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Background: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. Objective: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Conclusions: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)—a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)—in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9–12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (−16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (−3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs.

Parathyroid carcinoma (PC) is a very rare endocrine cancer with aggressive behavior, a high metastatic potential, and a poor prognosis. Surgical resection of affected gland(s) and other involved structures is the elective therapy. Pre-operative and intra-operative differential diagnosis with benign parathyroid adenoma remains a challenge. The lack of a clear pre-operative diagnosis does not allow one, in many cases, to choose the correct surgical approach to malignant PC, increasing persistence, the recurrence rate, and the risk of metastases. An initial wrong diagnosis of parathyroid adenoma, with a minimally invasive parathyroidectomy, is associated with over 50% occurrence of metastases after surgery. Genetic testing could help in identifying patients at risk of congenital PC (i.e., CDC73 gene) and in driving the choice of neck surgery extension. Targeted effective treatments, other than surgery, for advanced and metastatic PC are needed. The pathogenesis of malignant parathyroid carcinogenesis is still largely unknown. In the last few years, advanced molecular techniques allowed researchers to identify various genetic abnormalities and epigenetic features characterizing PC, which could be crucial for selecting molecular targets and developing novel targeted therapeutic agents. We reviewed current findings in PC genetics, epigenetics, and proteomics and state-of-the-art therapies.

Menopause, an extremely delicate phase in a woman’s life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia.

Background: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. Methods: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant’s posture in accordance with the patient’s needs). Results: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). Conclusions: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.

Vitamin D deficiency is a constantly growing health problem worldwide. Adults affected with hypovitaminosis D could experience negative consequences on their musculoskeletal system and extra-skeletal health. In fact, an optimal vitamin D status is essential to ensure the correct bone, calcium, and phosphate homeostasis. To improve vitamin D status, it is important to not only increase the intake of food fortified with vitamin D, but also to administer vitamin D supplementation when required. Vitamin D3 (cholecalciferol) is the most widely used supplement. In recent years, the administration of calcifediol (25(OH)D3), the direct precursor of the biologically active form of vitamin D3, as oral vitamin D supplementation has progressively grown. Here, we report the potential medical benefits of some peculiar biological actions of calcifediol, discussing the possible specific clinical scenarios in which the oral intake of calcifediol could be most effective to restore the correct serum levels of 25(OH)D3. In summary, the aim of this review is to provide insights into calcifediol-related rapid non-genomic responses and the possible use of this vitamin D metabolite as a supplement for the treatment of people with a higher risk of hypovitaminosis D.

Extremely preterm infants frequently require some form of respiratory assistance to facilitate the cardiopulmonary transition that occurs in the first hours of life. Current resuscitation guidelines identify as a primary determinant of overall newborn survival the establishment, immediately after birth, of adequate lung inflation and ventilation to ensure an adequate functional residual capacity. Any respiratory support provided, however, is an important contributing factor to the development of bronchopulmonary dysplasia. The risks correlated to invasive ventilatory techniques increase inversely with gestational age. Preterm infants are born at an early stage of lung development and are more susceptible to lung injury deriving from mechanical ventilation. Any approach aiming to reduce the global burden of preterm lung disease must implement lung-protective ventilation strategies that begin from the newborn’s first breaths in the delivery room. Neonatologists today must be able to manage both invasive and noninvasive forms of respiratory assistance to treat a spectrum of lung diseases ranging from acute to chronic conditions. We searched PubMed for articles on preterm infant respiratory assistance. Our narrative review provides an evidence-based overview on the respiratory management of preterm infants, especially in the acute phase of neonatal respiratory distress syndrome, starting from the delivery room and continuing in the neonatal intensive care unit, including a section regarding exogenous surfactant therapy.

Pancreatic cancer (PC) is a malignancy accounting for only 3% of total cancers, but with a low 5-year relative survival rate. Approximately 80% of PC patients are diagnosed at a late stage when the disease has already spread from the primary site. Despite advances in PC treatment, there is an urgently needed for the identification of novel therapeutic strategies for PC, particularly for patients who cannot undergo classical surgery. Autophagy is an evolutionarily conserved process used by cells to adapt to metabolic stress via the degrading or recycling of damaged or unnecessary organelles and cellular components. This process is elevated in PC and, thus, it contributes to the onset, progression, and cancer cell resistance to chemotherapy in pancreatic tumors. Autophagy inhibition has been shown to lead to cancer regression and to increase the sensitivity of pancreatic cells to radiation and chemotherapy. Emerging studies have focused on the roles of non-coding RNAs (ncRNAs), such as miRNAs, long non-coding RNAs, and circular RNAs, in PC development and progression. Furthermore, ncRNAs have been reported as crucial regulators of many biological processes, including autophagy, suggesting that ncRNA-based autophagy targeting methods could be promising novel molecular approaches for specifically reducing autophagic flux, thus improving the management of PC patients. In this review, we briefly summarize the existing studies regarding the role and the regulatory mechanisms of autophagy-related ncRNAs in the context of this cancer.

Pituitary adenomas (PAs) are one of the most common lesions of intracranial neoplasms, occurring in approximately 15% of the general population. They are typically benign, although some adenomas show aggressive behavior, exhibiting rapid growth, drug resistance, and invasion of surrounding tissues. Despite ongoing improvements in diagnostic and therapeutic strategies, late first diagnosis is common, and patients with PAs are prone to relapse. Therefore, earlier diagnosis and prevention of recurrence are of importance to improve patient care. MicroRNAs (miRNAs) are short non-coding single stranded RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies indicate that a deregulation of their expression patterns is related with pituitary tumorigenesis, suggesting that these small molecules could play a critical role in contributing to tumorigenesis and the onset of these tumors by acting either as oncosuppressors or as oncogenes, depending on the biological context. This paper provides an overview of miRNAs involved in PA tumorigenesis, which might serve as novel potential diagnostic and prognostic non-invasive biomarkers, and for the future development of miRNA-based therapeutic strategies for PAs.

Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation.

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

D-Galactose/D-glucose-binding protein from E. coli (GGBP) is a monomer thatbinds glucose with high affinity. The protein structure of GGBP is organized in twoprincipal domains linked by a hinge region that form the sugar-binding site. In this workwe show that the mutant form of GGBP at the amino acid position 182 can be utilized as aprobe for the development of a non-consuming analyte fluorescence biosensor to monitorthe glucose level in diabetes health care.