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With regard to Dr. Wimalawansa’s comment [...]

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation.

The selective and localized delivery of active agents to neoplasms is crucial to enhance the chemotherapeutic efficacy while reducing the associated side effects. The encapsulation of chemotherapeutics in nanoparticles decorated with targeting agents is a strategy of special interest to improve drug delivery. However, serum protein adsorption often compromises the

Helicobacter pylori (HP) infection is a common and persistent disorder acting as a major cofactor for the development of upper gastrointestinal diseases and several extraintestinal disorders including osteoporosis. However, no prospective study assessed the effects of HP on bone health and fracture risk. We performed a HP screening in a population-based cohort of 1149 adults followed prospectively for up to 11 years. The presence of HP infection was assessed by serologic testing for serum antibodies to HP and the cytotoxin associated gene-A (CagA). The prevalence of HP infection did not differ among individuals with normal bone mineral density (BMD), osteoporosis, and osteopenia. However, HP infection by CagA-positive strains was significantly increased in osteoporotic (30%) and osteopenic (26%) patients respect to subjects with normal BMD (21%). Moreover, anti-CagA antibody levels were significantly and negatively associated with lumbar and femoral BMD. Consistent with these associations, patients affected by CagA-positive strains had a more than fivefold increased risk to sustain a clinical vertebral fracture (HR 5.27; 95% CI, 2.23-12.63; p < .0001) and a double risk to sustain a nonvertebral incident fracture (HR 2.09; 95% CI, 1.27-2.46; p < .005). Reduced estrogen and ghrelin levels, together with an impaired bone turnover balance after the meal were also observed in carriers of CagA-positive HP infection. HP infection by strains expressing CagA may be considered a risk factor for osteoporosis and fractures. Further studies are required to clarify in more detail the underlying pathogenetic mechanisms of this association. © 2020 American Society for Bone and Mineral Research (ASBMR).

BackgroundDespite recent improvements in survival due to advances in treatment, the quality of life of patients with lymphoma may be compromised by the long-term complications of chemotherapy and steroid therapy. Among these, a potentially relevant problem is bone loss and the development of fragility fractures.AimTo provide further evidence of clinical or subclinical skeletal complications in correlation with biological variables and markers of bone disease in patients with complete response to therapy.MethodA cross-sectional observational study was conducted on subjects diagnosed with lymphoma with subsequent antineoplastic treatment, disease status after therapy defined as complete response disease for at least a year now. We performed: blood chemistry tests, imaging techniques and screening tools for the assessment of functional status and quality of life (SARC-F and mini-Osteoporosis Quality of Life).ResultsApproximately 50% of patients had osteoporosis, with a prevalence of vertebral fractures of 65.5%. In most patients, we found hypovitaminosis D and high levels of parathyroid hormone (PTH). Furthermore, a statistically significant association was observed between high PTH levels and previous lymphoma treatment. Finally, the Mini-Osteoporosis Quality of life (mini-OQLQ) questionnaire demonstrated a loss of quality of life as a consequence of the change in bone status.ConclusionsPatient treatment design for personalized chemotherapy would be desirable to reduce late effects on bone. Also, early prevention programs need to be applied before starting treatment. The most benefited subpopulations could be not only elderly but also young patients.

Some studies have shown that patients who are hospitalized with severe COVID-19 also have low levels of vitamin D. It is known that vitamin D can reduce the risk of infections and down regulate the immune/inflammatory reaction.To investigate the association between vitamin D status and lymphocyte subpopulations in hospitalized pneumonia COVID-19 patients.In 33 positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with radiologic evidence of interstitial pneumonia and in 16 healthy control subjects matched for age, sex, and seasonality lymphocyte subpopulations and vitamin D levels were evaluated.The majority of patients with COVID-19 pneumonia (70.8%) presented vitamin D deficiency. The percentages of neutrophils presented a negative correlation (r = -0.74; P0.001), whereas the percentages of lymphocytes presented a positive correlation (r = 0.43; P0.01) with 25(OH)D. Moreover, vitamin D levels were positively correlated with CD3+ (r = 0.37, P0.05), CD4+ (r = 0.41, P0.05), CD8+ (r = 0.32, P0.07), and CD19+ (r = 0.38, P0.05).This preliminary study confirms the high prevalence of vitamin D deficiency in patients with COVID-19 pneumonia and that vitamin D deficiency is associated with a reduction of lymphocyte subsets and altered T-lymphocyte activation. This finding may contribute to clarify the mechanisms by which vitamin D influences the course and outcome of COVID-19 pneumonia.

Background Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26–84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.

Background Patients with type 2 diabetes (T2DM) have an increased or normal BMD; however fragility fractures represent one of the most important complications of T2DM. Aims This study aimed to evaluate whether the use of the Radiofrequency Echographic multi spectrometry (REMS) technique may improve the identification of osteoporosis in T2DM patients. Methods In a cohort of 90 consecutive postmenopausal elderly (70.5 ± 7.6 years) women with T2DM and in 90 healthy controls we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD) and total hip (TH-BMD) using a dual-energy X-ray absorptiometry device; moreover, REMS scans were also carried out at the same axial sites. Results DXA measurements were all higher in T2DM than in non-T2DM women; instead, all REMS measurements were lower in T2DM than in non T2DM women. Moreover, the percentage of T2DM women classified as “osteoporotic”, on the basis of BMD by REMS was markedly higher with respect to those classified by DXA (47.0% vs 28.0%, respectively). On the contrary, the percentage of T2DM women classified as osteopenic or normal by DXA was higher with respect to that by REMS (48.8% and 23.2% vs 38.6% and 14.5%, respectively). T2DM women with fragility fractures presented lower values of both BMD-LS by DXA and BMD-LS by REMS with respect to those without fractures; however, the difference was significant only for BMD-LS by REMS (p Conclusions Our data suggest that REMS technology may represent a useful approach to enhance the diagnosis of osteoporosis in patients with T2DM.

