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The improvement of chemotherapy, radiotherapy, and surgical interventions, together with hematopoietic stem cell transplantation, increased childhood cancer survival rate in the last decades, reaching 80% in Europe. Nevertheless, anti-cancer treatments are mainly responsible for the onset of long-term side effects in childhood cancer survivors (CCS), including alterations of the endocrine system function and activity. In particular, the most frequent dysfunction in CCS is a metabolic bone disorder characterized by low bone mineral density (BMD) with increased skeletal fragility. BMD loss is also a consequence of a sedentary lifestyle, malnutrition, and cancer itself could affect BMD, thus inducing osteopenia and osteoporosis. In this paper, we provide an overview of possible causes of bone impairment in CCS in order to propose management strategies for early identification and treatment of skeletal fragility in this population.

In the intraerythrocytic protozoan parasites of the genus Babesia both innate and adaptive immune responses are necessary to confer protection against clinical disease. In particular, the adaptive immune response involves the production of neutralizing antibodies as well as the presentation of parasite antigens to CD4+ T lymphocytes by professional antigen-presenting cells. Therefore, the development of alternative vaccines that replace the use of live attenuated strains should include relevant epitopes targeting both B and T cell responses. The aim of this study was to design new Babesia bigemina immunogens and evaluate the humoral and cellular responses in mice. To achieve this, three B. bigemina recombinant antigens called Apical Membrane Antigen 1 (AMA-1), Rhoptry Associated Protein 1 (RAP-1) and the Thrombospondin Related Anonymous Protein 1 (TRAP-1) were obtained. Besides, two recombinant modified vaccinia virus Ankara vectors coding for chimeric constructs containing bioinformatically predicted B and T cell epitopes from the same three antigens were generated. These immunogens were evaluated in prime-boost heterologous schemes. Among the combinations tested, priming with a cocktail of the three proteins followed by a booster immunization with a mix of both viruses induced the highest activation of IFN-γ+ CD4+ and CD8+ antigen-specific T cell responses. Remarkably, all vaccine schemes containing antigen cocktails also induced antibodies that were capable of neutralizing merozoite invasion of bovine erythrocytes in vitro at a level comparable to an anti B. bigemina hyperimmune bovine serum. Our results offer a new perspective for vaccines against B. bigemina combining bioinformatics predictions and prime-boost immunization regimes for future control measures against bovine babesiosis., (Copyright © 2022. Published by Elsevier GmbH.)

Objective: To investigate the correlations between clinical, functional, and radiological outcomes in inpatients with coronavirus disease 2019 (COVID-19)., Methods: In this observational study, we recruited inpatients affected by moderate COVID-19 disease. The clinical evaluation comprised the Cumulative Illness Rating Scale (CIRS), numerical rating scale (NRS), modified Rankin scale (mRS), and the modified Borg dyspnea scale (mBDS). Respiratory involvement was assessed with computed tomography (CT) and graded with a CT-severity score (CT-SS). We retrospectively assessed functioning using the International Classification of Functioning, Disability and Health (ICF) codes of the Clinical Functioning Information Tool (ClinFIT) COVID-19 in the acute phase. Correlation analysis was performed 1) between clinical, instrumental, and functional parameters and 2) between ICF categories., Results: The data showed statistically significant moderate correlations between CT-SS and the following categories: b152 "emotional functions" and b440 "respiratory functions"., Conclusion: This is the first study to use the ICF framework in people with a moderate form of COVID-19 in the acute phase. Considering the correlations between some ICF categories and radiological findings, our results support the use of the ClinFIT COVID-19 for a comprehensive assessment of COVID-19 patients.

The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs.

