Bevacizumab Treatment for Patients with NF2-Related Schwannomatosis: A Single Center Experience.

(1) Background: NF2-related schwannomatosis, characterized by the development of bilateral vestibular schwannomas, often necessitates varied treatment approaches. Bevacizumab, though widely utilized, demonstrates variable effectiveness on hearing and tumor growth. At the same time, (serious) adverse events have been frequently reported. (2) Methods: A single center retrospective study was conducted, on NF2-related schwannomatosis patients treated with bevacizumab from 2013 to 2023, with the aim to assess treatment-related and clinical outcomes. Outcomes of interest comprised hearing, radiologic response, symptoms, and adverse events. (3) Results: Seventeen patients received 7.5 mg/kg bevacizumab for 7.1 months. Following treatment, 40% of the patients experienced hearing improvement, 53%, stable hearing, and 7%, hearing loss. Vestibular schwannoma regression occurred in 31%, and 69% remained stable. Further symptomatic improvement was reported by 41%, stable symptoms by 47%, and worsened symptoms by 12%. Treatment discontinuation due to adverse events was observed in 29% of cases. Hypertension (82%) and fatigue (29%) were most frequently reported, with no occurrences of grade 4/5 toxicities. (4) Conclusion: Supporting previous studies, bevacizumab demonstrated positive effects on hearing, tumor control, and symptoms in NF2-related schwannomatosis, albeit with common adverse events. Therefore, careful consideration of an appropriate management strategy is warranted.

Health-related quality of life and treatment effects in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis.

INTRODUCTION: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are often diagnosed in an advanced stage. As the optimal sequence of therapy remains largely unclear, all treatment-related outcomes, including health-related quality of life (HRQoL) prospects, should be assessed according to patients' preferences. METHODS: A targeted search was performed in PubMed and EMBASE to identify studies on treatment effect and HRQoL, measured using the EORTC QLQ-C30 tool, in patients with advanced, well-differentiated GEPNENs. Study quality was assessed, and meta-analyses were performed for global health status/QOL and tumour response. RESULTS: The search yielded 1,322 records, and 20 studies were included, examining somatostatin analogues (SSA), peptide receptor radionuclide therapies (PRRT), chemotherapy, SSA-based combination therapies, and targeted therapies. Global HRQoL was stable, and rates for disease stabilisation were moderate to high across all treatments. Meta-analyses for global health status/QOL after SSA treatment were not significant (mean difference: -0.3 [95% CI: -1.3 to 0.7]). The highest pooled overall tumour response rate was 33% (95% CI: 24-45%) for PRRT. The highest pooled clinical benefit rate was 94% (95% CI: 65-99%) for chemotherapy. CONCLUSION: All treatments appeared beneficial for disease stabilisation while maintaining stable global health status/QOL. High-quality HRQoL reporting was lacking. HRQoL should be a central outcome next to well-established outcomes.

(18)F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced hypoglycemia and mild cold exposure in non-diabetic adults.

OBJECTIVE: Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue (18)F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography. METHODS: In nine healthy adults (18)F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17 °C) during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using a hyperinsulinemic glucose clamp. RESULTS: Brown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5) g/mL (p=0.7). Similarly there were no differences in mean standardized (18)F-fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6 °C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones. CONCLUSIONS: This study shows that there is a similar amount of (18)F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase.

Fasting and postprandial activity of brown adipose tissue in healthy men.

UNLABELLED: The role of brown adipose tissue (BAT) in adult metabolism is poorly understood. This study aimed to examine the differential effects of an overnight fast and the postprandial state on BAT activity. METHODS: We included 10 healthy, lean male volunteers. BAT uptake of glucose was visualized using (18)F-FDG PET/CT during mild cold exposure. Each subject underwent PET/CT twice. The first scan was obtained after an overnight fast; the second after a standardized meal. RESULTS: (18)F-FDG uptake in BAT was observed in 6 of 10 volunteers. These subjects were found to have a higher maximal standardized uptake value when fasting (median, 13.1 g/mL; range, 6.1-27.6 g/mL) than when in the postprandial state (median, 6.8 g/mL; range, 2.1-13.4 g/mL) (P = 0.03). CONCLUSION: Cold-stimulated (18)F-FDG uptake by BAT in humans is more pronounced during fasting. The lower maximal standardized uptake value in the postprandial state may be explained by increased insulin-stimulated glucose uptake in muscle.

Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes.

AIMS: The present study sought to ascertain the prevalence of impaired awareness of hypoglycaemia (IAH) in people with insulin-treated Type 2 diabetes (T2DM) and its effect on risk of hypoglycaemia. METHODS: Data were obtained from 122 people with insulin-treated T2DM (63 male; mean (SD) HbA1c 8.4% (1.5); median (inter quartile range, IQR) age, 67 (58-72) years; duration of T2DM 15 (10-20) years; duration of insulin therapy, 6 (4-9) years). A questionnaire was used to evaluate hypoglycaemia awareness status and estimate the frequency of severe hypoglycaemia (SH) in the preceding year. Capillary blood glucose was monitored prospectively over a 4-week period to document biochemical hypoglycaemia. RESULTS: The prevalence of IAH was 9.8%. In the subgroup with IAH the incidence of SH in the preceding year was 17-fold higher than those with normal hypoglycaemia awareness (0.83 (1.12) vs. 0.05 (0.28) episodes per patient; p<0.001 (n=122)) and had a five-fold higher incidence of biochemical hypoglycaemia (2.43 (4.39) vs. 0.46 (1.21) episodes; p<0.001 (n=63)). CONCLUSION: The prevalence of IAH in insulin-treated T2DM was associated with higher frequencies of SH and biochemical hypoglycaemia. Therefore the presence of IAH in those with insulin-treated T2DM should be evaluated at clinical review.