Center for Neuro-Oncology in Turin (Italy):

The Center for Neuro-Oncology of the University Hospital in Turin is hosted by the Division of Neuro-Oncology/Neurology and coordinates the Multidisciplinary Brain Tumor Board (MTB; which includes ..

Glioblastoma in the Elderly: Review of Molecular and Therapeutic Aspects

Glioblastoma (GBM) is the most aggressive primary brain tumour. As GBM incidence is associated with age, elderly people represent a consistent subgroup of patients. Elderly people with GBM show dismal prognosis (about 6 months) and limited response to treatments. Age is a negative prognostic factor, which correlates with clinical frailty, poorer tolerability to surgery or adjuvant radio-chemotherapy, and higher occurrence of comorbidities and/or secondary complications. The aim of this paper is to review the clinical and molecular characteristics, current therapeutic options, and prognostic factors of elderly patients with GBM

The Clinical Impact of the Pulmonary Embolism Severity Index on the Length of Hospital Stay of Patients with Pulmonary Embolism: A Randomized Controlled Trial.

BACKGROUND The Pulmonary Embolism Severity Index (PESI) is an extensively validated prognostic score, but impact analyses of the PESI on management strategies, outcomes and health care costs are lacking. Our aim was to assess whether the adoption of the PESI for patients admitted to an internal medicine ward has the potential to safely reduce the length of hospital stay (LOS). METHODS We carried out a multicenter randomized controlled trial, enrolling consecutive adult outpatients diagnosed with acute PE and admitted to an internal medicine ward. Within 48 h after diagnosis, the treating physicians were randomized, for every patient, to calculate and report the PESI in the clinical record form on top of the standard of care (experimental arm) or to continue routine clinical practice (standard of care). The ClinicalTrials.gov identifier is NCT03002467. RESULTS This study was prematurely stopped due to slow recruitment. A total of 118 patients were enrolled at six internal medicine units from 2016 to 2019. The treating physicians were randomized to the use of the PESI for 59 patients or to the standard of care for 59 patients. No difference in the median LOS was found between the experimental arm (8, IQR 6-12) and the standard-of-care arm (8, IQR 6-12) (p = 0.63). A pre-specified secondary analysis showed that the LOS was significantly shorter among the patients who were treated with DOACs (median of 8 days, IQR 5-11) compared to VKAs or heparin (median of 9 days, IQR 7-12) (p = 0.04). CONCLUSIONS The formal calculation of the PESI in the patients already admitted to internal medicine units did not impact the length of hospital stay

Elderly Gliobastoma Patients: The Impact of Surgery and Adjuvant Treatments on Survival. A Single Institution Experience

Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, and outcome, along with the impact of comorbidities and clinical status on survival. Patients and Methods. We included patients ≥ 65-year-old. We collected information about clinical and molecular features, extent of resection, adjuvant treatments, treatment-related complications, and outcome. Results. We included 135 patients. Median age was 71 years. In total, 127 patients (94.0%) had a Karnofsky Performance Status (KPS) ≥70 and 61/135 (45.2%) a Charlson Comorbidity Score (CCI) > 3. MGMTp methylation was found in 70/135 (51.9%). Subtotal resections (STRs), gross-total resections (GTRs), and biopsies were 102 (75.6%), 10 (7.4%) and 23 (17.0%), respectively. Median progression-free survival and overall survival (mOS) were 8.0 and 10.5 months for the whole cohort. Notably, GTR and radio-chemotherapy with temozolomide in patients with MGMTp methylation were associated with significantly longer mOS (32.8 and 44.8 months, respectively). In a multivariable analysis, risk of death was affected by STR vs. GTR (HR 2.8, p = 0.002), MGMTp methylation (HR 0.55, p = 0.007), and KPS at baseline ≥70 (HR 0.43, p = 0.031). Conversely, CCI and post-surgical complications were not significant. Conclusions. Elderly GBM patients often have a dismal prognosis. However, it is possible to identify a subgroup with favourable clinical and molecular features, who benefit from GTR and radio-chemotherapy with temozolomide. A comprehensive prognostic score is needed to guide treatment modality and predict the outcome

characterization of pm1 bound metallic elements in the ambient air at a high mountain site in northern china

n/

Center for Neuro-Oncology in Turin (Italy)