Purpose/objectives To investigate dental students’ perceptions and concerns regarding the COVID‐19 pandemic, their coping strategies and support resources, and their perceived stress levels. Methods A customized 19‐item survey and the perceived stress scale (PSS) were applied to undergraduate dental students from the US, Spain, Ireland, Chile, India, and Brazil between April 10 and July 5, 2020. Linear modeling and mediation analysis were used to explore the relationships among demographics, stressors, coping mechanisms, social support, and stress Results A total of 4475 students responded to the survey. The majority (72.4%) were women, and 52.3% had no COVID‐19 training at the time of the survey. The students reported that they had to accommodate to changes in patient care (96.6%) and didactic learning (95.2%) activities, while 88.5% of the respondents indicated at least one of their courses moved online. Transition to online courses went “smoothly with some troubles” for 51.8% of the respondents, and 48.3% perceived the faculty as prepared for the online transition; however, 45.9% reported feeling extremely concerned about the impact of COVID‐19 on their education. The average PSS score was 21.9 of 40 (moderate stress). Multivariate models were built for participants with full data (n = 3899). Being male, having completed more dental coursework, and perceiving a smoother transition were associated with lower PSS scores; more concern about academic progress was associated with higher PSS. Faculty support mediated the relationship between a smoothness of transition and concern about academic progress and PSS scores Conclusion Stress caused by the pandemic may be alleviated by smoother transition and good faculty support.

ODYSSEY APPRISE trial evaluated efficacy and safety of alirocumab in 994 patients with hypercholesterolemia and high CV risk in a real-life setting. The aim of the present report is to detail on the Italian cohort enrolled and treated in the trial.The methodology of the of the multinational, single-arm, Phase 3b open-label ODYSSEY APPRISE (Clinicaltrials.gov: NCT02476006) has been previously reported. 255 Italian patients were enrolled and treated according to the trial protocol. Overall mean exposure to alirocumab was 83.3 ± 27.7 weeks. At week 12, LDL-C decreased by 51.3 ± 23.1% and this reduction was overall maintained for the duration of the study. A similar reduction was observed in patients with and without heterozygous familial hypercholesterolemia (HeFH 50.7% ± 23.9 vs. non-FH, 53.6% ± 19.6). LDL-C was reduced below 1.8 mmol/L and/or by ≥ 50% reduction from baseline in 62% of patients overall (61% in HeFH and 67% in non-FH). Alirocumab was similarly well tolerated in the Italian cohort as in the entire study population and the more common treatment emergent adverse events (TEAEs) were influenza, myalgia and nasopharyngitis. The incidence LDL-C levels25 mg/dl and15 mg/dl, was 8.2% and 2.9% respectively.The efficacy and safety of alirocumab in a real-life setting, in the Italian subgroup of patients are consistent with findings in the entire study population and confirm that alirocumab is a beneficial approach to further reduce LDL-C levels in patients at high CV risk on maximally tolerated conventional lipid lowering treatment.NCT02476006.

Background At present, although cholecalciferol represents the form of vitamin D of choice for the treatment of vitamin D deficiency, there is a growing interest in calcifediol. Aims This study aimed to evaluate the efficacy and the safety of two different daily doses of calcifediol. Methods Fifty osteopenic/osteoporotic women with serum levels of 25-hydroxyvitamin D (25OHD) between 10 and 20 ng/ml were randomized to a 6-month treatment with oral calcifediol 20 µg/day (n = 25) or oral calcifediol 30 µg/day (n = 25). In all, we measured the time course of the levels of 25OHD and other biochemical parameters. Moreover, we evaluated handgrip strength and serum levels of myostatin. Results The peak increase in 25OHD levels was reached after 90 days of treatment in group 1 (59.3 ng/ml) and after only 60 days in group 2 (72.3 ng/ml); thereafter in both groups, the levels of 25OHD showed a tendency towards stabilization. After 30 days, all the patients treated with 30 µg/day had values of 25OHD > 30 ng/ml. Handgrip strength showed a modest but progressive increase which reached the statistical significance in the 30 µg/day group. This latter group also presented a modest and non-significant decrease in serum levels of myostatin. Conclusions Calcifediol is able to rapidly normalize the vitamin D deficiency, and the 30 µg daily dosage could be suggested in those patients who need to rapidly reach optimal 25OHD levels. Moreover, the 6-month treatment with calcifediol at a dose of 30 µg results in a modest but significant increase in upper limb strength.

Giovanni Iolascon,1 Alessandro de Sire,1– 3 Dario Calafiore,1,4 Maria Grazia Benedetti,5 Carlo Cisari,2,6 Giulia Letizia Mauro,7 Silvia Migliaccio,8 Ranuccio Nuti,9 Giuseppina Resmini,10 Stefano Gonnelli,9 Antimo Moretti1 1Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont “A. Avogadro”, Novara, Italy; 3Rehabilitation Unit, “Mons L. Novarese” Hospital, Vercelli, Moncrivello, Italy; 4Section of Neuromotor Rehabilitation, Department of Neuroscience, ASST Carlo Poma, Mantova, Italy; 5Physical Medicine and Rehabilitation Unit, IRCCS-Istituto Ortopedico Rizzoli, Bologna, Italy; 6Physical Medicine and Rehabilitation Unit, University Hospital “Maggiore della Carità”, Novara, Italy; 7Department of Surgical and Oncology Sciences, University of Palermo, Palermo, Italy; 8Department of Movement, Human and Health Sciences, Section of Health Sciences, University of Rome, Foro Italico, Rome, Italy; 9Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy; 10Section of Orthopaedics and Traumatology, Treviglio-Caravaggio Hospital, Treviglio, Bergamo, ItalyCorrespondence: Alessandro de SirePhysical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont “A. Avogadro”, Viale Piazza D’Armi 1, Novara 28100, ItalyTel +3903213734800Email alessandro.desire@gmail.comObjective: To assess physical performance, number of falls, previous fragility fractures, and ongoing pharmacological therapy in a cohort of post-menopausal women, according to their risk of falling.Methods: In this multicenter cross-sectional study, we recruited in a 3-year period (May 2016 to April 2019), women aged > 60 years referred to seven Osteoporosis and Bone Metabolism Outpatient Services of the Italian Group for the Study of Metabolic Bone Diseases. The study population was divided into three groups according to the risk of falling, assessed through the Elderly Fall Screening Test (EFST): low risk (EFST score=0– 1); moderate risk (EFST=2– 3); high risk (EFST=4– 5). Outcome measures were: 4-meter gait speed (4MGS); unipedal stance time (UST); number of falls in the previous year; previous fragility fractures; ongoing pharmacological therapy.Results: We analyzed 753 women (mean aged 70.1± 9.2 years): 378 (50.2%) at low risk of falling, 247 (32.8%) at moderate risk, and 128 (17.0%) at high risk. 4MGS and UST resulted as pathological in the 93.9% and 99.2%, respectively, of women at high risk. There were significant differences among groups for both outcomes (p< 0.001). There was also a significant difference among groups (p< 0.001) in terms of previous falls and fragility fractures. Lastly, there were significant differences (p< 0.05) among groups in using antihypertensive drugs, antiplatelet agents, anticoagulants, antidepressants, anti-osteoporotic drugs, and vitamin D, and/or calcium supplementation.Conclusion: Physical performance, prevalence of falls and fragility fractures, and an assessment of pharmacological therapy should be investigated in post-menopausal women because of their significant correlation with risk of falling.Keywords: accidental falls, osteoporosis, walking speed, fractures, bone, rehabilitation

