Personalizing Cancer Pain Therapy: Insights from the Rational Use of Analgesics (RUA) Group

Introduction: A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current guidelines and clinical practice with a lack of consensus on items regarding the use of strong opioids in treating cancer pain. Those results represented the basis for a new Delphi study addressing a better approach to pain treatment in patients with cancer. Methods: The study consisted of a two-round multidisciplinary Delphi study. Specialists rated their agreement with a set of 17 statements using a 5-point Likert scale (0 = totally disagree and 4 = totally agree). Consensus on a statement was achieved if the median consensus score (MCS) (expressed as value at which at least 50% of participants agreed) was at least 4 and the interquartile range (IQR) was 3–4. Results: This survey included input from 186 palliative care specialists representing all Italian territory. Consensus was reached on seven statements. More than 70% of participants agreed with the use of low dose of strong opioids in moderate pain treatment and valued transdermal route as an effective option when the oral route is not available. There was strong consensus on the importance of knowing opioid pharmacokinetics for therapy personalization and on identifying immediate-release opioids as key for tailoring therapy to patients’ needs. Limited agreement was reached on items regarding breakthrough pain and the management of opioid-induced bowel dysfunction. Conclusion: These findings may assist clinicians in applying clinical evidence to routine care settings and call for a reappraisal of current pain treatment recommendations with the final aim of optimizing the clinical use of strong opioids in patients with cancer

Three-Dimensional Craniofacial Bone Reconstruction With SmartBone on Demand

This is a report of a 34-year-old male lacking of bone development in the frontal and orbital part of the skull due to a surgical removal of a right orbital-front osteoma at the age of 5. The integrity of the craniofacial district was important for the young patient also for social acceptance and self-esteem.Based on computed tomography patient images, a skull model was reconstructed, both digitally and on 3-dimensional real model, to best design the needed bone graft. Defect wide extension and surface curvature called for the use of the puzzle technique, where the whole graft is composed by several elements, mechanically slotting into each other. The realization was made possible thanks to the use of a composite xenohybrid bone substitute specifically developed for reconstructive surgery (SmartBone, by Industrie Biomediche Insubri SA). SmartBone technology allowed the realization of custom-made grafts which perfectly joined each other and fitted the bone defect thanks to mechanical strength, also at low thicknesses and wide extensions.The postoperative course was uneventful and computed tomography scans showed new bone formation and complete calvaria continuity already 10 months after surgery, with no signs of inflammation over the entire follow-up.This case study represents a proof of concept that SmartBone on Demand custom-made bone grafts, together with puzzle technique, are effective, easy to handle and provide final excellent functional and aesthetic results

Growth and flowering of miltonia flavescens lindl. var. stellata regel orchid under different doses of a slow release fertilizer

The Orchidaceae is one of the most numerous and diversified families in the Plant Kingdom. Miltonia flavescens Lindl. is a native orchid to the southern region of Brazil. Studies related to the nutrition and fertilization of orchids are scarce, specific and existent only for few species. The objective of this work was to evaluate the effect of different doses of a slow release fertilizer (Osmocote (R) 9/15/12 + micro) on the development of M. flavescens var. stellata Regel cultivated in pots with pine bark and coconut fiber (1:1, v:v) as the substrate. The treatments consisted of: no fertilizer application (control), application of 2.5 g, 5 g and 10 g of fertilizer per liter of substrate. The experimental design was set in randomized blocks, with five replications and three plants per plot. The experiment was carried out along 25 months and the fertilizer was applied every five months. The evaluated plant parameters were: length of the longest pseudobulb, number of pseudobulbs, diameter of pseudobulbs, number of shoots, number of leaves and flowering. There was a significant increment on all evaluated characteristics with the increase of the fertilizer dose. The highest dose provided a more profuse flowering, with a larger number of flower stems and flowers, in addition to bigger flower stems and flowers. These results show that the supply of nutrients in an appropriate amount is of a great importance for the development and flowering of M. flavescens

Imbalance of osteoclastogenesis regulating factors in patients with celiac disease

Celiac disease is an autoimmune disorder characterized by atrophy of the intestine villi triggered by ingestion of gluten in genetically susceptible individuals. The association between celiac disease and low BMD has been recognized, but the mechanisms of disturbance are poorly understood. We show imbalance of cytokines relevant to bone metabolism in celiac patients' sera and the direct effect of these sera on in vitro bone cell activity. Introduction: Celiac disease is associated with mineral metabolism derangement and low BMD. We investigated whether imbalance of serum factors in celiac patients could affect human bone cell activity in vitro. Materials and Methods: We studied two groups of celiac patients - one on a gluten-free diet and another before the diet - both with decreased bone mass. Patients were investigated for bone turnover markers, and their sera were used for culturing bone cells from healthy donors and evaluate changes in cell activity. Results: The N-terminal telopeptide of procollagen type I and interleukin (IL)-6 were higher than normal in patients not on the gluten-free diet. IL-1\u3b2 and TNF-\u3b1/\u3b2 were normal in all patients. IL-12 was reduced in all patients, whereas IL-18 was reduced only in patients on the diet. The RANKL/osteoprotegerin (OPG) ratio was increased in patients not on the gluten-free diet. Persistently increased osteoclast numbers were obtained from peripheral blood mononuclear cells of healthy donors on incubation with sera of patients not on the gluten-free diet versus control sera and sera from patients on the diet. In human osteoblasts from healthy individuals, IL-18 was reduced on incubation with sera from all patients, whereas OPG expression was lower when sera from patients not on the diet were used. Proliferation, alkaline phosphatase, and nodule mineralization were increased in osteoblast cultures containing sera from all celiac patients, either on or not on the gluten-free diet. Conclusions: We conclude that bone loss in celiac disease might also be caused by a cytokine imbalance directly affecting osteoclastogenesis and osteoblast activity