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Abstract We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Abstract Introduction Migraine is a recurrent, disabling neurological disorder with a substantial global disease burden. However, limited real-world data are available on the patient characteristics, treatment patterns, comorbidities, and economic burden of migraine in the United Arab Emirates (UAE). In this study, we evaluated the disease burden, comorbidities, treatment patterns, specialties involved in migraine diagnosis, and healthcare resource utilization (HCRU) and associated costs in patients with migraine in Dubai, UAE. Methods A retrospective, secondary database cohort study was conducted from 01 January 2014 to 31 March 2022 using the Dubai Real-World Database. Patients aged ≥ 18 years with at least one diagnosis claim for migraine with continuous enrollment during the study period were included. Patients were stratified into treatment sub-cohorts. Outcomes were evaluated in terms of clinical characteristics, comorbidities, specialists visited, treatment patterns, and HCRU. Results The study included 203,222 patients (mean age: 40 years), with male predominance (55.4%). About 13.4% of patients had specific cardiovascular comorbidities. Frequently prescribed drug classes were nonsteroidal anti-inflammatory drugs (84.4%), triptans (29.8%), and beta-blockers (12.8%), while only 1.0% of patients with migraine were prescribed newer medications like calcitonin gene-related peptide antagonists. General medicine was the most frequently visited specialty on the index date (51.5%). The all-cause and migraine-specific median gross costs during the 12-month post-index period were US $1252.6 (2.4–564,740.7) and US $198.1 (0–168,903.3) respectively, with maximum contribution from inpatients. The contribution of migraine-specific median costs to all-cause median costs was highest for the diagnosis-related group (64.9%), followed by consumables (35.2%), medications (32.0%), procedures (24.5%), and services (24.5%). Conclusion Migraine significantly impacts healthcare costs in the UAE. The role of newer therapies in migraine management should be explored to reduce the associated socioeconomic burden and improve patients’ quality of life.

Abstract Introduction Migraine is a common debilitating neurological disorder affecting a large proportion of the general population. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, plays a key role in the pathophysiology of migraine, and the development of therapies targeting the anti-CGRP pathway has revolutionized the field of migraine treatment. Methods An expert task force of neurologists in the United Arab Emirates (UAE) developed and critically assessed recommendations on the use of CGRP-based therapies in migraine treatment and management in the UAE, based on available published literature. A consensus was reached for each statement by means of an open-voting process, based on a predefined agreement level of at least 60%. Results The consensus recommendations advocate the need for guidelines for the appropriate use of CGRP-based therapies by defining patient cohorts and appropriate monitoring of therapeutic response as well as standardizing the initiation, assessment, and cessation of treatment. The consensus recommendations were primarily formulated on the basis of international studies, because of the limited availability of regional and local data. As such, they may also act as guidelines for global healthcare providers. Conclusions These are the first consensus recommendations for the UAE that address the use of CGRP-based therapies in the treatment and management of migraine, integrating both clinical evidence and medical expertise to enhance clinical judgment and decision-making.

Abstract Background The prevalence of prediabetes is increasing in the global population and its metabolic derangements may expose to a higher risk to develop type 2 diabetes (T2D) and its cardiovascular burden. Lifestyle modifications might have considerable benefits on ameliorating metabolic status. Alternative biomarkers, such as circulating miR-21, has been recently discovered associated with dysglycemia. Here we evaluated, in a longitudinal cohort of dysglycemic population the relation between the circulating miR-21/ROS/HNE levels and the habit-intervention (HI) after 1 year of follow-up. Methods 1506 subjects from DIAPASON study were screened based on the Findrisc score. Of them, 531 subjects with Findrisc ≥ 9 were selected for dysglycemia (ADA criteria) and tested for circulating miR-21, ROS and HNE levels, as damaging-axis. 207 subjects with dysglycemia were re-evaluated after 1-year of habit intervention (HI). Repeated measures tests were used to evaluate changes from baseline to 1-year of follow-up. The associations between glycemic parameters and miR-21/ROS/HNE were implemented by linear regression and logistic regression models. Results After HI, we observed a significant reduction of miR-21/ROS/HNE axis in dysglycemic subjects, concomitantly with ameliorating of metabolic parameters, including insulin resistance, BMI, microalbuminuria, reactive hyperemia index and skin fluorescence. Significant positive interaction was observed between miR-21 axis with glycaemic parameters after HI. Lower miR-21 levels after HI, strongly associated with a reduction of glycemic damaging-axis, in particular, within-subjects with values of 2hPG

Background. The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods. With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results. No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P