The Center for Neuro-Oncology of the University Hospital in Turin is hosted by the Division of Neuro-Oncology/Neurology and coordinates the Multidisciplinary Brain Tumor Board (MTB; which includes neuro-oncologists, neurosurgeons, neuroradiologists, neuropathologists, medical and radiation oncologists, and hematologists). The MTB guarantees the continuity of care from diagnosis to the end of life support. The Division of Neuro-Oncology/Neurology has an in- and outpatient clinic. In addition to daily clinical practice, major activities consist of clinical trials, translational studies, and teaching. This neurology-centered model of brain tumor care is similar to other brain tumor centers in the United States and Europe

Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program

Background: Leptomeningeal metastasis is a neurological complication from HER2-positive breast cancer with a poor prognosis and limited treatment options. This study has evaluated the activity of neratinib in association with capecitabine in 10 patients with LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab-based therapy, within a compassionate program, and a comparison was made with a historical control group of 10 patients. Methods: Patients aged ≥ 18 years with histological diagnosis of primary HER2-positive BC, either amplified or mutated, and newly-diagnosed LM were enrolled. Coexistence of BM that has or has not received radiotherapy, as well as prior chemotherapy, hormone therapy, or monoclonal HER2-targeting antibodies or antibody–drug conjugates, were allowed, with the exclusion of lapatinib. Results: Six-months OS was 60% with a median OS of 10 months (95% CI: 2.00–17.0). Three-month intracranial PFS was 60% with a median intracranial PFS of 4.0 months (95% CI: 2.00–6.0). The neurological benefit was observed in 70% of patients with a median duration of neurological response of 6.5 months. The best radiological response was stable disease in 60% of patients. Conclusions: This small series shows that the combination of neratinib and capecitabine is a safe treatment in LM from heavily pretreated HER2-positive BC with clinical efficacy in some patients and is worth investigating in a larger study

Underweight subjects with anorexia nervosa have an enhanced salivary cortisol response not seen in weight restored subjects with anorexia nervosa

The cortisol response to awakening (CAR) has been reported to be enhanced in symptomatic patients with anorexia nervosa (AN). However, it has been not established whether the dysregulation of CAR was a primary phenomenon or a change secondary to malnutrition. Therefore, we aimed to explore the salivary CAR in both underweight and weigh-restored women with AN. Fifty-nine women volunteered for the study. They were 18 underweight AN women, 15 weight-restored AN women and 26 normal-weight healthy women. Saliva samples were collected in the morning, immediately on awakening and after 15, 30 and 60 min to measure saliva levels of cortisol. Participants' anxiety levels in the morning of sampling were measured by the State-Trait Anxiety Inventory. As compared to control women, underweight AN patients showed an enhanced CAR whereas weight-restored patients had a normal CAR. These results could be not explained by group differences in body mass index or levels of anxiety. These findings show, for the first time, that the enhanced CAR occurring in the acute phase of AN is not seen in weight-recovered patients, suggesting that the dysregulated activity of the hypothalamus-pituitary-adrenal axis of symptomatic AN patients is a state-dependent phenomenon

Clinical Significance of Molecular Alterations and Systemic Therapy for Meningiomas: Where Do We Stand?

Meningiomas are common intracranial tumors that can be treated successfully in most cases with surgical resection and/or adjuvant radiotherapy. However, approximately 20% of patients show an aggressive clinical course with tumor recurrence or progressive disease, resulting in significant morbidity and increased mortality. Despite several studies that have investigated different cytotoxic agents in aggressive meningiomas in the past several years, limited evidence of efficacy and clinical benefit has been reported thus far. Novel molecular alterations have been linked to a particular clinicopathological phenotype and have been correlated with grading, location, and prognosis of meningiomas. In this regard, SMO, AKT, and PIK3CA mutations are typical of anterior skull base meningiomas, whereas KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD, and BAP1 correlate with poor outcomes. Moreover, some actionable mutations, including SMO, AKT1, and PIK3CA, regulate meningioma growth and are under investigation in clinical trials. PD-L1 and/or M2 macrophage expression in the microenvironment provides evidence for the investigation of immunotherapy in progressive meningiomas