Background/Aim: In 2020, because of coronavirus pandemic, medical activities changed. The aim of this report is to compare the volumes of Pisa radiotherapy activities from March 9(th )to May 31(st), 2020, with the same period in 2019. Patients and Methods: We analyzed the activity of our Unit to evaluate how logistics changes, related to the COVID-19 epidemic, impacted on volumes of radiotherapy (RT) activity and on the number of cases of COVID-19 infections observed in healthcare professionals and patients. Results: The total number of first-time visits between March-May 2020 was reduced by 18%, probably due to delays in diagnosis and histological tests as well as the temporary closure of the operating rooms. None of the healthcare professionals and only two patients contracted the infection. Conclusion: We were able to treat all patients referred to our hospital and we were able to reduce risk of infection for both our patients and healthcare staff, guaranteeing continuum of care for our oncological patients.

Purpose Tumor induced osteomalacia (TIO) is a rare disease of mineral metabolism, whose clinical picture is dominated by hypophosphatemia usually due to an excess of circulating FGF23 produced by small mesenchymal tumors. Data on the real prevalence of the disease are lacking, with the knowledge of the disease mainly relying on case reports and small case series. No estimate is available on the prevalence of uncured TIO. Methods National multi-center, cross-sectional and retrospective study on persistent or recurrent cases of TIO followed in referral centers for bone diseases; systematic review of the published persistent and recurrent cases of TIO. Data from patients consecutively evaluated in referral Italian centers for bone diseases were collected; a PubMed search on persistent, recurrent and unoperable cases of TIO was carried out. Results Sixteen patients (mean age at diagnosis 52.5 ± 10.6 years) with persistent (n = 6, 37,5%), recurrent (n = 7, 43.7%) or not operable (n = 3, 18.8%) TIO were described. Delay in diagnosis (2.5 ± 1.3 years) was demonstrated. All patients experienced fragility fractures or pseudofractures and disabling bone and muscle pain. BMD was significantly reduced (mean T-score −2.7 ± 1.7 and −2.7 ± 0.9 at lumbar spine and femoral neck, respectively). Fourteen patients were maintained under therapy with phosphate salts and calcitriol, while in 2 patients therapy with burosumab, an anti-FGF23 antibody, was commenced. Conclusion A significant number of patients with TIO remain either undiagnosed for tumor localization or tumor recur or persist after surgery. These patients with active disease represent possible candidates for burosumab treatment.

Objective This study aimed to evaluate the relationship between physical activity habits, physical performance and cognitive capacity in older adults' population of Italy and Slovenia. Methods Anthropometric characteristics and body composition bioelectrical impedance analysis (BIA) were evaluated in 892 older adults (60-80 y). Aerobic capacity was measured using the 2km walking test and handgrip and flexibility tests were performed. Physical activity habits and cognitive functions were evaluated by the Global-Physical-Activity-Questionnaires (GPAQ) and by Montreal-Cognitive-Assessment (MoCA) questionnaires, respectively. Results GPAQ scores were associated with lower BMI (r=-0.096; p=0.005), lower percentage of fat-mass (r=-0.138; p=0.001), better results in the 2km-walk test (r=-0.175; p=0.001) and a higher percentage of fat-free mass (r=0.138; p=0.001). We also evaluated that, a higher MoCA score correlates with age (r=-0.208; p=0.001), 2km-walk test (r=-0.166; p=0.001), waist-hip ratio (r=-0.200; p=0.001), resting heart-rate (r=-0.087; p=0.025) and heart-rate at the end of 2km-walk test (r=0.189; p=0.001). Conclusions Older adults with a higher level of daily physical activity showed reduction in fat mass and BMI, and higher aerobic fitness; these characteristics have a protection effect on cognitive function.

Background Osteoarthritis (OA) and vertebral fractures at the lumbar spine lead to an overestimation of bone mineral density (BMD). Recently, a new approach for osteoporosis diagnosis, defined as radiofrequency echographic multi-spectrometry (REMS), represents an innovative diagnostic tool that seems to be able to investigate bone quality and provide an estimation of fracture risk independent of BMD. The aim of this paper was to evaluate whether the use of REMS technology can favor the diagnosis of osteoporosis in subjects with an apparent increase in BMD. Methods In a cohort of 159 postmenopausal (66.2 ± 11.6 yrs) women with overestimated BMD by DXA at the lumbar spine, we performed an echographic scan with the REMS technique. Results The mean values of BMD at different skeletal sites obtained by the DXA and REMS techniques showed that the BMD T-scores by REMS were significantly lower than those obtained by the DXA technique both at the lumbar spine (p p Conclusions REMS technology by the analysis of native raw unfiltered ultrasound signals appears to be able to overcome the most common artifacts, such as OA and vertebral fracture of the lumbar spine, which affect the value of BMD by DXA.

