43 research outputs found
The effects of safinamide according to gender in Chinese parkinsonian patients
No full textAbstract The incidence and prevalence of Parkinson’s disease (PD) is expected to raise dramatically over the next decades. Gender-related differences are not yet widely recognized, particularly regarding the response to dopaminergic medications. To analyse gender differences in the clinical effects of safinamide, compared to placebo, in Chinese PD patients of the pivotal XINDI trial. The XINDI study was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Patients were followed for 16 weeks receiving safinamide or placebo as add-on to levodopa. The primary efficacy endpoint was the change in the mean total daily OFF time. Secondary efficacy endpoints included total daily ON time, ON time with no/non-troublesome dyskinesia, Unified Parkinson’s Disease Rating Scale and Parkinson's Disease Questionnaire-39 items. A post-hoc analysis was performed to describe the efficacy of safinamide in both genders on motor symptoms, motor fluctuations and quality of life. 128 (42%) out of 305 patients enrolled were women and 177 (58%) men. Our additional analyses of the XINDI study have shown that safinamide, compared to placebo, was associated with improvements in motor symptoms, motor fluctuations and quality of life in both genders, with some differences in the response that did not reach statistical significance, possibly due to sample size limitation and post-hoc design of the study. The changes from baseline at week 16 were > 50% higher in the females compared to males for the total daily OFF time (− 1.149 h vs − 0.764 h in males), the total daily ON time (1.283 h vs 0.441 h in males), the UPDRS total score (− 8.300 points vs − 5.253 points in males) and the UPDRS part II score (− 2.574 points vs − 1.016 points in males). The changes from baseline at week 16 were higher in the females compared to males in the “ADL” domain (− 6.965 points vs − 5.772 points in males), the “Emotional well-being” domain (− 6.243 points vs − 4.203 in males), the “Stigma” domain (− 6.185 points vs − 4.913 points in males) and the “Bodily discomfort” domain (− 5.196 points vs 1.099 points in males), while were higher in males in the “Mobility” score (− 6.523 points vs − 4.961 points in females) and the “Communication” score (− 3.863 points vs − 1.564 points in females). Safinamide was shown to improve PD symptoms and quality of life in both male and female Chinese patients. Possible differences in the response between genders need to be further studied in larger and different ethnic populations
Efficacy of Safinamide and Gender Differences During Routine Clinical Practice
No full textBackground: There is increasing evidence of gender differences in the epidemiology and clinical manifestation of both motor and non-motor symptoms of Parkinson's disease (PD). Nevertheless, few data are available on gender differences in the response to antiparkinsonian drugs. Safinamide is a multimodal drug with positive effects on motor and non-motor fluctuations that might improve patients' care and quality of life. Objective: To analyze gender differences on clinical effects of safinamide in PD patients treated in real-life conditions during the SYNAPSES trial. Methods: SYNAPSES was a multinational, multicenter, observational study. At baseline, patients with PD diagnosis received safinamide as an add-on to levodopa and were followed up for 12 months, with visits performed every 4 months. A new statistical analysis was performed to describe the efficacy of safinamide in men and women on motor complications, motor symptoms, and adverse events. Results: Six hundred and sixteen (38%) out of 1,610 patients enrolled in the SYNAPSES study were women and 994 (62%) men. Safinamide improved motor symptoms and motor complications (fluctuations and dyskinesia) in both genders, with a good safety profile and without requiring any change in the concomitant dopaminergic therapy. Clinically significant improvements, according to the criteria developed by Shulman et al., were seen in 46% of male and female patients for the UPDRS motor score and 43.5% of men vs. 39.1% of women for the UPDRS total score. Conclusions: Safinamide was effective in improving motor fluctuations and dyskinesia and proved to be safe in both male and female patients with PD. Further prospective studies, specifically addressing potential gender differences in response to PD therapies, are needed to develop tailored management strategies
A novel phenotype in an Italian family with a rare progranulin mutation