Background: Osteoporotic vertebral fractures (OVFs) are often followed by chronic back pain which may have a nociceptive, neuropathic, or mixed component. However, literature on this topic is lacking., Objective: The objective of this cross-sectional study is to characterize the neuropathic component of chronic back pain in patients with OVFs., Methods: Spine fractures were detected by morphometric examination. Pain severity and its impact on activities of daily living (ADL) were evaluated through the Brief Pain Inventory (BPI). Neuropathic pain was investigated through the Italian versions of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS) and the painDETECT questionnaire (PD-Q)., Results: We included 72 patients, mainly women (88.8%), with mean age of 69.2 years. The 70.8% of patients had multiple OVFs, of which 47% located at the thoracic spine, 43.1% at the thoracic and at lumbar spine, and 9.8% at the lumbar spine. The BPI showed moderate back pain in 23.6% of cases and severe in 8.3% of cases, with high interference with ADL in 38.9% of patients. The PD-Q revealed the presence of neuropathic pain in 5.5% of cases, while the LANSS in 23.6% of cases., Conclusions: In our study, the prevalence of neuropathic component of chronic back pain ranged from 5.5% to 23.6%, according to PD-Q and LANSS respectively, in patients with OVFs. Further studies should investigate if the characterization of chronic back pain might contribute to appropriateness of interventions for this population.

Background and Objectives: Complex regional pain syndrome (CRPS) is a chronic condition characterized by disproportionate regional pain, usually affecting distal limbs, that follows trauma or surgery. Athletes may develop CRPS because of exposure to traumatic or overuse injuries. The aim of the present study is to review the available literature about CRPS type 1 in athletes. Materials and Methods : We searched two online databases (PubMed and Web of Science), selecting papers aiming at investigating CRPS type 1 (algodystrophy) in athletes. The analysis of databases was made considering original articles published until 30 June 2021, written in English. Results: Fifteen papers (12 case reports, 3 case series) were selected for a total of 20 clinical cases (15 females, 5 males), aged between 10 and 46 years (mean age 18.4 ± 9.8 standard deviation years). Patients included practiced different types of sport (soccer, athletics, gymnastics, basketball). The most involved anatomical sites were lower limbs, and time to diagnosis ranged from 2 days to 4 years. The most used treatments were pharmacological and physical therapies, but sometimes invasive approaches, as regional nerve, or lumbar sympathetic blocks, were provided. The main assessed outcomes were return to activity and pain. Conclusions : Our review suggests a higher prevalence of CRPS type 1 in younger people and in lower limbs than in general population but confirms the higher prevalence in females. However, the number of studies addressing CRPS in athletes is limited, as well as the number of involved patients, considering that only few and heterogeneous case reports were published about this topic. Moreover, the high prevalence of old studies (only 5 available studies in the last 10 years) might have influenced the choice of both assessment tools and management strategies. Despite these limitations, athletes showing disproportionate pain after sport-related injury should be promptly evaluated and treated through a multidimensional approach to avoid long-term consequences of algodystrophy.

Early osteoarthritis (EOA) still represents a challenge for clinicians. Although there is no consensus on its definition and diagnosis, a prompt therapeutic intervention in the early stages can have a significant impact on function and quality of life. Exercise remains a core treatment for EOA; however, several physical modalities are commonly used in this population. The purpose of this paper is to investigate the role of physical agents in the treatment of EOA. A technical expert panel (TEP) of 8 medical specialists with expertise in physical agent modalities and musculoskeletal conditions performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP searched for evidence of the following physical modalities in the management of EOA: "Electric Stimulation Therapy", "Pulsed Electromagnetic field", "Low-Level Light Therapy", "Laser Therapy", "Magnetic Field Therapy", "Extracorporeal Shockwave Therapy", "Hyperthermia, Induced", "Cryotherapy", "Vibration therapy", "Whole Body Vibration", "Physical Therapy Modalities". We found preclinical and clinical data on transcutaneous electrical nerve stimulation (TENS), extracorporeal shockwave therapy (ESWT), low-intensity pulsed ultrasound (LIPUS), pulsed electromagnetic fields stimulation (PEMF), and whole-body vibration (WBV) for the treatment of knee EOA. We found two clinical studies about TENS and PEMF and six preclinical studies-three about ESWT, one about WBV, one about PEMF, and one about LIPUS. The preclinical studies demonstrated several biological effects on EOA of physical modalities, suggesting potential disease-modifying effects. However, this role should be better investigated in further clinical studies, considering the limited data on the use of these interventions for EOA patients.

