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Meningiomas are usually considered benign lesions, however a proportion of them shows a more aggressive behavior, defined high-grade meningiomas (HGM). Effective medical treatments are lacking, especially at the time of recurrence. Through a retrospective analysis, we examined epidemiological, diagnostic, therapeutic, recurrence information and survival data of HGM treated at our institution between 2010 and 2018. 183 patients (105 females and 78 males), with median age of 58 years (25–88), were included; 168 were atypical, 12 anaplastic, 3 rhabdoid. Overall, m-PFS was 4.2 years, and m-OS was 10.3 years. Gross-total resection had a 5-year survival rate of 95% compared with subtotal/partial resection (86% and 67%) (p = 0.002). Higher expression of Ki-67/MIB-1 seems associated with higher risk of death (HR:1.06 with 95% CI, 1.00–1.12, p = 0.03). No statistically significant differences were seen in survival between the group managed with a wait-and-see strategy vs the group treated with RT while a difference on PFS was seen (4.1 years vs 5.2 years p = 0.03). After second recurrence, the most employed treatments were systemic therapies with a very limited effect on disease control. Data confirmed the aggressive behavior of HGM. The extent of resection seems to correlate with a favorable outcome regardless histological subtypes. The role of RT remains controversial, with no statistically significant impact on OS but a possible role on PFS. Recurrent HGM remains the real challenge, to date no chemotherapies are able to achieve disease control. Future research should focus on biological/molecular predictors in order to achieve a patient-tailored treatment. •Aggressive behavior of HGM.•The extent of resection seems to correlate with a favorable outcome regardless histological subtypes.•The role of RT remains controversial, with no statistically significant impact on OS but a possible role on PFS.•Recurrent HGM remains the real challenge, to date no chemotherapies are able to achieve disease control.•Future research should focus on biological/molecular predictors in order to achieve a patient-tailored treatment.

MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally, both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features (no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging (DWI) and spectroscopy. All the gliomas had histopathological diagnoses. Sensitivity and specificity of cMRI pre-operative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when aMRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV <1.46 and minimum rADC >1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of aMRI to differentiate between LGG and HGG and to predict survival improved as the number of aMRI techniques considered increased. In a selected population of suspected LGG, classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade.

Background The incidence of glioblastoma (GBM) in the elderly population is currently increasing, with a peak seen between 65 and 84 years. The optimal treatment in terms of both efficacy and quality of life still remains a relevant and debated issue today. The purpose of our study was to evaluate the feasibility of short-course hypofractionated accelerated radiotherapy (HART) in GBM patients aged over 70 years and with a good Karnofsky performance score (KPS). Methods A review of medical records at the “Istituto Neurologico C. Besta” was undertaken; patients aged ≥ 70 years who had undergone adjuvant HART for GBM between January 2000 and January 2004 were included in the study. HART was administered to a total dose of 45 Gy, 2.5 Gy/fraction, in three daily fractions for three consecutive days/cycle fractions each, delivered in two cycles (split 15 days). Results A total of 33 patients were evaluable for the current analysis. Median follow-up was 10 months. According to CTCAE (version 3.0) criteria, none of the patients developed radiation-induced neurological status deterioration or necrosis. KPS evaluation after HART was found to be stable in 73 % of patients, improved in 24 %, and worse in 3 %. The median overall survival time of the entire study population was 8 months (range 2–24). Conclusions Our findings suggest that a hypofractionated accelerated schedule can be a safe and effective option in the treatment of GBM in the elderly.

Background Epidemiological studies on the association between allergic disorders, T-helper type 2 (Th2) mediated, and multiple sclerosis (MS), a T-helper type 1 (Th1)/Th17-mediated disease, provided conflicting results. Objective The aim of this study was to further examine the association between allergic disorders and MS. Methods The association between MS and previous medical history of any type of allergy has been investigated in a population-based case-control study conducted in Northern Italy, based on telephone interviews to 423 cases and 643 population controls (refusal rates 3.7% and 9.4%, respectively). Controls were a random sample of the general population. Results A history of atopic allergies seems to confer protection against MS (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.38–0.89; P = 0.012). In particular, the prevalence of allergic asthma was 4.9% in people with MS and 12% in control subjects (OR = 0.38; 95% CI 0.22–0.66, P < 0.01). No association was found between MS and nonatopic allergies. Conclusions Our findings are confirmatory of the putative protective effect of Th2-mediated disorders on Th1 immune responses associated with MS. A unifying theory on the mechanisms by which previous history of atopic allergies may modify the risk of MS is still lacking.