The most recent scientific evidence supports the consumption of cow's milk and dairy products as part of a balanced diet. However, these days, the public and practicing physicans are exposed to a stream of inconsistent (and often misleading) information regarding the relationship between cow's milk intake and health in the lay press and in the media. The purpose of this article, in this context, is to facilitate doctor-patient communication on this topic, providing physicians with a series of structured answers to frequently asked patient questions. The answers range from milk and milk-derived products' nutritional function across the life span, to their relationship with diseases such as osteoporosis and cancer, to lactose intolerance and milk allergy, and have been prepared by a panel of experts from the Italian medical and nutritional scientific community. When consumed according to appropriate national guidelines, milk and its derivatives contribute essential micro- and macronutrients to the diet, especially in infancy and childhood where bone mass growth is in a critical phase. Furthermore, preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes, and cardiovascular disease, while no clear data suggest a significant association between milk intake and cancer. Overall, current scientific literature suggests that an appropriate consumption of milk and its derivatives, according to available nutritional guidelines, may be beneficial across all age groups, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy. Key teaching points: Milk and its derivatives contribute essential micro and macronutrients to the diet, when consumed according to appropriate national guidelines, especially in infancy and childhood where bone mass growth is in a critical phase. Preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes and cardiovascular disease No clear data are available about the association between milk intake and cancer. Current scientific literature suggests that an appropriate consumption of milk and its derivatives may be beneficial at all ages, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy.

There is an unmet need for new biomarkers able to predict both the outcomes of up-front therapy and the compliance of elderly patients diagnosed with glioblastoma. For this purpose, temporal muscle thickness is a promising tool to be investigated.Data from 52 glioblastoma patients older than 65 years, treated with post-operative radio or radio-chemotherapy and referred to Pisa University Hospital, were retrieved. The thickness of temporal muscle (TMT) was divided into quartiles and correlated with overall survival (Our primary endpoint). Survival curves were calculated using Kaplan-Meier method, and log-rank test was used to evaluate the differences between curves.Patients in the lower quartile of TMT, with TMT thinner than 7 mm, have survived longer; both univariate and multivariate analyses showed a statistically significant correlation between TMT and overall survival (P = 0.012 and P = 0.003, respectively).Future prospective and more extensive studies focused on elderly glioblastoma patients are needed to confirm the role of TMT as prognostic value on OS and to help explaining this association.

The present study aims to investigate the role of the first magnetic resonances (MRI) following radio-chemotherapy (RT-CT) in patients diagnosed with high-grade glioma.We retrospectively recorded radiological evaluations following RT-CT, symptoms related to disease progression (avoiding any sign due to radiotherapy or chemotherapy) and the change of therapeutic strategy.In March 2021, at data analysis, the data of 149 patients diagnosed with high-grade glioma and treated between May 2013 and July 2020 were retrieved for the present analysis. Two out of 122 (1.6%), 5 out of 106 (4.7%) and 8 out of 92 (8.6%) asymptomatic patients received the diagnosis of disease recurrence at the time of the first, second and third MRI, respectively. Otherwise, 16 out of 27 (59.2%), 16 out of 24 (66.6%) and 13 out of 16 (82.2%) symptomatic patients changed their therapy after the first, second and third MRI, respectively. Among patients that experienced radiological signs of distant progression, 10 out of 14 were symptomatic and changed their therapy.MRIs performed by 6 months after the end of RT-CT lead to change treatment strategy mostly in symptomatic patients.

It is widely reported in the literature that CD4, CD8 and total T cell count are significantly reduced in critically ill patients with COVID‐19. Few weeks ago, we suggested natural killer (NK) cell count as a marker of severity in 34 hospitalized COVID‐19 patients. On this topic, our research group firstly described a novel potential COVID19 severity marker, Krebs von den Lungen‐6. This study aimed to investigate how a combination of COVID19 severity markers could be helpful in the clinical management of these patients. The combination of these validated, reproducible and non‐expensive bioindicators showed a good accuracy in discriminating between severe and non‐severe patients, suggesting a promising value of this approach in the early prediction of a more aggressive disease phenotype. Despite its monocentric design, our study confirms the reliable dysregulation of innate immune responses, particularly involving NK cells, and suggests that surveillance of a peripheral biomarkers’ panel, including lymphocyte cell counts and KL‐6, may be useful in the clinical management of severe COVID‐19 patients. This article is protected by copyright. All rights reserved.

Radiation therapy is one of the cornerstones in the treatment of head and neck squamous cell carcinomas (HNSCC), alone or in combination with chemotherapy or surgery. Technological advances which occurred over the last few decades have increased the efficacy of radiotherapy (RT), particularly, intensity-modulated RT (IMRT). IMRT can deliver treatments on complex tumoral targets with dose escalation while sparing organs at risk; anyway IMRT deposits dose in unpredictable patterns outside of the target volume with the purpose of improving conformality. Radiation-induced nausea and vomiting (RINV) is a frequent albeit neglected side effect of RT that can lead to delays in treatment with serious consequences on cure rates. According to several guidelines (MASCC 2016, NCCN 2018), RT for HNSCC has traditionally been regarded as a low emetic risk treatment. Nevertheless, several works suggest that IMRT could increase RINV. Further studies are needed to define the exact incidence and the detailed pathophysiology of RINV in patients with HNSCC treated with state of art IMRT techniques, with and without concurrent chemotherapy.

The appropriate selection of individual-specific spinal cord epidural stimulation (scES) parameters is crucial to re-enable independent standing with self-assistance for balance in individuals with chronic, motor complete spinal cord injury, which is a key achievement toward the recovery of functional mobility. To date, there are no available algorithms that contribute to the selection of scES parameters for facilitating standing in this population. Here, we introduce a novel framework for EMG data processing that implements spectral analysis by continuous wavelet transform and machine learning methods for characterizing epidural stimulation-promoted EMG activity resulting in independent standing. Analysis of standing data collected from eleven motor complete research participants revealed that independent standing was promoted by EMG activity characterized by lower median frequency, lower variability of median frequency, lower variability of activation pattern, lower variability of instantaneous maximum power, and higher total power. Additionally, the high classification accuracy of assisted and independent standing allowed the development of a prediction algorithm that can provide feedback on the effectiveness of muscle-specific activation for standing promoted by the tested scES parameters. This framework can support researchers and clinicians during the process of selection of epidural stimulation parameters for standing motor rehabilitation.

