Francesco Masedu

Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial

BACKGROUND The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer. METHODS We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174. FINDINGS 124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group. INTERPRETATION Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone. FUNDING None.

The interaction between body position and vibration frequency on acute response to whole body vibration

PURPOSE The present study was designed to investigate the electromyographic (EMG) response in leg muscles to whole-body vibration while using different body positions and vibration frequencies. METHODS Twenty male sport sciences students voluntarily participated in this single-group, repeated-measures study in which EMG data from the vastus lateralis (VL) and the lateral gastrocnemius (LG) were collected over a total of 36 trials for each subject (4 static positions × 9 frequencies). RESULTS We found that vibration frequency, body position and the muscle stimulated had a significant effect (P-values ranged from 0.001 to 0.031) on the EMG response. Similarly, the muscle × frequency and position × muscle interactions were significant (P < 0.001). Interestingly, the frequency × positions interactions were not significant (P > 0.05). CONCLUSIONS Our results indicate that lower frequencies of vibration (25-35 Hz) result in maximal activation of LG, whereas higher frequencies (45-55 Hz) elicit the highest responses in the VL. In addition, the position P2 (half squat position with the heels raised) is beneficial both for VL and LG, independently of the vibration frequency.

Affective and cognitive empathy in adolescents with autism spectrum disorder

The broad construct of empathy incorporates both cognitive and affective dimensions. Recent evidence suggests that the subjects with autistic spectrum disorder (ASD) show a significant impairment in empathic ability. The aim of this study was to evaluate the cognitive and affective components of empathy in adolescents with ASD compared to controls. Fifteen adolescents with ASD and 15 controls underwent paper and pencil measures and a computerized Multifaceted Empathy Test. All measures were divided into mentalizing and experience sharing abilities. Adolescents with ASD compared to controls showed deficits in all mentalizing measures: they were incapable of interpreting and understanding the mental and emotional states of other people. Instead, in the sharing experience measures, the adolescents with ASD were able to empathize with the emotional experience of other people when they express emotions with positive valence, but were not able to do so when the emotional valence is negative. These results were confirmed by the computerized task. In conclusion, our results suggest that adolescents with ASD show a difficulty in cognitive empathy, whereas the deficit in affective empathy is specific for the negative emotional valence.

Adult-onset Still’s disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

BackgroundAdult-onset Still’s disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients.MethodsThis study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed.ResultsOne hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of ≥ 7.0 was reported.ConclusionsOur study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death.

Prognostic factors of macrophage activation syndrome, at the time of diagnosis, in adult patients affected by autoimmune disease: Analysis of 41 cases collected in 2 rheumatologic centers.

Macrophage activation syndrome (MAS) is a rare, life-threatening disease in which early diagnosis and aggressive therapeutic strategy may improve the outcome. Due to its rarity, epidemiologic data are still lacking. Hyperferritinemia is frequently associated with MAS and might modulate the cytokine storm, which is involved in the development of multiple organ failure. In this paper, we investigated clinical data, treatments, and outcome of a homogeneous cohort of 41 adult MAS patients, complicating autoimmune rheumatic diseases. MAS-related death occurred in 17 patients (42.5%) during the follow-up, and older age and increased serum ferritin levels, at the time of diagnosis, were significantly associated with mortality. In conclusion, adult MAS is associated with high mortality rate. Some clinical features at diagnosis may be predictive of MAS-associated death.

Sleep Disturbances in Patients With Advanced Cancer in Different Palliative Care Settings.

