Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS ® ) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis.

Growing evidence has shown the promise of mesenchymal stromal cells (MSCs) for the treatment of cutaneous wound healing. We have previously demonstrated that MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp., Plainsboro, NJ) enriched with platelet-rich plasma (Ematrix) have enhanced proliferative potential in vitro as compared with those cultured on the scaffold alone. In this study, we extended the experimentation by evaluating the efficacy of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in vivo. It was found that the presence of MSCs within the scaffolds greatly ameliorated the quality of regenerated skin, reduced collagen deposition, enhanced reepithelization, increased neo-angiogenesis, and promoted a greater return of hair follicles and sebaceous glands. The mechanisms involved in these beneficial effects were likely related to the ability of MSCs to release paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in fact, up-regulated matrix metalloproteinase 9 expression in the extracellular matrix and enhanced the recruitment of endogenous progenitors during tissue repair. In conclusion, the results of this study provide evidence that the treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the recreation of a suitable microenvironment for promoting tissue repair/regeneration at the implantation sites.Bone marrow-derived mesenchymal stromal cells (MSCs) generate great expectation in the field of regenerative medicine due to the easy isolation and expansion, unique antiinflammatory and immune-modulatory properties, and their potential multipotency.

Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases.

significant changes to society. It has changed the way people behave and how healthcare is provided. In our study, we seek to evaluate the impact of the pandemic on the epidemiology of burns in the paediatric population. Government-implemented lockdown measures and school closures have led to reduced outdoor activities and lifestyle changes. Our regional Paediatric Burns Centre introduced a new standard operating protocol involving a new phone consultation pathway, a secure email platform for effective communication with parents and tertiary referring hospitals. The aim is to reduce physical attendance to hospital where possible, streamline our referral service, avoid unnecessary admissions and empower parents where appropriate. We performed a retrospective comparison over five weeks in which the government imposed lockdown instructions from 23/3/2020 to 30/04/2020 (lockdown period) and compared it to a similar period from a year ago 23/03/2019 to 30/04/2019 (control period). During this period, the total attendance to our Emergency Department (ED) has decreased by 60% in the lockdown period (7127 versus 2936), as expected due to the national advice to avoid unnecessary visits to hospital. The incidence of burn injuries reported was instead greater in proportion-2.8% of all ED attendances, compared to 1.5% in the previous year, despite the overall decrease in total number of burn injuries (n = 83) by 24%. This could be due to a combination of the closure of some local and minor injury facilities, reduced faceto-face consultations with general practitioners and the advice given to the general public that even minor burn injuries still require medical attention for adequate treatment. This instruction is crucial for the well-known potentially lifethreatening complications of burns in children [1]. Concerns were raised by the Royal College of Paediatrics and Child Health that children may be coming to harm from delayed presentation to emergency departments for fears of contracting COVID-19 in hospital. In our cohort of burns patients, only 2 were deemed to have come to harm by delaying presentation. We also noted that the number of referrals to children social care increased from 4% (5/123) in the control period to 12% (12/ 95) in the lockdown period. The reduced opportunity to liaise with allied health professionals and education settings to share information and concerns and to finally agree on a plan for follow up might have been due to a more vigilant approach for the fear of missing child protection concerns. The mean age of patients presenting with burns increased from 2.9 to 4.8 years. School-age children are now spending more time at home due to school closures, and UK statistics have suggested that most burns happen at home [2]. Gender distribution is similar in both periods. The number of inpatients in our centre decreased by 37%. All patients required COVID-19 testing prior to admission to

The infection of a wound is one of the major contributors to delays in healing and tissue regeneration. As multi-drug resistance to antibiotics is becoming a serious threat, research in this field has focused on finding new agents and strategies to fight infection and additionally to reduce healing times. The topical use of autologous Platelet Rich Plasma (PRP) as a biological accelerator of the healing process, has been safely used as a form of treatment for wounds since the 1990s. Although the presence or absence of leucocytes in PRP preparation was previously neglected, in the last decade more attention has been paid to their role and several studies have been conducted to explore both their immuno-metabolic effects and their antimicrobial properties. In this review, we aim to summarise the literature on the contribution of leucocytes included in PRP preparations in terms of their antimicrobial properties. This should help to inform clinical practice and additional research in this promising field.

Associated urological anomalies occur commonly in patients with high grade VUR. Our data shows that nearly half of the patients with VUR and associated urological anomalies have renal scarring. Early recognition and treatment of VUR patients with associated urological anomalies may decrease the risk of renal parenchymal damage.

Abstract. The effects of acute administration of haloperidol (4 mg im) and pimozide (4 mg orally) on TSH and Prl secretion were studied in normal and hypothyroid man. The TRH-induced TSH secretion before and after pre-medication with pimozide and domperidone, a peripheral dopamine (DA) blocker, was also evaluated in a group of normal subjects. Haloperidol and pimozide induced a marked increment in serum Prl; mean Prl levels were still significantly elevated 12 h following pimozide administration. A small but significant TSH increase was observed following haloperidol and pimozide in normal as well as hypothyroid subjects. Both domperidone and pimozide significantly enhanced TRH-induced TSH release. In another experiment 3 women with primary thyroid failure received an infusion of DA (4 (μg/kg/min for 4 h) with and without domperidone administration. TSH and Prl levels were suppressed by DA, but the effect was completely abolished by domperidone. The results suggest that psychotrophic drugs, such as haloperidol and pimozide, can, like substituted benzamides, stimulate TSH release in man. Since domperidone and DA do not cross the blood-brain-barrier and domperidone significantly enhanced the TSH response to TRH, the data also support the hypothesis that human TSH is regulated by DA at the hypothalamus (median eminence) and/or pituitary level.

Objective To evaluate the incidence of febrile urinary tract infection (UTI) after successful endoscopic correction of intermediate and high-grade vesicoureteral reflux (VUR).Study design Medical records of 1271 consecutive children (male, 411; female, 903) who underwent successful endoscopic correction of VUR were reviewed. Factors potentially influencing postoperative UTIs, such as history of presentation, age, sex, grade of VUR, renal scarring, and agent used for the endoscopic injection, were analyzed.Results Febrile UTI developed in 73 children (5.7%) after successful endoscopic correction of VUR. Thirty-nine children had a single episode of UTI, and 34 children had two or more episodes at 1 month to 5.9 years (median, 1 year) after correction of VUR. With multivariate analysis, female sex (P < .001), history of preoperative bladder/ bowel dysfunction (BBD; P = .005), and BBD after endoscopic correction (P = .001) were revealed to be the most important independent risk factors for a febrile UTI after successful correction of VUR. ConclusionsThe incidence of febrile UTIs after successful correction of intermediate and high grade VUR is low.Female sex and BBD were the most important risk factors in the development of febrile UTI. Our data supports the importance of assessing bladder and bowel habits in older children with febrile UTIs after endoscopic correction of VUR. (J Pediatr 2012;-:---).V esicoureteral reflux (VUR) is the most common urinary tract abnormality in pediatrics, occurring in 1% to 2% of children, including 30% to 40% of children with urinary tract infection (UTI). 1,2 The association of VUR, febrile UTI, and renal parenchymal damage is well recognized. Reflux nephropathy is a cause of childhood hypertension and chronic renal failure. 3 Marra et al reviewed data on children with chronic renal failure who had high-grade VUR in the Italkid project, a database of Italian children with chronic renal failure, and found that those with VUR accounted for 26% of all children with chronic renal failure. The various treatment options currently available for VUR are: (1) long term antibiotic prophylaxis; (2) open surgical treatment; (3) minimally invasive endoscopic treatment; and (4) observation or intermittent therapy with management of bladder/bowel dysfunction (BBD) and treatment of UTI as they occur.Since United States Food and Drug administration approval in 2001 of dextranomer hyaluronic acid (Dx/HA) as a tissue augmenting substance for subureteral injection, endoscopic treatment has become a widely accepted minimally invasive alternative in the management of VUR.The main goals of treatment of children with VUR are to prevent renal parenchymal damage and morbidity associated with recurrent febrile UTIs. Relatively few studies have examined the incidence of febrile UTIs after successful resolution of VUR with endoscopic injection. The duration of follow-up in most series has been short, with conflicting rates of incidence of UTI. Febrile UTIs after successful resolution of VUR have been reported a...