies. Conclusion: The detection of skin p-syn deposits may help in the differential diagnosis of parkinsonism. Indeed, in this study, all PD patients and only two out of 26 with a clinical diagnosis of PSP/CBS had skin p-syn deposits. Furthermore, these two patients showed clinical features that could suggest an atypical synucleinopathy presentation or a mixed pathology

A new risk stratification score for the management of ultrasound‐detected B3 breast lesions

To develop a predictive scoring system for ultrasound-detected B3 lesions at ultrasound-guided core needle biopsy (US-CNB). A total of 2724 consecutive US-CNBs performed in our Institution (January 2011 to December 2014) were retrospectively reviewed. Inclusion criteria were as follows: (a) histopathological examination of the entire lesion or (b) availability of radiologic follow-up (FUP) ≥24 months. Patient- and lesion-related variables-patients' age, lesion consistency, lesion size, vascularization, BI-RADS category, and US-CNB result-were analyzed. Positive predictive values (PPVs) for malignancy were calculated correlating US-CNB results with excision histology or FUP. A scoring system for underlying malignancy was developed using risk factors weighting. A total of 102 B3 lesions were included: 27 atypical ductal hyperplasia (26.5%), 5 lobular intraepithelial neoplasia (4.9%), 32 radial scar (31.4%), 37 papillary lesions (36.3%), and 1 fibroepithelial lesion (0.9%). Surgery was performed on 71/102 (69.6%) lesions, and 22/71 were malignant; the remaining 31/102 lesions (30.4%) were unchanged at FUP. The overall PPV for malignancy was 21.6%. Patients' age (odds ratio [OR] = 3.63, P = 0.008), lesion consistency (OR = 5.96, P = 0.001), BI-RADS category (OR = 17.52, P < 0.001), and CNB result (OR = 3.6, P = 0.008) were associated with a higher risk of malignancy underestimation and selected as risk factors in the score definition. Two risk groups were identified: low (0-2 points) and high risk (3-5 points), with significantly different risk of malignancy underestimation (8.0% vs 59.3%, P < 0.001). The proposed score helps to predict the risk of malignancy underestimation and choose the management of B3 lesions at US-CNB

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&amp;Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients

Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis

open14noClinical signs of upper motor neuron (UMN) involvement are important in the diagnosis of amyotrophic lateral sclerosis (ALS) though are often difficult to analyze. Many studies using both qualitative and quantitative evaluations have reported abnormal Magnetic Resonance Imaging (MRI) findings at the level of the pyramidal pathway in patients with ALS. Although the most interesting results were obtained by quantitative studies using advanced MR techniques, the qualitative evaluation of MRI images remains the most-used in clinical practice. We evaluated the diagnostic and prognostic contribution of conventional 3T-MRI in the clinical work-up of ALS patients. Two neuroradiologists retrospectively assessed 3T-MRI data of 93 ALS patients and 89 controls. The features of interest were corticospinal tract (CST) T2/FLAIR hyperintensity, motor cortex (MC) T2*/SWI hypointensity, and selective MC atrophy. All MRI features were significantly more prevalent in ALS patients than in controls. The simultaneous presence of CST FLAIR hyperintensity and MC SWI hypointensity was associated with the highest diagnostic accuracy (sensitivity: 70%; specificity: 81%; positive predictive value, PPV: 90%; negative predictive value, NPV: 51%; accuracy: 73%) and a shorter survival (HR: 6.56,p= 0.002). Conventional 3T-MRI can be a feasible tool to detect specific qualitative changes based on UMN involvement and to support clinical diagnosis of ALS. Importantly, CST FLAIR hyperintensity and MC SWI hypointensity are predictors of shorter survival in ALS patients.openRizzo, Giovanni; Marliani, Anna Federica; Battaglia, Stella; Albini Riccioli, Luca; De Pasqua, Silvia; Vacchiano, Veria; Infante, Rossella; Avoni, Patrizia; Donadio, Vincenzo; Passaretti, Massimiliano; Bartolomei, Ilaria; Salvi, Fabrizio; Liguori, Rocco; On Behalf Of The BoReALS Group, nullRizzo, Giovanni; Marliani, Anna Federica; Battaglia, Stella; Albini Riccioli, Luca; De Pasqua, Silvia; Vacchiano, Veria; Infante, Rossella; Avoni, Patrizia; Donadio, Vincenzo; Passaretti, Massimiliano; Bartolomei, Ilaria; Salvi, Fabrizio; Liguori, Rocco; On Behalf Of The BoReALS Group, nul

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Caratterizzazione sensoriale della proteina dolcificante MNEI

Le proteine dolci costituiscono un'accattivante alternativa ad alcuni dei più tradizionali dolcificanti, come il saccarosio, perché rispondono all???esigenza dei consumatori sempre più orientati verso prodotti con un basso contenuto calorico. Il presente lavoro è incentrato sulla caratterizzazione sensoriale di una proteina dolcificante modificata, MNEI, ottenuta attraverso espressione ricombinante in cellule di E. coli con rese elevate. In particolare sono state valutate le soglie di percezione (SP) e di riconoscimento (SR) della proteina sottoposta a diverse condizioni sperimentali, con l???obiettivo di validarne un suo impiego in campo alimentare, nel settore delle bevande. Gli obiettivi specifici sono stati lo studio dell???effetto della concentrazione di sali, dei valori di pH, di storia termica e di temperatura d???assaggio, sulle SP e SR. Lo studio delle SP e SR della proteina MNEI è stato effettuato utilizzando soluzioni modello, composte da acqua, proteina e in taluni casi da diverse quantità di acido citrico. Per la valutazione delle soglie della proteina sono stati utilizzati due metodi sensoriali già ampiamente applicati: ???Metodo della Differenza da un Riferimento??? e ???Metodo dei Limiti???. È stato inoltre usato un metodo modificato, che introduceva la richiesta di informazioni di tipo qualitativo nelle stesse sedute del test della ???Differenza da un Riferimento???. I risultati sperimentali hanno evidenziato un effetto significativo della concentrazione di sali sulla SP: più l???acqua è ricca in sali, più si alza la soglia di percezione della proteina. Anche la temperatura di assaggio delle soluzioni ha un effetto significativo sulla SP: a 10°C la SP è più alta che a 20°C. Né le variazioni di pH né la storia termica influenzano le soglie della MNEI, confermando che la proteina è stabile sia alle alte temperature che a bassi valori di pH. La richiesta di informazioni anche qualitative agli assaggiatori durante i test di valutazione della soglia non migliora la validità dei risultati ottenuti

Clinical Reasoning: Young woman with orbital pain and diplopia

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Persistence of limb dystonia and myoclonus during sleep in corticobasal syndrome: a case series

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