Immune Checkpoint Blockade in Lung Carcinoids with Aggressive Behaviour: One More Arrow in Our Quiver?

Lung carcinoids are well-differentiated and low-/intermediate-grade neuroendocrine neoplasms of the lung. Given their relative rarity, and the paucity of data available from prospective studies, no global consensus exists on the systemic treatment of these tumours. In recent years, immune checkpoint inhibitors have revolutionized cancer management and are under evaluation in patients with diverse types of neuroendocrine neoplasms. The aim of this narrative review is to analyse all available data for the use of approved immune checkpoint inhibitors in patients with lung carcinoids. We performed an extensive search for relevant data sources and found five published articles, one meeting abstract, and nine registered clinical trials indicating a growing interest of researchers in this field, and providing preliminary evidence of efficacy for combined nivolumab plus ipilimumab and durvalumab plus tremelimumab regimens in the treatment of advanced and/or metastatic lung carcinoids

Efficacy and safety of flash glucose monitoring in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis

INTRODUCTION: Flash glucose monitoring (FGM) is a factory-calibrated sensor-based technology for the measurement of interstitial glucose. We performed a systematic review and meta-analysis to assess its efficacy and safety in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched in July 2019. Twelve studies with a follow-up longer than 8 weeks, evaluating 2173 patients on prandial insulin, multiple daily insulin injections or continuous subcutaneous insulin infusion were included. The following data were extracted: HbA1c, time in range, time above 180 mg/dL, time below 70 mg/dL, frequency of hypoglycemic events, number of self-monitoring of blood glucose (SMBG) measurements, total daily insulin dose, patient-reported outcomes, adverse events, and discontinuation rate. A comparison with SMBG was conducted. RESULTS: FGM use was associated with a reduction in HbA1c (-0.26% (-3 mmol/mol); p=0.002) from baseline to the last available follow-up, which correlated with HbA1c levels at baseline (-0.4% (-4 mmol/mol) for each 1.0% (11 mmol/mol) of HbA1c above 7.2% (55 mmol/mol)). Also, a decrease in time below 70 mg/dL was found (-0.60 hours/day; p=0.04). Favorable findings in patient-reported outcomes and no device-related serious adverse events were reported. When compared with SMBG, FGM was characterized by no statistically different change in HbA1c (p=0.09), with lower number of SMBG measurements per day (-3.76 n/day; p<0.001) and risk of discontinuation (relative risk=0.42; p=0.001). A limited number of studies, with a heterogeneous design and usually with a short-term follow-up and without specific training, were found. CONCLUSIONS: The present review provides evidence for the use of FGM as an effective strategy for the management of diabetes

Late Endocrine and Metabolic Sequelae and Long‐Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B‐Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi

Background: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment‐related sequelae has been observed as a counterpart. Method: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine‐metabolic sequelae, (ii) evaluate the effects of modern therapeutic approaches on incidence or prevalence of late endocrine‐metabolic sequelae, and (iii) determine whether there is evidence of follow‐up schemes for their screening/early diagnosis in the subset of long‐term classical Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL) survivors treated at adult age. The MEDLINE, Embase and the Cochrane Library databases were searched for relevant articles published up to October, 2020. The study selection process was conducted by three independent reviewers and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A risk of bias assessment was performed using the Cochrane tool for randomized trials and the Newcastle‐Ottawa Scale for observational studies. Results: In the final analysis, eight studies were included, four of which focused on thyroid disease, two on gonadal dysfunction, one on bone disease and one on metabolic syndrome. Hypothyroidism was reported in up to 60% of adult cHL survivors and was frequently recorded even with modern radiotherapy approaches. Menopause occurred in 52–72% of women after chemotherapy. An 86% reduction in vertebral density was reported following R‐CHOP‐like chemotherapy. Sarcopenia and metabolic syndrome were reported in 37.9% and 60% of patients, respectively. No validated screening protocols were found for the early diagnosis of long‐term treatment‐related endocrine and metabolic sequelae, thus the authors finally suggest the execution of screening exams according to the risk category which were identified in the epidemiologic studies

Structured self-monitoring of blood glucose is associated with more appropriate therapeutic interventions than unstructured self-monitoring: A novel analysis of data from the PRISMA trial