The involvement of transactivation response (TAR) DNA-binding protein 43 (TDP-43) in neurodegenerative diseases was revealed in 2006, when it was first reported to be the main component of the intracellular inclusions in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. After 12 yr it is not yet possible to purify to a reasonable yield and in a reproducible manner a stable full-length protein, which has limited so far the characterization of its structure, function, molecular interactors, and pathobiology. Using a novel protocol we have achieved the purification of the full-length TDP-43, with both a short pectate lyase B tag and a glutathione S-transferase tag, which consisted in its expression in bacteria, solubilization from inclusion bodies, purification under denaturing conditions, refolding, and a final size exclusion chromatography (SEC) step. Differential scanning fluorimetry was used to find the best buffers and combination of additives to increase both its solubility and its stability. The protein is pure, as determined with electrophoresis, Western blotting, and mass spectrometry; properly refolded, as revealed by circular dichroism and fluorescence spectroscopies; functional, because it binds to DNA and protein partners; and stable to degradation and aggregation in a physiologic solution. Analyses with dynamic light scattering and SEC revealed that the protein is a dimer.-Vivoli Vega, M., Nigro, A., Luti, S., Capitini, C., Fani, G., Gonnelli, L., Boscaro, F., Chiti, F. Isolation and characterization of soluble human full-length TDP-43 associated with neurodegeneration.

Background: Hip fragility fractures are becoming one of the main health care problems in countries with an aging population. This study aimed to evaluate the clinical characteristics and the usefulness of bone turnover markers in patients with a hip fracture. Methods: In a cohort of 363 patients (84.1 ± 9.2 years) with hip fractures we measured 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase, type I collagen β carboxy telopeptide (βCTX), and parathyroid hormone (PTH). We recorded patients’ Charlson Comorbidity Index (CCI) and previous history of fragility fractures. Results: Vitamin D and PTH levels were inversely correlated (r = −024; p < 0.001). The prevalence of 25OHD deficiency was 57.8%, the PTH levels greater than 65 pg/mL was in 47.0 %, and in those who had βCTX values the upper limit was 61.8%. Moreover, 62% of patients with a fragility hip fracture had a history of a previous fracture. The 25OHD serum levels were inversely associated with CCI and a previous fragility fracture. On the contrary, PTH and βCTX serum levels showed a positive significant correlation with CCI and previous fragility fractures. Conclusion: This study confirmed the usefulness of a bone turnover markers assessment, along with the comorbidities and history of previous fragility fractures in order to better identify the risk of hip fracture.

The primary aim was to evaluate the association of patient-related factors, biomaterials, and implant characteristics on complications' rate of sinus graft surgery and on implant survival rate in grafted sinus. Secondary aims were to measure bone remodeling around implants and patient satisfaction. A retrospective cohort study was designed. Patients who had computerized tomography (CT) before sinus surgery (T0), orthopantomography after implant surgery (T1) and at follow-up (T2), were included. Specific forms were used to collect clinical data. Radiographic measures were: height of residual bone before sinus surgery measured on CT (T0) and apical and marginal bone levels around implants measured on orthopantomography at T1 and T2. Forty-three lateral sinus lifts were performed. Three grafts failed before implant insertion. Out of 83 implants inserted in 29 patients, a total of 19 failed. Mean follow-up (T2) was 6 ± 1.8 years [4; 11.2 years]. The multilevel models analysis showed no association between complications rate and patient-related factors, biomaterials, and implant characteristics. Smoking (odds ratio [OR]: 8.3; 95% CI 1.46–48.05, P = .0173) and height of residual bone (OR: 0.32 for each mm; 95% CI 0.15–0.68, P = .0034) were associated with implant failure. Bone remodeling between T1 and T2 was −0.8 ± 0.2 mm for apical bone and −0.6 ± 0.3 mm for marginal bone. General therapy satisfaction measured in a visual analogue scale was 8.4 ±1.4. In conclusion, lower height of residual bone before sinus surgery and smoking habits had a negative prognostic effect on survival rate of dental implants placed in grafted sinuses.

A marine sediment phytoremediated and homogenized by landfarming was tested for its potential recycle as growing media in horticulture. Two strawberry cultivars, Camarosa and Monterey, were grown on remediated sediment alone (TS100), commercial peat/pumice based growing medium (TS0) and a mixture 1:1 in volume of sediment and peat (TS50). Chemical fertility and strawberry production and safety of produced food were monitored for three consecutive productive seasons on the same growing media. During the first year of cultivation, plants grown on sediment-based media showed a significantly lower biomass production and fruit yield compared with peat, mainly due to the sediment low fertility. In the subsequent two years, the plant re-cultivation improved the sediment structure and N mineralization, and on the third cultivation year both strawberry cultivars showed higher fruit productivity and no accumulation of potentially toxic trace metals. The produced fruits did non accumulate high concentrations of trace metals, and risk assessment showed no risks for human health related to the consumption of strawberry produced on sediment-based growing media. We concluded that a phytoremediated sediment could be recycled as an ingredient of soilless growing media for reducing the environmental impact of plant nursery production and posing no risks for human health. These results show that reclaimed sediments could be reconsidered as a component material category in the new EU regulation on fertilizers. (c) 2021 Elsevier B.V. All rights reserved.