Abstract Background Erenumab is a calcitonin gene-related peptide (CGRP)-receptor antibody inhibiting CGRP function. CGRP is prominently involved in the pathophysiology of migraine through nociceptive modulation in the trigeminovascular system. This study aims to explore the treatment effect of erenumab in a real-life setting. Methods In this retrospective observational study, we analyzed the data of 91 patients with migraine receiving at least three consecutive monthly injections of erenumab and followed up for 3–12 months. The primary objective was to describe the reduction in monthly migraine days throughout the follow-up period. To identify patients who responded to treatment, we analyzed the association between different patient characteristics and their treatment outcomes. Results Seventy-three patients (80.2%) responded to erenumab treatment, defined as ≥50% reduction of migraine days per month, across all migraine types. It was noted that ethnicity (p-value = 0.015) and older age (p-value = 0.035) were associated with clinically relevant improvement of symptoms. Middle Eastern ethnicity was related to less improvement of symptoms while Europeans were more likely to benefit from erenumab therapy (odds ratio: 12.788, p = 0.037). Patients aged from 31 to 40 and 41–65 years benefited most from erenumab treatment with a response rate of 77.8 and 89.9%, respectively, also confirmed by logistic regression (p = 0.047). Neither gender nor dose increase of erenumab showed association with the reported clinically relevant improvement of the symptoms. An association between clinically relevant improvement of headaches and the type of migraine was also noted. Around 87.9% of patients with episodic migraine responded to treatment, followed by 84.1% of chronic migraine patients and 50% of medication overuse headache patients. Medication overuse headache showed a lower probability of therapy success with erenumab (odds ratio: 0.126, p = 0.039). An improvement of headaches was eminent in patients who received 140 mg erenumab monthly (2 × 70 mg injections) and patients who had one injection every two weeks. Conclusions Erenumab is a novel preventive treatment for all migraine types. Clinically relevant improvement of headaches and reduction of monthly migraine days were demonstrated in patients that continued the treatment course. In real-life, a substantial number of patients suspended therapy early, reasons for which need further investigation.

Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.

Introduction: Migraine is a recurrent, disabling neurological disorder with a substantial global disease burden. However, limited real-world data are available on the patient characteristics, treatment patterns, comorbidities, and economic burden of migraine in the United Arab Emirates (UAE). In this study, we evaluated the disease burden, comorbidities, treatment patterns, specialties involved in migraine diagnosis, and healthcare resource utilization (HCRU) and associated costs in patients with migraine in Dubai, UAE. Methods: A retrospective, secondary database cohort study was conducted from 01 January 2014 to 31 March 2022 using the Dubai Real-World Database. Patients aged ≥ 18 years with at least one diagnosis claim for migraine with continuous enrollment during the study period were included. Patients were stratified into treatment sub-cohorts. Outcomes were evaluated in terms of clinical characteristics, comorbidities, specialists visited, treatment patterns, and HCRU. Results: The study included 203,222 patients (mean age: 40 years), with male predominance (55.4%). About 13.4% of patients had specific cardiovascular comorbidities. Frequently prescribed drug classes were nonsteroidal anti-inflammatory drugs (84.4%), triptans (29.8%), and beta-blockers (12.8%), while only 1.0% of patients with migraine were prescribed newer medications like calcitonin gene-related peptide antagonists. General medicine was the most frequently visited specialty on the index date (51.5%). The all-cause and migraine-specific median gross costs during the 12-month post-index period were US $1252.6 (2.4–564,740.7) and US $198.1 (0–168,903.3) respectively, with maximum contribution from inpatients. The contribution of migraine-specific median costs to all-cause median costs was highest for the diagnosis-related group (64.9%), followed by consumables (35.2%), medications (32.0%), procedures (24.5%), and services (24.5%). Conclusion: Migraine significantly impacts healthcare costs in the UAE. The role of newer therapies in migraine management should be explored to reduce the associated socioeconomic burden and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Spagnolli, Massignan, Astolfi et al. design a new drug discovery approach, termed Pharmacological Protein Inactivation by Folding Intermediate Targeting, in which folding intermediates of disease-causing proteins are targeted. They test it on the cellular prion protein, identifying ligands stabilizing a folding intermediate and consequently promoting its degradation by the cellular quality control machinery.

Background: Experimental investigations and clinical observations have shown that not only faces but also voices are predominantly processed by the right hemisphere. Moreover, right brain-damaged patients show more difficulties with voice than with face recognition. Finally, healthy subjects undergoing right temporal anodal stimulation improve their voice but not their face recognition. This asymmetry between face and voice recognition in the right hemisphere could be due to the greater complexity of voice processing. Methods: To further investigate this issue, we tested voice and name recognition in twelve congenitally blind people. Results: The results showed a complete overlap between the components of voice recognition impaired in patients with right temporal damage and those improved in congenitally blind people. Congenitally blind subjects, indeed, scored significantly better than control sighted individuals in voice discrimination and produced fewer false alarms on familiarity judgement of famous voices, corresponding to tests selectively impaired in patients with right temporal lesions. Conclusions: We suggest that task difficulty is a factor that impacts on the degree of its lateralization.