No full textIntroduction: Progranulin (PGRN) is a secreted glycoprotein encoded in humans by the GRN gene, located on chromosome 17q21. Several nonsense and missense pathogenetic GRN mutations have been described. Objective: We herein describe two sisters carrying a rare GRN mutation with extremely different clinical features and family history of dementia and behavioral disorders, with a novel presentation with stridor and dysphonia. Methods: Patients underwent a multidimensional assessment including neurological and neuropsychological evaluation, structural and functional imaging, and genetic screening. Results: The younger sister presented at the age of 64 with inspiratory stridor, dysphonia and exercise-induced dyspnea. Transnasal fiberoptic laryngoscopy showed bilateral adduction of the vocal cords at rest and paradoxical further adduction of the vocal cords during forced inspiration, suggesting the hypothesis of an adductor laryngeal dystonia. The older sister presented at the age of 63 with a rapidly progressive corticobasal syndrome. The only clinical feature common to both sisters was a dysexecutive syndrome. The c.893G > A mutation in exon 9 of GRN was found in heterozygosis in both sisters, causing a missense Arginine to Histidine substitution in position 298 of the protein (p.R298H). Conclusions: Our report supports the pathogenicity of the GRN p.R298H mutation, which is first detected in two members from the same family, showing an extremely different phenotypes. Moreover, we report the first case of an FTD-associated mutation presenting with inspiratory stridor and dysphonia linked to adductor laryngeal dystonia, thus expanding the clinical spectrum of GRN-related disorders
New medical and surgical findings in multidisciplinary approach of gorlin-goltz syndrome
No full textObjectives. Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder. The disease shows multiple organ involvement with variable clinical presentation. A multidisciplinary approach is required for its prompt clinical diagnosis and management. The diagnosis of the syndrome was based on its clinical presentation, radiological features and histopathological findings. Methods. This paper highlights a surgical and medical treatment of a case of GGS. A 42-years-old Italian female, affected by GGS, was referred to our surgical department for evaluation of multiple naevoid basal cell epithelioma and recurrent radiolucent jaw lesions. The syndrome was diagnosed based on its clinical presentation, radiological features and histopathological findings. Results. Removal of basal cell carcinomas and enucleation of the jaw cysts along with chemical cauterization with Carnoy’s solution were performed under general anesthesia. In the left side a mandibular resection BRC according to Urken classification was necessary, and a free fibula flap through a minimally invasive technique was harvested for mandibular reconstruction. During follow-up no sign of recurrence was detected, ongoing implant oral rehabilitation. Conclusion. Gorlin-Goltz syndrome (GGS) is a rare disorder. As we describe on the paper the disease shows multiple organ involvement with variable clinical presentation. We suggest a multidisciplinary approach for its prompt clinical diagnosis and management
Sex Differences in Parkinson’s Disease: From Bench to Bedside
No full textBackground: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and gender differences have been described on several aspects of PD. In the present commentary, we aimed to collect and discuss the currently available evidence on gender differences in PD regarding biomarkers, genetic factors, motor and non-motor symptoms, therapeutic management (including pharmacological and surgical treatment) as well as preclinical studies. Methods: A systematic literature review was performed by searching the Pubmed and Scopus databases with the search strings “biomarkers”, “deep brain stimulation”, “female”, “gender”, “genetic”, “levodopa”, “men”, “male”, “motor symptoms”, “non-motor symptoms”, “Parkinson disease”, “sex”, “surgery”, and “women”. Results: The present review confirms the existence of differences between men and women in Parkinson Disease, pointing out new information regarding evidence from animal models, genetic factors, biomarkers, clinical features and pharmacological and surgical treatment. Conclusions: The overall goal is to acquire new informations about sex and gender differences in Parkinson Disease, in order to develop tailored intervetions
Bimaxillary orthognathic surgery with a conventional saw compared with the piezoelectric technique: a longitudinal clinical study
No full textThe only cutting technique used for osteotomies in orthognathic surgery for many years has been a saw, but recently piezoelectric surgery has been introduced as a possible alternative. The aim of this study was to find out if piezoelectric surgery can be more comfortable for patients having orthognathic surgery. A total of 25 patients with dentofacial deformities (seven male and 18 female), were treated from January 2016 to September 2017. In 11 patients, osteotomies were made using a conventional saw, while in 14 a piezoelectric device was used. The variables assessed were: operating time, postoperative swelling, postoperative pain, and cutaneous sensitivity of the upper and lower lips. The duration of operation for the piezosurgery group was significantly longer than that for controls, but the patients had less swelling at all follow-up visits, and the difference was significant at the 30-day follow-up (p = 0.045). Those who had piezosurgery had significantly less pain at the three-day follow up (p = 0.035). There was a significant difference in cutaneous sensitivity only for the right side of the upper lip and only at the one-day follow-up. We conclude that piezoelectric surgery offers some advantages in lessening swelling and the perception of pain after orthognathic surgery, but further investigations are required
Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation
