Search

To evaluate the effects of rehabilitation (physical and cognitive) treatments on the diagnosis severity and Disability Rating Scale (DRS) scores, adjusted for a number of potential confounders measured at baseline, in a large cohort of patients with disorders of consciousness across time.An observational, longitudinal (2 evaluations), multicenter project was made in 90 Italian centers.Patients (N=364) with a diagnosis of disorders of consciousness.Primary outcome was the severity of diagnosis, expressed on an ordinal scale (OtherMCSVSdeath). In the Other group were included patients who emerged from an MCS and recovered consciousness. The secondary outcome was the DRS score (range of 0-30 with 30 being the worst value). The DRS is a tool used to define the level of residual disability, commonly used to classify the level of functional impairment in patients with acquired brain injury. Both outcomes were measured for each wave.A total of 364 subjects having a complete set of demographic, clinical, and pharmacologic data were included in the propensity score (PS) analysis. Results showed that the rehabilitation treatments (physical and cognitive) reduced the clinical worsening over time in both severity diagnosis and DRS (around 6.5 points) in patients with disorders of consciousness across different propensity score strategies (ie, PS matching, PS adjustment, and PS-weighted procedures). In addition, cognitive protocols seem to be limited to patients with a median value of DRS=23.Our propensity score analysis suggests that rehabilitation treatment protocols seem effective and should be applied to a broader spectrum of patients with disorders of consciousness.

Importance: Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. Objective: To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). Design, setting, and participants: This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. Exposures: Upfront PRRT or upfront chemotherapy or targeted therapy. Main outcomes and measures: The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. Results: Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P

Background: Glioblastoma multiforme (GBM) is a rare and deadly disease, with a reported average incidence rate of 3.19 cases per 100,000 inhabitants. Fotemustine, a third-generation nitrosourea with an alanine phosphor carrier that facilitates cellular penetration, has been extensively investigated in the setting of recurrent/progressive disease after initial treatment. Fotemustine is usually administered following a schedule consisting of 3 doses every week, followed by maintenance doses administered every 3 weeks. Methods: In this phase I/II trial, we aimed to assess whether the use of a biweekly regimen allowed administration of higher dose than the standard 100mg/m2 dose approved per label indication in a population of patients with recurrent GBM. In this phase I/II trial, fotemustine was administered intravenously over 1hour every 2 weeks at either 120 or 140mg/m2 doses for up to 1 year, until disease progression, unacceptable toxicity, or patient's request to withdraw from the study. The phase I part of the trial was conducted following the classic 3+3 study design. The phase II part of the trial was a single-arm study. The primary efficacy endpoint was the percentage of patients who had not progressed after 24 weeks (PFS-24). Results: Thirty-seven patients were enrolled in this phase I/II trial from August 2006 to November 2011. Treatment was well tolerated in the overall population. Main severe toxicity was grades 3 and 4 thrombocytopenia, which occurred in 4 of 6 patients treated at the 140mg/m2 dose level and in 3 of 31 patients treated at 120mg/m2. Median PFS and overall survival were 12.1 (1-40.2) weeks and 19.7 (1-102) weeks, respectively. Conclusion: We conclude that fotemustine can be safely administered at 120mg/m2 biweekly. The efficacy of such modified schedule and doses should be compared to the biweekly schedule at 80mg 2 and the standard weekly schedule at 80 to 100mg/m2.