Objective The maternal bone structure is the largest calcium reserve for the fetus during pregnancy, and this is claimed to lead to a bone mineral density (BMD) reduction in pregnant women. The primary outcome of the present work was to assess the BMD in a group of healthy pregnant women. Study design In this prospective case – control observational study, a non-consecutive group of pregnant women with uncomplicated pregnancy at or >37 weeks were enrolled at the unit of Obstetrics and Gynecology, University of Parma, from February to December 2020. The study subjects were submitted to a sonographic examination of the proximal femur with Radiofrequency Echographic Multi Spectrometry (REMS) technology to quantify the BMD of the femur. The BMD values obtained in the study group were compared with those of a control group of non-pregnant women matched for age, ethnicity and pre-pregnant body mass index (BMI). Results Overall, 78 pregnant women at 39.1 ± 1.5 weeks were assessed. Compared with non-pregnant women, the femoral BMD values measured in pregnancy using REMS were significant lower (0.769 ± 0.094 g/cm2 vs 0.831 ± 0.101 g/cm2, p = 0.0001) with a mean BMD reduction of 8.1%. The femoral neck BMD presented a positive correlation with the pre-pregnant BMI (p = 0.0004) and a negative correlation with the maternal age (p Conclusion In this exploratory and proof of concept study, for the first time, a decreased BMD has been objectively demonstrated in pregnant compared with non-pregnant women by means of REMS technology. New studies are required to assess the longitudinal changes of maternal bone density throughout the pregnancy.

Background. The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to examine the impact of different patterns of GBM failure on patients’ survival and second surgery outcomes.Methods. Overall survival was assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves.Results. Contact with ventricles, a second surgery and meningeal spread had a statistically impact on patient survival after the diagnosis of GBM recurrence (P=0.032, P=0.019 and PConclusions. The local recurrence pattern could be a promising field of interest for patients with recurrent GBM suitable for a second surgery.

Aim Bone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D. Data synthesis The following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively. Conclusions Clinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.

Dual-energy X-ray absorptiometry (DXA) is considered the gold standard in the evaluation of bone mineral density (BMD) and in the diagnosis of osteoporosis.The diagnostic sensitivity of BMD at lumbar spine is frequently reduced by the presence of artifacts. This study aimed to show the usefulness of radiofrequency echographic multi-spectrometry (REMS) in determining lumbar BMD in the presence of artifacts with DXA measurements. We present 3 cases in which REMS technology, by the analysis of native raw unfiltered ultrasound signals, appears to be able to recognize and overcome the most common artifacts that affect the value of the BMD by DXA, thus allowing a better assessment of fracture risk.

Neuromuscular Electrical Stimulation (NMES) is commonly used in neuromuscular rehabilitation protocols, and its parameters selection substantially affects the characteristics of muscle activation. Here, we investigated the effects of short pulse width (200 µs) and higher intensity (short-high) NMES or long pulse width (1000 µs) and lower intensity (long-low) NMES on muscle mechanical output and fractional oxygen extraction. Muscle contractions were elicited with 100 Hz stimulation frequency, and the initial torque output was matched by adjusting stimulation intensity. Fourteen able-bodied and six spinal cord-injured (SCI) individuals participated in the study. The NMES protocol (75 isometric contractions, 1-s on–3-s off) targeting the knee extensors was performed with long-low or short-high NMES applied over the midline between anterior superior iliac spine and patella protrusion in two different days. Muscle work was estimated by torque–time integral, contractile properties by rate of torque development and half-relaxation time, and vastus lateralis fractional oxygen extraction was assessed by Near-Infrared Spectroscopy (NIRS). Torque–time integral elicited by the two NMES paradigms was similar throughout the stimulation protocol, with differences ranging between 1.4% (p = 0.877; able-bodied, mid-part of the protocol) and 9.9% (p = 0.147; SCI, mid-part of the protocol). Contractile properties were also comparable in the two NMES paradigms. However, long-low NMES resulted in higher fractional oxygen extraction in able-bodied (+ 36%; p = 0.006). Long-low and short-high NMES recruited quadriceps femoris motor units that demonstrated similar contractile and fatigability properties. However, long-low NMES conceivably resulted in the preferential recruitment of vastus lateralis muscle fibers as detected by NIRS.

Aim Pancreatic adenocarcinoma is a life-threatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies. Materials and methods Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in between-study variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird. Results Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting. Conclusion We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease.

The patients’ persistence with osteoporosis treatments is low. This retrospective, multicenter survey showed that almost 30% of osteoporotic patients discontinued the treatment within the first 6 months and that those taking drinkable bisphosphonates were less likely to interrupt the therapy; instead, the use of generic bisphosphonates was associated to a more precocious interruption. Purpose: Low persistence with osteoporosis medications is associated with higher fracture risk. This study aimed to assess the persistence to treatment with oral bisphosphonates among Italian osteoporotic patients under treatment for at least 6 months and to evaluate whether the different oral formulations of bisphosphonates may influence the interruption of the therapy. Methods: 723 consecutive osteoporotic patients, aged 50 years or over, referred as outpatients for a follow-up visit after receiving a prescription of an oral bisphosphonate for the first time for at least 6 months were enrolled in this retrospective, multicenter survey carried out under conditions of usual clinical practice. All the patients enrolled were submitted to a standardized interview. Results: 191 patients turned out to have discontinued treatment (28.7%), the more common causes for interruption being the adverse events (43.9%), fear of adverse events (23.3%) and perceived absence of efficacy of the treatment (15.8%). The osteoporotic patients taking drinkable bisphosphonate or on treatment with aromatase inhibitors or under the age of 70 years were less likely to interrupt the treatment. However, these associations were no longer significant when the pharmaceutical formulation (generic vs branded) was included into the multivariate logistic regression model. Conclusion: This study suggests that the new drinkable formulations of bisphosphonates could be an interesting option able to reduce upper GI adverse events, thus increasing persistence; whereas the generic formulations of bisphosphonates were associated to a premature discontinuation.