No full textAbstract Background In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m2 weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. Methods 40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m2 to 100 mg/m2. Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients. Results Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine. Conclusion Low-dose fotemustine at 65–75 mg/m2 (induction phase) followed by 75–85 mg/m2 (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p
Intraocular pressure and choroidal thickness postural changes in multiple system atrophy and Parkinson's disease
No full textTo evaluate intraocular pressure (IOP) and choroidal thickness (ChT) postural changes in multiple system atrophy (MSA), Parkinson's disease (PD) patients and healthy controls (HC). 20 MSA patients, 21 PD patients and 14 HC, were examined. All subjects underwent a complete examination, including corneal thickness, ChT, IOP and axial length (AL) measurements. IOP measurement was performed in supine, sitting, and standing positions, whereas ChT in sitting and standing positions. Supine to standing IOP variations were significantly higher in MSA vs PD(p = 0.01) and in MSA vs HC (p < 0.0001), whereas no significant differences were observed between PD and HC (p = 0.397). Mean sub-foveal ChT in MSA was 240 ± 92 μm in sitting position, and 215 ± 94 μm in standing position with a significant reduction (p = 0.008). Mean sub-foveal ChT in PD was 258 ± 79 μm in sitting position, and 259 ± 76 μm in standing position (p = 0.887). In HC it was 244 ± 36 μm in sitting position, and 256 ± 37 μm in standing position with a significant increase (p = 0.007). The significant IOP and ChT postural changes can be considered additional hallmarks of autonomic dysfunction in MSA and further studies are needed to consider them as biomarkers in the differential diagnosis with PD
Open reduction and internal fixation without rigid maxillomandibular fixation: evidence based or merely a surgical dictum? A comparative pilot study on 24 cases
No full textObjective: The objective of the study was to evaluate the results and immediate postoperative complications following open reduction and internal fixation of mandibular fractures with or without postoperative maxillo-mandibular fixation MATERIALS AND METHODS: The study spanned over a period of 24 months, extending from October 2015 to October 2017. The study sample comprised 24 subjects between the age range of 18 to 65 years. They were randomly divided into two groups: Group A included subjects in whom open reduction and internal fixation was followed by maxilla-mandibular fixation for 15 days, and Group B subjects in whom only open reduction and internal fixation was done, followed by immediate mobilization. The outcomes evaluated were swelling, pain, simplified oral hygiene index and occlusion. The subjects were followed for all these outcomes on 1st, 7th and 15th days. The occlusion was assessed for 5 days. Any other intra/post-operative complications were additionally noted. Results: There was no statistical difference between the groups for swelling, pain and occlusion. The patients with postoperative maxilla-mandibular fixation had poorer oral hygiene when compared to the other group (p<0.001). Conclusions: The use of maxilla-mandibular fixation post open reduction and internal fixation seems to offer no additional benefits to the patients. According to the results of the study, this traditional surgical dictum seems to be used by the surgeons due to the lack of any scientific evidence. However, further studies should be conducted to confirm this statement
Energy expenditure, body composition and dietary habits in progressive supranuclear palsy
No full textIntroduction: Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is associated with changes in energy expenditure, body composition and dietary intake compared with Parkinson’s disease and healthy controls; (2) assess the accuracy of the Harris–Benedict equation to predict measured rest energy expenditure in progressive supranuclear palsy; (3) verify differences according to sex, phenotypes, disease severity and presence of dysphagia in progressive supranuclear palsy. Methods: Twenty-one progressive supranuclear palsy, 41 Parkinson’s disease and nine healthy controls were included. Rest energy expenditure was assessed with indirect calorimeter, body composition with bio-impedance analysis and physical activity and dietary intake were estimated with a validated frequency questionnaire. Parametric testing was used to analyze differences between groups. Results: Progressive supranuclear palsy showed reduced total daily energy expenditure and physical activity compared to both other cohorts (p < 0.001) and a tendency toward lower fat-free mass compared to Parkinson’s disease (p > 0.05). Limited accuracy was shown for the Harris–Benedict equation (accurate prediction frequency < 60%). Greater disease severity was associated with lower rest energy expenditure (p = 0.030), fat-free mass (p = 0.026) and muscle mass (p = 0.029). Conclusion: Greater disease severity is associated with reduction in rest energy expenditure likely due to the reduction in lean mass and muscle mass. Such data may pave the way to clinical trials evaluating the efficacy of muscle-targeted nutritional support and physical therapy in preserving muscle mass and improving motor performances in progressive supranuclear palsy at early stages