CONTEXT Information regarding sleep disturbances in the population with advanced cancer is meager. OBJECTIVES To assess the prevalence of sleep disturbances and possible correlations with associated factors in a large number of patients with advanced cancer admitted to different palliative care settings. METHODS This was an observational study performed in different settings of palliative care. A consecutive sample of patients with advanced cancer was prospectively assessed for a period of six months. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System scores, and concomitant medical treatment were recorded. Patients were administered the Athens Insomnia Scale and the Hospital Anxiety and Depression Scale (HADS). RESULTS A total of 820 patients were surveyed. Mean age was 69.7 years (SD 12.7), and 429 patients were males. Consistent sleep disturbances (moderate to maximum) were found in 60.8% of patients. Aged patients were less likely to have sleep disturbances, whereas a poor Karnofsky level was significantly associated with sleep problems. Breast, gastrointestinal, head and neck, lung, and prostate cancers were associated with sleep problems. Patients who had a secondary school or undergraduate education had less sleep disturbances. Hormone therapy and use of opioids and corticosteroids were positively associated with sleep disturbances, and there was a positive correlation of HADS-Anxiety and HADS-Depression scores with sleep disturbances. CONCLUSION More than 60% of palliative care patients have relevant sleep disturbances. Several factors associated with sleep disorders have been identified and should prompt physicians to make a careful examination and subsequent treatment of these disturbances.

Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

Objectives Several studies showed the close relationship between Rheumatoid Arthritis (RA) and cerebro-cardiovascular events (CVEs) and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV) and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis. Methods We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis. Results We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH), type 2 diabetes mellitus and metabolic syndrome (MS), at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis. Conclusions Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

The EMG activity-acceleration relationship to quantify the optimal vibration load when applying synchronous whole-body vibration.

PURPOSE To date are lacking methodological approaches to individualizing whole-body vibration (WBV) intensity. The aim of this study was: (1) to determine the surface-electromyography-root-mean-square (sEMG(RMS))-acceleration load relationship in the vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF), lateral gastrocnemius (LG) muscles during synchronous WBV, and (2) to assess the reliability of the acceleration corresponding to the maximal sEMG(RMS). METHODS Twenty-five sportsman voluntarily took part in this study with a single-group, repeated-measures design. All subjects postured themselves in an isometric half-squat during nine trials in the following conditions: no vibrations and random vibrations of different acceleration loads (from 0.12 to 5.72 g). RESULTS The sEMG(RMS) were dependent on the acceleration loads in the VL (p = 0.0001), LG (p = 0.0001) and VM (p = 0.011) muscles; while RF was not affected by the acceleration loads (p = 0.508). The comparisons among the sEMG(RMS)-accelerations relationships revealed a significant difference between the LG and the others muscles (p = 0.001). No significant difference was found between the different thigh muscles (p > 0.05). The intra-class correlation coefficient ranged from 0.87 to 0.99 for the measurements performed on the LG, VL and VM. CONCLUSIONS The sEMG(RMS)-acceleration relationship in the VL, VM and LG is a reliable test to individualize the WBV intervention.

The Role of Theory of Mind on Social Information Processing in Children With Autism Spectrum Disorders: A Mediation Analysis

Individuals with autism spectrum disorders (ASD) show significant impairments in social skills and theory of mind (ToM). The aim of this study was to evaluate ToM and social information processing abilities in 52 children with ASD compared to 55 typically developing (TD) children. A mediation analysis evaluated whether social information processing abilities can be mediated by ToM competences. In our results, children with autism showed a deficit in social skills and ToM components. The innovative results of our study applying mediation analysis demonstrate that ToM plays a key role in the development of social abilities, and the lack of ToM competences in children with autism impairs their competent social behavior.

MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: A pilot study

Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status. The metastatic tissues of 27 stage III melanoma patients with locoregional metastases located in the pelvis subjected to melphalan hypoxic pelvic perfusion were examined. The methylation status of the MGMT promoter was investigated by MS-MLPA probes analysis and the presence of the BRAF V600E mutation was analyzed by CAST-PCR. The median survival times were estimated using the Kaplan–Meier curves and were stratified according to the clinicopathological characteristics of patients and lesions. The overall median survival time was 17 months. The 1-year, 3-year, and 5-year survival rates were 66.7, 18.5, and 7.4%, respectively. Disease stage, burden, and percentage of MGMT methylation significantly affected survival. We estimated an MGMT promoter methylation cut-off of at least 14%, which was significantly associated with a longer survival after melphalan regional chemotherapy. Our data suggest that MGMT promoter methylation could be an important factor in determining which melanoma patients should receive melphalan regional chemotherapy, but its prognostic significance in the routine clinical setting needs to be clarified in a larger study.