Oncological patterns of care and outcomes for 265 elderly patients with newly diagnosed glioblastoma in France

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS _n?=?95) or biopsy (B _n?=?170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT _n?=?76), chemotherapy (CT _n?=?52), and concomitant radiochemotherapy (CRC _n?=?39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B?+?RT and/or CT, RS?±?RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT _n?=?41, 199_[155–280]; B-CRC _n?=?21, 318_[166–480]; B-RT _n?=?37, 149_[130–214]; RS-CT _n?=?11, 245_[211–na]; RS-CRC _n?=?18, 372_[349–593]; RS-RT _n?=?39, 269_[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.     

Long-term survival in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Insights from a referral center in Portugal

Objectives

This study aims to assess the long-term survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients followed in a Portuguese pulmonary hypertension (PH) referral center.

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

Purpose

Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits.

Methods

The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet.

Results

Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r ² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r ² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses.

Conclusion

Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.     

Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory.     

Acute metabolic responses after continuous or interval exercise in post-menopausal women with overweight or obesity

This pilot study compared the effects of acute high-intensity intermittent exercise (HIIE) and moderate-intensity continuous exercise (MICE) on post-exercise VO₂, fat utilization, and 24-hours energy balance to understand the mechanism of higher fat mass reduction observed after high-intensity interval training in post-menopausal women with overweight/obesity. 12 fasted women (59.5 ± 5.8 years; BMI: 28.9 ± 3.9 kg·m⁻²) completed three isoenergetic cycling exercise sessions in a counterbalanced, randomized order: (a) MICE [35 minutes at 60%-65% of peak heart rate, HR_max], (b) HIIE 1 [60 × (8-s cycling-12-s recovery) at 80%-90% of HR_max], and (c) HIIE 2 [10 × 1min at 80%-90% of HR_max − 1-min recovery]. Then, VO₂ and fat utilization measured at rest and during the 2 hours post-exercise, enjoyment, perceived exertion, and appetite recorded during the session and energy intake (EI) and energy expenditure (EE) assessed over the next 24 hours were compared for the three modalities. Overall, fat utilization increased after exercise. No modality effect or time-modality interaction was observed concerning VO₂ and fat oxidation rate during the 2 hours post-exercise. The two exercise modalities did not induce specific EI and EE adaptations, but perceived appetite scores at 1 hour post-exercise were lower after HIIE 1 and HIIE 2 than MICE. Perceived exertion was higher during HIIE 1 and HIIE 2 than MICE, but enjoyment did not differ among modalities. The acute HIIE responses did not allow explaining the greater fat mass loss observed after regular high-intensity interval training in post-menopausal women with overweight/obesity. More studies are needed to understand the mechanisms involved in such adaptations.     

Identification of prognostic markers in diffuse midline gliomas H3K27M‐mutant

Pediatric diffuse midline gliomas are devastating diseases. Among them, diffuse midline gliomas H3K27M‐mutant are associated with worse prognosis. However, recent studies have highlighted significant differences in clinical behavior and biological alterations within this specific subgroup. In this context, simple markers are needed to refine the prognosis of diffuse midline gliomas H3K27M‐mutant and guide the clinical management of patients. The aims of this study were (i) to describe the molecular, immunohistochemical and, especially, chromosomal features of a cohort of diffuse midline gliomas and (ii) to focus on H3K27M‐mutant tumors to identify new prognostic markers. Patients were retrospectively selected from 2001 to 2017. Tumor samples were analyzed by immunohistochemistry (including H3K27me3, EGFR, c‐MET and p53), next‐generation sequencing and comparative genomic hybridization array. Forty‐nine patients were included in the study. The median age at diagnosis was 9 years, and the median overall survival (OS) was 9.4 months. H3F3A or HIST1H3B mutations were identified in 80% of the samples. Within the H3K27M‐mutant tumors, PDGFRA amplification, loss of 17p and a complex chromosomal profile were significantly associated with worse survival. Three prognostic markers were identified in diffuse midline gliomas H3K27M‐mutant: PDGFRA amplification, loss of 17p and a complex chromosomal profile. These markers are easy to detect in daily practice and should be considered to refine the prognosis of this entity.