Background Literature shows that occurrence of comorbidities in people with severe acquired brain injury (sABI) is a common problem in rehabilitation stay. Consequently, patients could require an increase of interventions for diagnosis and treatment of clinical conditions, with a reduction of the rehabilitative take in charge for both clinical and organizational aspects. Aim The first aim was to evaluate the rate of clinical conditions of sABI patients at admission in rehabilitation and the types of rehabilitative interventions performed in the first week; second objective was to explore the impact of clinical conditions on real rehabilitative take in charge. Design Cross sectional study. Setting Inpatient rehabilitation centers. Population The study included data from 586 sABI patients. Methods Collected data regarded anamnestic information, functional status assessed by means of Glasgow Outcome Scale, Levels of cognitive functioning, Early Rehabilitation Barthel Index, comorbidities at admission and type of rehabilitative interventions carried out in first week of rehabilitation stay. Spearman correlation coefficients were applied to detect possible correlations between the number of treatments in first week and clinical variables; through a multiple regression analysis the effect of patient's characteristics on rehabilitative take in charge was explored. Results Data from the sABI patients: mean age 55.1±17.1 years; etiology of sABI was vascular in 315 patients (53.8%), anoxic in 83 (14.2%), neoplastic in 17 (2.9%), infectious in 15 (2.6%), traumatic in 150 (25.6%); 6 subjects (1%) presented a mixed etiology. Need of cardiorespiratory monitoring, pressure sores, infections or presence of multi drug resistant bacteria were the most frequent comorbidities. Passive mobilization, sitting positioning, arousal/awareness stimulation, evaluation and management of dysphagia were the interventions most frequently carried out in the first week. The regression analysis showed that severe neurological and clinical conditions, acute organ failure, cardio-respiratory instability and paroxysmal sympathetic hyperactivity significantly limit access to rehabilitative sessions. Conclusions In sABI patients clinical comorbidities requiring elevated care assistance are frequent at admission in rehabilitation from acute wards and may interfere with rehabilitative take in charge. Clinical rehabilitation impact The knowledge of clinical complexity of sABI patients may improve their care pathways, promoting early and appropriate transition from acute care to rehabilitation settings.

Typical (TC) and atypical (AC) carcinoids are low-grade neuroendocrine tumors (NETs) of the lung and, are neglected diseases in respect of both high-grade NETs of the lung (i.e. small-cell lung cancer and large-cell neuroendocrine carcinoma) and gastroenteropancreatic (GEP)-NETs. AC and TC account for 2 and 0.2% of all thoracic malignancies, respectively, and have a 12.9% chance of metastatic spread at diagnosis, reaching up to 20% during disease history. There are very few trials specifically designed for lung NETs, and therapeutic options are mainly derived by studies carried out in patients with GEP-NETs. We report a case of a patient affected by AC progressed to available standard treatments who received off-label treatment with sunitinib, a well-known multitarget tyrosine-kinase inhibitor with marked antiangiogenic activity, used routinely for the treatment of GEP-NETs. During treatment, the patient required the administration of an alternative schedule to improve tolerability, with benefit, and achieved a partial response according to the RECIST criteria, which is unusual in NETs. We critically reviewed available data supporting the use of somatostatin analogs, chemotherapy, and target therapies (everolimus and sunitinib) in advanced lung NETs. In the review, ongoing trials in lung NETs and future developments in this research field are also discussed.

We explored how internet use could preclude or increase young people’s in-person leisure activities and also explored how the relationship between internet use and leisure activities could vary by considering different sources of heterogeneity. We first investigated the internet use-leisure activities relationship globally estimating each as a single construct, and we then decomposed the indicators of both constructs in groups according to their nature, taking into account the different components of internet use and leisure activities. Our results suggest that the relationship is positive and stable. However, differences were identified once we considered the nature of the activities.

Background Gastric neuroendocrine neoplasias (gNEN) are defined as type I if associated with atrophic body gastritis and type III when tumour is sporadic. This classification, together with grading and size, plays a crucial prognostic role. Nevertheless, the impact of these features on clinical outcome is not clear. Aim To identify factors predicting poor outcome. Patients and methods Analysis of type I and type III gNEN. A composite endpoint was defined if tumour-related death or metastases or angioinvasion were observed. Results 156 gNENs were evaluated: 137 (87.8%) type I and 19 (12.2%) type III. Among type I, 103 were G1 (75.2%) and 34 (24.8%) were G2. In type III group, 8 were G1 (42.1%), 10 were G2 (52.6%), and 1 was G3 (5.3%). Negative endpoint occurred in 18 patients including 10 type III and 8 type I. Male gender (p = 0.032), tumour type (p = 0.003) and size >10 mm (p = 0.024) were predictors for poor outcome, whereas Ki67 was not confirmed on multivariate analysis (p = 0.192). 5-yr survival rates in type I and type III were 100% and 76.2%, respectively (p = 0.0002). Conclusions Tumour size, tumour type and gender affect clinical outcome in gNENs. In contrast to NENs rising from other sites, Ki67 plays a less important role.