Aims: To investigate the relationship between single therapeutic interventions and indicators of glycemic control in the PRISMA trial, a large study comparing the effects of intensive structured SMBG (ISM) vs. active control (AC) in non-insulin-treated type 2 diabetes (T2D). Methods: Information was collected at four time points, corresponding to months 3, 6, 9, and 12 and visits 2, 3, 4, and 5, respectively. Data on therapeutic interventions, HbA1c levels and the number of hypoglycemic episodes at each visit were analyzed. Results: Intensification of drug therapy occurred in 20.3% vs. 15.6%, and no change in 71.8% vs. 78.7% of visits for the ISM and AC groups, respectively. On the other hand, de-intensification and redistribution of drugs and/or drug dose occurred in a similar proportion of visits. Intensification of drug therapy in both groups was associated with significant reductions in HbA1c vs. the previous visit, while de-intensification of therapy led to a significant increase in HbA1c in the AC group only. Conclusions. Our data strongly support that structured SMBG has clinical value in reducing HbA1c in non-insulin-treated T2D and suggest that this clinical benefit may be mediated by more appropriate and timely changes in drug therapy

Clinical use of a 180-day implantable glucose sensor improves glycated haemoglobin and time in range in patients with type 1 diabetes

Aims: This real-world study evaluated the changes in glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics associated with use of the implantable 180-day Eversense CGM System (Eversense) in patients with type 1 diabetes. Materials and methods: This was a prospective, multicentre, observational study among adult participants aged ≥18 years with type 1 diabetes across seven diabetes-care centres in Italy who had Eversense inserted for the first time. HbA1c was measured at baseline and at 180 days. Changes in time in range [TIR (glucose 70–180 mg/dL)], time above range [TAR (glucose >180 mg/dL)], time below range [TBR (glucose <70 mg/dL)] and glycaemic variability were also assessed. Data were also analysed by previous CGM use and by mode of insulin delivery. Results: One-hundred patients were enrolled (mean age 36 ± 12 years, mean baseline HbA1c 7.4 ± 0.92% [57 ± 10 mmol/mol]). Fifty-six per cent of patients were users of the continuous subcutaneous insulin infusion pump and 45% were previous users of CGM. HbA1c significantly decreased in patients after 180 days of sensor wear (−0.43% ± 0.69%, 5 ± 8 mmol/mol, P < 0.0001). As expected, CGM-naïve patients achieved the greatest reduction in HbA1c (−0.74% ± 0.48%, 8 ± 5 mmol/mol). TIR significantly increased and TAR and mean daily sensor glucose significantly decreased while TBR did not change after 180 days of sensor wear. Conclusions: Real-world clinical use of the Eversense CGM System for 180 days was associated with significant improvements in HbA1c and CGM metrics among adults with type 1 diabetes. The study is registered on clinicaltrials.gov (NCT04160156)

Viscoelastic gels of guar and xanthan gum mixtures provide long-term stabilization of iron micro- and nanoparticles

Iron micro- and nanoparticles used for groundwater remediation and medical applications are prone to fast aggregation and sedimentation. Diluted single biopolymer water solutions of guar gum (GG) or xanthan gum (XG) can stabilize these particles for few hours providing steric repulsion and by increasing the viscosity of the suspension. The goal of the study is to demonstrate that amending GG solutions with small amounts of XG (XG/GG weight ratio 1:19; 3 g/L of total biopolymer concentration) can significantly improve the capability of the biopolymer to stabilize highly concentrated iron micro- and nanoparticle suspensions. The synergistic effect between GG and XG generates a viscoelastic gel that can maintain 20 g/L iron particles suspended for over 24 h. This is attributed to (i) an increase in the static viscosity, (ii) a combined polymer structure the yield stress of which contrasts the downward stress exerted by the iron particles, and (iii) the adsorption of the polymers to the iron surface having an anchoring effect on the particles. The XG/GG viscoelastic gel is characterized by a marked shear thinning behavior. This property, coupled with the low biopolymer concentration, determines small viscosity values at high shear rates, facilitating the injection in porous media. Furthermore, the thermosensitivity of the soft elastic polymeric network promotes higher stability and longer storage times at low temperatures and rapid decrease of viscosity at higher temperatures. This feature can be exploited in order to improve the flowability and the delivery of the suspensions to the target as well as to effectively tune and control the release of the iron particle

Reversal of <i>MYB </i>-dependent suppression of <i>MAFB </i>expression overrides leukaemia phenotype in MLL-rearranged AML

Abstract The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias