Vitamin D Deficiency in COVID-19 Patients and Role of Calcifediol Supplementation.

Hypovitaminosis D has been associated with worse outcome in respiratory tract infections, with conflicting opinions regarding its role in Coronavirus-19 disease (COVID-19). Our study aimed to evaluate the possible relationship between 25-OH vitamin D (25OHD) values and the following conditions in patients hospitalized for COVID-19: prognosis, mortality, invasive (IV) and non-invasive (NIV) mechanical ventilation, and orotracheal intubation (OTI). A further objective was the analysis of a possible positive effect of supplementation with calcifediol on COVID-19 severity and prognosis. We analyzed 288 patients hospitalized at the San Giovanni di Dio Hospital in Florence and the Santa Maria alle Scotte Hospital in Siena, from November 2020 to February 2021. The 25OHD levels correlated positively with the partial pressure of oxygen and FiO2 (PaO2/FiO2) ratio (r = 0.17; p < 0.05). Furthermore, when we analyzed the patients according to the type of respiratory support, we found that 25OHD levels were markedly reduced in patients who underwent non-invasive ventilation and orotracheal intubation (OTI). The evaluation of the length of hospitalization in our population evidenced a longer duration of hospitalization in patients with severe 25OHD deficiency (<10 ng/mL). Moreover, we found a statistically significant difference in the mortality rate between patients who had 25OHD levels below 10 ng/mL and those with levels above this threshold in the total population (50.8% vs. 25.5%, p = 0.005), as well as between patients with 25OHD levels below 20 ng/mL and those with levels above that threshold (38.4% vs. 24.6%, p = 0.04). Moreover, COVID-19 patients supplemented with calcifediol presented a significantly reduced length of hospitalization (p < 0.05). Interestingly, when we analyzed the possible effects of calcifediol on mortality rate in patients with COVID-19, we found that the percentage of deaths was significantly higher in patients who did not receive any supplementation than in those who were treated with calcifediol (p < 0.05) In conclusion, we have demonstrated with our study the best prognosis of COVID-19 patients with adequate vitamin D levels and patients treated with calcifediol supplementation.

Role of Advanced Glycation End-Products and Oxidative Stress in Type-2-Diabetes-Induced Bone Fragility and Implications on Fracture Risk Stratification.

Type 2 diabetes (T2D) and osteoporosis (OP) are major causes of morbidity and mortality that have arelevant health and economic burden. Recent epidemiological evidence suggests that both of these disorders are often associated with each other and that T2D patients have an increased risk of fracture, making bone an additional target of diabetes. As occurs for other diabetic complications, the increased accumulation of advanced glycation end-products (AGEs) and oxidative stress represent the major mechanisms explaining bone fragility in T2D. Both of these conditions directly and indirectly (through the promotion of microvascular complications) impair the structural ductility of bone and negatively affect bone turnover, leading to impaired bone quality, rather than decreased bone density. This makes diabetes-induced bone fragility remarkably different from other forms of OP and represents a major challenge for fracture risk stratification, since either the measurement of BMD or the use of common diagnostic algorithms for OP have a poor predictive value. We review and discuss the role of AGEs and oxidative stress on the pathophysiology of bone fragility in T2D, providing some indications on how to improve fracture risk prediction in T2D patients.

Update on the pathogenesis and genetics of Paget's disease of bone.

Studies over the past two decades have led to major advances in the pathogenesis of Paget's disease of bone (PDB) and particularly on the role of genetic factors. Germline mutations of different genes have been identified, as a possible cause of this disorder, and most of the underlying pathways are implicated in the regulation of osteoclast differentiation and function, whereas other are involved in cell autophagy mechanisms. In particular, about 30 different germline mutations of the Sequestosome 1 gene (SQSTM1) have been described in a significant proportion of familial and sporadic PDB cases. The majority of SQSTM1 mutations affect the ubiquitin-binding domain of the protein and are associated to a more severe clinical expression of the disease. Also, germline mutations in the ZNF687 and PFN1 genes have been associated to severe, early onset, polyostotic PDB with increased susceptibly to neoplastic degeneration, particularly giant cell tumor. Mutations in the VCP (Valosin Containing Protein) gene cause the autosomal dominant syndrome "Inclusion Body Myopathy, PDB, Fronto-temporal Dementia," characterized by pagetic manifestations, associated with myopathy, amyotrophic lateral sclerosis and fronto-temporal dementia. Moreover, germline mutations in the TNFRSF11A gene, which encodes for RANK, were associated with rare syndromes showing some histopathological, radiological, and clinical overlap with PDB and in two cases of early onset PDB-like disease. Likewise, genome wide association studies performed in unrelated PDB cases identified other potential predisposition genes and/or susceptibility loci. Thus, it is likely that polygenic factors are involved in the PDB pathogenesis in many individuals and that modifying genes may contribute in refining the clinical phenotype. Moreover, the contribution of somatic mutations of SQSTM1 gene and/or epigenetic mechanisms in the pathogenesis of skeletal pagetic abnormalities and eventually neoplastic degeneration, cannot be excluded. Indeed, clinical and experimental observations indicate that genetic susceptibility might not be a sufficient condition for the clinical development of PDB without the concomitant intervention of viral infection, in primis paramixoviruses, and/or other environmental factors (e.g., pesticides, heavy metals or tobacco exposure), at least in a subset of cases. This review summarizes the most important advances that have been made in the field of cellular and molecular biology PDB over the past decades.

Bone Fragility in Gastrointestinal Disorders.

Osteoporosis is a common systemic disease of the skeleton, characterized by compromised bone mass and strength, consequently leading to an increased risk of fragility fractures. In women, the disease mainly occurs due to the menopausal fall in estrogen levels, leading to an imbalance between bone resorption and bone formation and, consequently, to bone loss and bone fragility. Moreover, osteoporosis may affect men and may occur as a sequela to different diseases or even to their treatments. Despite their wide prevalence in the general population, the skeletal implications of many gastrointestinal diseases have been poorly investigated and their potential contribution to bone fragility is often underestimated in clinical practice. However, proper functioning of the gastrointestinal system appears essential for the skeleton, allowing correct absorption of calcium, vitamins, or other nutrients relevant to bone, preserving the gastrointestinal barrier function, and maintaining an optimal endocrine-metabolic balance, so that it is very likely that most chronic diseases of the gastrointestinal tract, and even gastrointestinal dysbiosis, may have profound implications for bone health. In this manuscript, we provide an updated and critical revision of the role of major gastrointestinal disorders in the pathogenesis of osteoporosis and fragility fractures.

Management of lymphoma survivor patients in Italy: an evaluation by Fondazione Italiana Linfomi.

Several outpatient models for the follow-up of cancer survivors have been developed worldwide. A multidisciplinary approach is often necessary to guarantee the best monitoring of long-term toxicities. Guidelines also indicate a close education on healthy lifestyles. In this context, we have analyzed the Italian follow-up modalities of lymphoma survivors, with the aim to have a starting line to hypothesize and plan the best model for Italian hematology centers.

Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas. A pooled-data analysis of 12 clinical trials of Fondazione Italiana Linfomi (FIL).

Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs. Data for VTE occurrence were retrieved from study databases and pharmacovigilance reports. Our analysis includes 1717 patients from 12 prospective phase II and III trials, including newly diagnosed NHL. We observed 53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The cumulative incidences for "all-grade" or grade ≥3 VTEs were 2.9 % (95 % CI: 2.1-3.8) and 1.1 % (95 % CI: 0.6-1.6), respectively. KS categories were positively associated with the risk of VTE of any grade, and with severe events (i. e. grade ≥3; Gray's test p-values = 0.048 and 0.012, respectively). Among NHL patients, those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any grade) VTE (HR: 3.42, 95 % CI: 1.32-8.84, p-value = 0.011). Our study indicates that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of VTE events and 3) DLBCL histotype is an independent risk factor for VTE incidence, for which preventative interventions could be considered.

Bonding effectiveness of two adhesive luting cements to glass fiber posts: pull-out evaluation of three different post surface conditioning methods.

The purpose of this study was to evaluate the bond strength at the post/resin-cement interface with 3 different surface treatments of glass fiber posts and with 2 different luting resin cements. Sixty glass fiber posts (RelyX Fiber Post) were randomly divided into 3 groups (n = 20) and were luted with a dual-polymerizing self-adhesive universal resin cement (RelyX Unicem) and with a dual-polymerizing resin cement (RelyX ARC). This was carried out in association with a dual-polymerizing adhesive (Scotchbond Multi-Purpose Plus) in simulated plexiglass root canals after receiving three different pretreatment procedures. A pull-out test was performed on each sample to measure bond strengths. Data were analyzed with two-way ANOVA. Two samples from each group were processed for SEM observations in order to investigate the morphologic aspect of the post/cement interface. Both resin cements demonstrated significant different bond strength values (P < 0.0001). The surface treatment result was also statistically significant (P = 0.0465). SEM examination showed a modification of the post surface after pretreatment with methyl methacrylate. The dual-polymerizing self-adhesive universal resin cement achieved higher MPa bond strength values. The use of methyl methacrylate as a surface treatment of glass fiber posts provided a significant increase in bond strengths between the posts and both luting materials.