OBJECTIVES Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8.5). Patients’ participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patientsv 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

The role of parental occupational exposure in childhood brain tumors was investigated in a population-based case-control study grouping 251 cases and 601 controls from three European centers: Milan (Italy), Paris (France), and Valencia (Spain). Parental occupational exposure to solvents and polycyclic aromatic hydrocarbons (PAH) during the five-year period before birth was estimated using a job-exposure matrix developed earlier in the same countries. Odds ratios (OR) of brain tumors for each occupation and occupational exposure were estimated by logistic regression, adjusting for child's age, gender, exposure to tobacco smoke and ionizing radiation, mother's age and years of schooling, and center. The risk of childhood brain tumors rose when fathers worked in agriculture (OR = 2.2, 95 percent confidence interval [CI] = 1.0-4.7) and motor-vehicle-related occupations. In the latter group, the risk increased for primitive neuroectodermal tumors in particular (OR = 2.7, CI = 1.1-6.6). Astroglial tumors were more frequent among children of mothers in health services (OR = 2.2, CI = 1.0-4.9). Paternal exposure to PAHs was associated with an increased, but not dose-related, risk of primitive neuroectodermal tumors (OR = 2.0, CI = 1.0-4.0), and maternal exposure to solvents at a high level was associated with an increased risk of both astroglial (OR = 2.3, CI = 0.9-5.8) and primitive neuroectodermal tumors (OR = 3.2, CI = 1.0-10.3).

We performed a qualitative study to investigate the experiences of participants in a multicentre randomized controlled trial on a home-based palliative approach (HPA) for adults with severe multiple sclerosis (MS) and their caregivers. Our aim was to explore the strengths and challenges of the intervention, and circumstances that may have influenced its efficacy. Participants to the qualitative study were the patients, their caregivers, patient referring physicians, and the teams who delivered the HPA intervention. We performed semi-structured one-on-one interviews with 12 patients and 15 informal caregivers chosen using a maximum variation strategy, two focus group meetings with patient referring physicians (4 participants each), and one with the HPA teams (9 participants). From data analysis (framework method) 38 sub-categories emerged, which were grouped into 10 categories and 3 themes: 'expectations,' 'met and unmet needs', and 'barriers'. Intervention benefits were improved control of symptoms and reduced sense of isolation of the patient-caregiver dyads. Limitations were: factors related to experimental design (difficulty of dyads in identifying examiner and team roles, additional burden for caregivers); team issues (insufficient team building /supervision, competing priorities); limitations of the intervention itself (insufficient length, lack of rehabilitation input); and external factors (resource limitations, under-responsive services/professionals). The referring physician focus groups provided little experiential data. The HPA reduced patient symptoms and sense of isolation in patients and caregivers. The indirect role of the HPA teams, and insufficient length of the intervention were key limitations. The experimental design imposed additional burdens on the dyads. Key barriers were the paucity of available services, the demanding administrative procedures, and lack of networking facilities. These findings suggest that two major requirements are necessary for home palliative care to be effective in this patient population: HPA teams well-connected with MS rehabilitation services, and care delivered over the long-term, with variable intensity. Current Controlled Trials ISRCTN73082124 (Registered 19/06/2014).

Aim The aim of this study was to describe the changes in quality of life and in levels of anxiety and depression experienced by caregivers of patients with brain tumour 18 months after their bereavement. Methods This longitudinal study employed data from two time points: time 1, during the hospital stay of the caregiver's loved one; and time 2, approximately 18 months after the death of the patient. A total of 51 caregivers agreed to participate in the study at both time points. We used the Hospital Anxiety and Depression Scale and the 36-Item Short Form Health Survey; we compared the data obtained at the two time points using the paired-samples t-test. Results Caring for someone with a brain tumour had a greater impact on the caregivers’ mental health than on their physical well-being. At time 2, the caregivers’ levels of anxiety and depression and psychological burden were decreased, indicating that they were in a better emotional state than they had been in time 1. However, the mean values in the depression, vitality, and mental health subscales were lower than those in the normative data, indicating that these caregivers had a worse psychological status than members of the normative group. Conclusion Our study underscores the necessity of supporting caregivers and monitoring their suffering levels; such suffering can compromise their social and work lives, not only during the disease trajectory but also in bereavement. Providing psychological and emotional support for caregivers of patients with brain tumour during both periods could lessen the suffering and unhappiness of these caregivers.

We devised a treatment protocol for anaplastic gliomas consisting of:(a) chemotherapy prior to radiotherapy (b) a second chemotherapy regimen at tumor recurrence (c) repeated surgery whenever possible. 41 Anaplastic Astrocytoma (AA), 16 Anaplastic oligoastrocytoma (AOA) and 14 anaplastic oligodendroglioma (AOD) patients were treated. After surgery all patients received 5-6 cycles of carmustine+Cisplatinum chemotherapy. Radiotherapy was started during the last 2-3 cycles of chemotherapy. 17 patients (30.5%) were reoperated on at recurrence. All recurring patients underwent PVC chemotherapy. At this moment disease recurred in 56 patients. Median TTP was 24.5, 38.7 and 58.2 months for AA, AOA and AOD respectively. Median ST was 38.8, 71.8 and 73 months. In conclusion our sandwich protocol of prior chemotherapy, overlapping irradiation with second chemotherapy and, in favourable cases, a second surgical intervention, is of benefit in patients with anaplastic gliomas.