Dissecting the prognostic signature of patients with astrocytoma isocitrate dehydrogenase-mutant grade 4: a large multicenter, retrospective study.

BACKGROUND: The World Health Organization (WHO) 2021 classification of central nervous system (CNS) tumors classified astrocytoma isocitrate dehydrogenase-mutant (A IDHm) with either microvascular proliferation and/or necrosis or homozygous deletion of CDKN2A/B as CNS grade 4 (CNS WHO G4), introducing a distinct entity and posing new challenges to physicians for appropriate management and prognostication. PATIENTS AND METHODS: We retrospectively collected information about patients diagnosed with A IDHm CNS WHO G4 at three reference neuro-oncological Italian centers and correlated them with survival. RESULTS: A total of 133 patients were included. Patients were young (median age 41 years) and most received post-operative treatment including chemo-radiation (n = 101) and/or temozolomide maintenance (n = 112). With a median follow-up of 51 months, the median overall survival (mOS) was 31.2 months, with a 5-year survival probability of 26%. In the univariate analysis, complete resection (mOS: 40.2 versus 26.3 months, P = 0.03), methyl-guaninemethyltransferase (MGMT) promoter methylation (mOS: 40.7 versus 18 months, P = 0.0136), and absence of telomerase reverse transcriptase (TERT) promoter mutation (mOS: 40.7 versus 18 months, P = 0.0003) correlated with better prognosis. In the multivariate models, lack of TERT promoter mutation [hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.07-0.82, P = 0.024] and MGMT methylation (HR 0.40, 95% CI 0.20-0.81, P = 0.01) remained associated with improved survival. CONCLUSIONS: This is the largest experience in Western countries exploring the prognostic signature of patients with A IDHm CNS G4. Our results show that MGMT promoter methylation and TERT promoter mutation may impact clinical outcomes. This may support physicians in prognostication, clinical management, and design of future studies of this distinct diagnostic entity.

Treatment-emergent central sleep apnoea after surgery for obstructive sleep apnoea.

Central sleep apnoea (CSA) is a lack of drive to breathe during sleep, which can occur in physiologic as well as in pathologic conditions. A particular type of CSA, defined treatment-emergent CSA (TECSA), may occur after the treatment of obstructive sleep apnoea syndrome (OSAS), either with CPAP or surgery. TECSA is transitory and seems to be related to the severity of OSAS. We describe a 51-year-old man affected by severe OSAS who developed severe, transient CSA immediately after upper airways surgery. We believe that CSA was triggered by the sudden variation in nocturnal arterial PCO2, which decreased from 52.3 mmHg before surgery to 42.0 mmHg after surgery. It is conceivable that, due to long-lasting severe OSAS, our patient lowered his chemosensitivity to PCO2. Consequently, the resolution of obstructive apnoeas and the restoration of normal nocturnal values of PCO2 may have reduced the nocturnal PCO2 to the point of being inadequate to stimulate ventilation.

Hyoid myotomy without suspension: a surgical approach to obstructive sleep apnoea syndrome.

The aim of this study was to verify if hyoid myotomy without hyoid suspension is effective in surgical treatment of obstructive sleep apnoea syndrome (OSAS). We recruited six patients with OSAS, aged between 34 to 60 years, with retropalatal and retrolingual upper airway obstruction, non-obese (BMI < 27) and non-compliant to continuous positive airway pressure therapy. Pre-surgical clinical and instrumental evaluations included clinical examination, cephalometry, polysomnography (PSG) and sleep endoscopy. Surgical treatment included nasal surgery, uvulopalatopharyngoplasty, tonsillectomy and hyoid myotomy without hyoid suspension. Follow-up evaluations were performed with serial PSGs, performed early (one week after surgery), and at 1, 6 and 18 months after surgery. We observed that surgery was followed by immediate normalisation of breathing parameters evaluated by PSG that persisted after 18 months. Thus, hyoid myotomy without suspension combined with nasal and palatal surgery may be considered a valid treatment of non-obese OSAS patients with retrolingual and retropalatal collapse. Furthermore, we suggest that hyoid bone suspension, binding it to mandibular or to thyroid cartilage, might be unnecessary in selected cases.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

PURPOSE: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. RESULTS: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. CONCLUSIONS: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

Psychological functioning measures in patients with primary insomnia and sleep state misperception.

OBJECTIVE: Sleep state misperception (SSM) is a term used in the International Classification of Sleep Disorders to indicate people who mistakenly perceive their sleep as wakefulness. SSM is a form of primary insomnia. The aim of this study was to record psychological functioning measures (anxiety, depression, ability to feel pleasure, obsessive-compulsive traits) in a population of patients with primary insomnia and to evaluate the relationship between these measures and the patients' perception of their sleep. MATERIALS AND METHODS: Seventy-six consecutive patients with primary insomnia were enrolled: 34 men and 42 women, mean age 53.9 ± 13.1. Sleep study included the following: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Berlin's Questionnaire and home-based polysomnography. Psychometric evaluation included the following: Self-Administered Anxiety Scale, Beck's Depression Inventory, Maudsley's Obsessive Compulsive Inventory, Snaith-Hamilton Pleasure Scale, Eating Attitude Test. RESULTS: All patients with insomnia had psychometric scores higher than the general population, but very few patients, in both groups, had anxiety or depression scores consistent with severe mood or anxiety disorders. Comparisons between subjective and objective scores confirmed that most sleep parameters were underestimated. Patients with SSM had lower anxiety scores as compared to patients without SSM. CONCLUSIONS: The study did not succeed in identifying any predictor of sleep misperception. We speculate that a group of patients, rather than being extremely worried by their insomnia, may have a sort of agnosia of their sleep.

Low-dose "metronomic chemotherapy" with oral cyclophosphamide and methotrexate in metastatic breast cancer: a case report of extraordinarily prolonged clinical benefit.

We report the case of a 34-year-old woman affected by breast cancer that had metastasized to the bone. She had been treated with oral cyclophosphamide and methotrexate (metronomic chemotherapy) and achieved 3.5 years of clinical remission. To our knowledge, this is the first description of such a prolonged response to therapy. This case report adds weight to known data on metronomic treatment and supports further investigation of this therapy.