This study reports the results of a monocentric prospective analysis conducted with the aim of evaluating the impact of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms (SNP) on patients with high-grade glioma treated with concomitant radio-chemotherapy. From October 2010 to August 2019, a total of 75 patients aged ≥18 years, with histological diagnosis of high-grade glioma, isocitrate dehydrogenase (IDH) 1/2 wild type and treated with radio-chemotherapy and sequential chemotherapy with temozolomide (TMZ) were prospectively recruited. The local ethic committee approved this study (Comitato Etico di Area Vasta Nord Ovest [CEAVNO]; protocol 3304/2011). After a median follow up of 25 months (range: 7–98 months), median progression-free survival (PFS) and overall survival (OS) were 11 months (CI95%: 8–14 months) and 18 months (CI95%: 15–21 months), respectively. In univariate and multivariate Cox regression analysis, a statistically significant association with PFS and OS was found with XRCC3 rs1799794 SNP. The study suggests that XRCC3 rs1799794 SNP can be associated with different PFS and OS in glioblastoma patients treated with radio-chemotherapy.

Coronavirus disease 2019 (COVID-19) is a pandemic infection due to the spread of a novel coronavirus (severe acute respiratory syndrome coronavirus 2), resulting in a wide range of clinical features, from asymptomatic carriers to ARDS. The gold standard for diagnosis is nucleic acid detection by real-time reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs. However, due to limitations in this technique's sensitivity, thoracic imaging plays a crucial, complementary role in diagnostic evaluation and also allows for detection of atypical findings and potential alternative targets for sampling (eg, pleural effusion). Although less common, pleural involvement has been described in a minority of patients. This report describes the first case of reverse transcriptase-polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 in pleural fluid obtained by means of ultrasound-guided thoracentesis, and its main characteristics are detailed. Pleural effusion is not a common finding in COVID-19 infection, but a prompt recognition of this potential localization may be useful to optimize diagnostic evaluation as well as the management of these patients.

Most of our understanding of chemistry derives from atomic-level structures obtained with single-crystal X-ray diffraction. Metal centers in X-ray structures of small organometallic or coordination complexes are often extremely well-defined, with errors in the positions on the order of 10(-4)-10(-5) A. Determining the metal coordination geometry to high accuracy is essential for understanding metal center reactivity, as even small structural changes can dramatically alter the metal activity. In contrast, the resolution of X-ray structures in proteins is limited typically to the order of 10(-1) angstrom. This resolution is often not sufficient to develop precise structure-activity relations for the metal sites in proteins, because the uncertainty in positions can cover all of the known ranges of bond lengths and bond angles for a given type of metal complex. Here we introduce a new approach that enables the determination of a high-definition structure of the active site of a metalloprotein from a powder sample, by combining magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, tailored radio frequency (RF) irradiation schemes, and computational approaches. This allows us to overcome the "blind sphere" in paramagnetic proteins, and to observe and assign H-1, C-13, and N-15 resonances for the ligands directly coordinating the metal center. We illustrate the method by determining the bond lengths in the structure of the Co-II coordination sphere at the core of human superoxide dismutase 1 (SOD) with 0.7 pm precision. The coordination geometry of the resulting structure explains the nonreactive nature of the Co-II/Zn-II centers in these proteins, which allows them to play a purely structural role.

Background More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects. Methods In 232 women with Rett syndrome (mean age 13.8 ± 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe. Results As aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p p p Conclusion This study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.

To investigate the effectiveness of the T-score values provided by Radiofrequency Echographic Multi Spectrometry (REMS) in the identification of patients at risk for incident osteoporotic fractures.A population of Caucasian women (30-90 years), enrolled from 2013 to 2016, underwent dual X-ray absorptiometry (DXA) and REMS scans at axial sites. The incidence of fragility fractures was assessed during a follow-up period up to 5 years. Afterwards, patients with and without incident fractures were stratified in two age-matched groups with a 1: 2 proportion (Group F' and Group NF', respectively). The performance of REMS T-score in discriminating between the two groups was quantitatively assessed and compared with DXA.1516 patients were enrolled and 1370 completed the follow-up (mean ± SD: 3.7 ± 0.8 years; range: 1.9-5.0 years). Fracture incidence was 14.0%. Age-matched groups included 175 fractured patients and 350 non-fractured ones, respectively (median age 70.2 [interquartile range: 61.0-73.3] and 67.3 [65.4-69.8] years, p-value ns). The groups resulted also balanced for height, weight and BMI (p-values ns). As expected, the differences in REMS T-score (for vertebral site, -2.9 [-3.6 to -1.9] in Group F', -2.2 [-2.9 to -1.2] in Group NF') and DXA T-score (-2.8 [-3.3 to -1.9] in Group F', -2.2 [-2.9 to -1.4] in Group NF') were statistically significant (p-value0.001). Analogous results were obtained for femoral neck. Considering the T-score cut-off of -2.5, REMS identified Group F' patients with a sensitivity of 65.1% and specificity of 57.7% of (OR = 2.6, 95%CI: 1.77-3.76, p 0.001), whereas DXA showed a sensitivity of 57.1% and a specificity of 56.3% (OR = 1.7, 95%CI: 1.20-2.51, p-value = 0.0032). For femoral neck, REMS sensitivity and specificity were 40.2% and 79.9%, respectively, with an OR of 2.81 (95%CI: 1.80-4.39, p 0.001). DXA, instead, showed a sensitivity and specificity of 42.3% and 79.3%, respectively, with an OR of 2.68 (95%CI: 1.71-4.21, p 0.001).REMS T-score resulted an effective predictor for the risk of incident fragility fractures in a population-based sample of female subjects, representing a promising parameter to enhance osteoporosis diagnosis in the clinical routine.

Epidemiological and clinical data have suggested the existence of a relationship between cardiovascular diseases and metabolic bone disease. Several studies have demonstrated that heart valve calcification presents substantial similarities with that of bone. Literature data indicate that there are many active processes which promote osteogenesis and loss of mineralization inhibitors that lead to the deposition of extracellular matrix and proteins of bone tissue in cardiac valves. This review aimed to synthesize the available data in order to allow a better understanding of the relationship between osteoporosis or other metabolic bone diseases, such as primary hyperparathyroidism, and valvular calcification in humans. Electronic databases of Pubmed-Medline, Cochrane Library, and SCOPUS from inception to March 31, 2019 were searched. The full set of the articles potentially eligible were carefully assessed and reviewed. Finally, 23 studies were eligible and included in the systematic review. The majority of studies reported that osteoporosis and/or osteopenia were independent risk factors for valvular calcifications, even after adjusting for common cardiovascular risk factors. This suggests that this relationship is not only due to the presence of common cardiovascular risk factors but rather to underlying biological factors that connect them. Instead, regarding the association between primary hyperparathyroidism and valve calcification, conflicting data were found in the literature. To sum up, most of the literature data confirm that cardiac valve calcification processes are strongly influenced by alterations in bone metabolism. In particular, the patients with osteoporosis or primary hyperparathyroidism have an acceleration in the process of valvular calcification. Additional studies are needed to specifically address the mechanisms by which metabolic bone diseases could influence cardiac valve calcification.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169–521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR 4.1–5.3 log 10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P=0.003): TDR to NRTIs from 9.9 to 2.9% (P=0.003) and TDR to NNRTIs from 5.1 to 3.7% (P=0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P&nbsp

Background/aim In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. Materials and methods Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. Results From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. Conclusion IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control.

In the last decades, protein engineering has developed particularly in biotechnology and pharmaceutical field. In particular, the engineered antibody subclass has arisen. The single chain diabody format (scDb), conjugating small size with antigen specificity, offers versatility representing a gold standard for a variety of applications, spacing from research to diagnostics and therapy. Along with such advantages, comes the challenge of optimizing their production, improving expression systems, purification procedures and stability. All such parameters are detrimental for protein production in general and above all for recombinant antibody expression, which has to be fine-tuned, choosing a proper protein-expression host and adjusting expression protocols accordingly. In the present paper, we present data regarding the production and purification of a single chain diabody directed against the macromolecular complex hERG1/β1 integrin. We focus on the expression of clones deriving from the transformation of Pichia pastoris yeast cells. In particular, we compare two different clones arose from two separate transformation processes, demonstrating that both are suitable for proper protein expression. Moreover, we have set up an expression protocol and compared the yields obtained using two purification machines: Akta Pure and Akta Start, with a positive outcome.

Background Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs) are effective inhibitors of bone resorption and are currently considered the drugs of choice for the prevention and treatment of osteoporosis and related fractures. Data from several publications have suggested that BPs may also be effective in reducing the atherosclerotic process and vascular calcification, but the results of these studies are contrasting. This review aimed to allow a better understanding of the relationships between BPs and atherosclerosis in humans. Materials and methods Electronic databases of Pubmed-Medline, Cochrane Library and SCOPUS from inception to June 30, 2016 were searched. The full texts of the articles potentially eligible were carefully assessed and reviewed. Finally, 20 studies were found to be eligible and were included in the systematic review. All included studies were published between 2000 and 2014. Results In several studies, etidronate limited the progression of aortic and coronary calcification in hemodialysis patients, whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease, kidney trasplant or in those with osteoporosis. Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue, with the consequent release of bone turnover markers and cytokines into the bloodstream. Conclusion To sum up, the BPs seem to have the potential of influencing atherosclerosis and calcium homeostasis at the level of vascular walls with several possible mechanisms which may differ according to the type, potency, dosage and administration route of BPs. Additional studies are needed to specifically address the mechanism by which BP use could influence cardiovascular morbidity and mortality.

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m2 during RT and 200 mg/m2 days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.

Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients' quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm2, 30 mW, illuminated area 0.04 cm2, 7.5 J/cm2, 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head and Neck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p = 0.0012; stimulated: p

Background: Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity. Objectives: The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression. Methods: 212 chronic sarcoidosis patients (mean age 56.07 ± 12 years; 97 males) were retrospectively recruited. Demographic, clinical, functional, and radiological data, and serum-urinary calcium metabolism were entered into an electronical database for analysis. Levels of CTO and angiotensin-converting enzyme (ACE) were measured and bone mineral density and lung function tests were conducted. Results: Hypercalciuria and hypercalcemia were observed in 18.8 and 1.8% of patients, respectively. Urinary calcium levels correlated with CTO activity (r = 0.33, p = 0.0042). Patients with worsening persistent disease showed the highest levels of urinary calcium. Diffusing capacity of the lung for carbon monoxide (DLCO) percentage correlated inversely with urinary calcium (r = 0.1482; p = 0.0397). Conclusions: Calcium metabolism alteration, particularly hypercalciuria, was observed in a significant percentage of patients of sarcoidosis. Urinary calcium was correlated with clinical status, DLCO, and serum CTO activity, suggesting its potential role as a biomarker of the activity and severity of sarcoidosis.

PURPOSE: The purpose of this paper was to review the available approaches for bone strength assessment, osteoporosis diagnosis and fracture risk prediction, and to provide insights into radiofrequency echographic multi spectrometry (REMS), a non-ionizing axial skeleton technique. METHODS: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review the current image-based methods for bone strength assessment and fracture risk estimation, and to discuss the clinical perspectives of REMS. RESULTS: Areal bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the consolidated indicator for osteoporosis diagnosis and fracture risk assessment. A more reliable fracture risk estimation would actually require an improved assessment of bone strength, integrating also bone quality information. Several different approaches have been proposed, including additional DXA-based parameters, quantitative computed tomography, and quantitative ultrasound. Although each of them showed a somewhat improved clinical performance, none satisfied all the requirements for a widespread routine employment, which was typically hindered by unclear clinical usefulness, radiation doses, limited accessibility, or inapplicability to spine and hip, therefore leaving several clinical needs still unmet. REMS is a clinically available technology for osteoporosis diagnosis and fracture risk assessment through the estimation of BMD on the axial skeleton reference sites. Its automatic processing of unfiltered ultrasound signals provides accurate BMD values in view of fracture risk assessment. CONCLUSIONS: New approaches for improved bone strength and fracture risk estimations are needed for a better management of osteoporotic patients. In this context, REMS represents a valuable approach for osteoporosis diagnosis and fracture risk prediction.

Aim: This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG). Patients & methods: The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. Results: We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. Conclusion: The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.