Background and Objectives : Sport-related musculoskeletal injuries (MSK-Is) are a common health issue in athletes that can lead to reduced performance. The aim of this scoping review was to synthetize available evidence on injury incidence rates (IIRs), types, and sites that affect the musculoskeletal (MSK) system of adult athletes. Materials and Methods : We performed a scoping review on the Pubmed database limiting our search to 33 Olympic sports. Results : We identified a total of 1022 papers, and of these 162 were examined in full for the purpose of this review. Archery was the sport with the highest risk of injuries to the upper extremities, marathons for the lower extremities, and triathlon and weightlifting for the body bust. In the majority of the sports examined, muscle/tendon strain and ligament sprain were the most common MSK-Is diagnoses, while athletics, karate, and football were the sports with the highest IIRs, depending on the methods used for their calculations. Conclusions : Our scoping review highlighted the general lack and dishomogeneity in the collection of data on MSK-Is in athletes.

Tendinopathy is a complex clinical condition with a rising incidence and prevalence, particularly during sports practice. For the return to play in affected patients, adequate functional and structural recovery of the tendon is the ultimate goal, avoiding the high risk of recurrence. In this perspective, local therapies alongside exercise are showing promising results. Despite evidence suggesting hyaluronic acid (HA) injections as effective in the treatment of tendinopathy, current recommendations about the management of this condition do not include this intervention. HA seems to be an effective therapeutic option for the management of sport-related tendinopathies, but further studies with a larger sample size are needed to confirm available findings. In this narrative review, we analyzed available literature about the rationale of the use of HA in the management of tendon injury and, particularly, in sport-related tendinopathies.

Muscle injuries occur frequently in athletes, accounting for more than one-third of sport-related trauma. Athletes most affected by these injuries are those practicing football and track and field, with hamstrings and gastrocnemius-soleus as the mainly involved sites. Muscle injuries lead to loss of competitions, long recovery times and risk of re-injury with a consequent increase of the management costs. It is therefore advisable to make an accurate and timely diagnosis to establish appropriate interventions for proper healing in the shortest time. In this context, ultrasound imaging is widely used for diagnosis of musculoskeletal disorders because of several advantages including absence of radiation, portability, good spatial resolution, and the ability to perform dynamic tests. The aim of this review is to address the role of US in the evaluation of athletes with muscle injuries. US may play a pivotal role for the management of sport-related muscle injuries because it is fast and relatively cheap, allowing dynamic muscle assessment and time series evaluation of the healing process.

Muscle is one of the main targets for the biological effects of vitamin D. This hormone modulates several functions of skeletal muscles, from development to tissue repair after injury, through genomic and non-genomic mechanisms. Vitamin D deficiency and supplementation seem to significantly affect muscle strength in different populations, including athletes, although optimal serum 25(OH)D3 level for sport performance has not been defined so far. Additionally, vitamin D deficiency results in myopathy characterized by fast-twitch fiber atrophy, fatty infiltration, and fibrosis. However, less is known about regenerative effects of vitamin D supplementation after sport-related muscle injuries. Vitamin D receptor (VDR) is particularly expressed in the embryonic mesoderm during intrauterine life and in satellite cells at all stages of life for recovery of the skeletal muscle after injury. Vitamin D supplementation enhances muscle differentiation, growth, and regeneration by increasing the expression of myogenic factors in satellite cells. The objective of this narrative review is to describe the role of vitamin D in sport-related muscle injury and tissue regeneration.

The role of the endocannabinoid/endovanilloid (EC/EV) system in bone metabolism has recently received attention. Current literature evidences the modulation of osteoclasts and osteoblasts through the activation or inhibition of cannabinoid receptors in various pathological conditions with secondary involvement of bone tissue. However, this role is still unclear in primary bone diseases. Paget's disease of the bone (PDB) could be considered a disease model for analyzing the role of the EC/EV system on osteoclasts (OCs), speculating the potential use of specific agents targeting this system for managing metabolic bone disorders. The aim of the study is to analyze OCs expression of EC/EV system in patients with PDB and to compare OCs activity between this population and healthy people. Finally, we investigate whether specific agents targeting EC/EV systems are able to modulate OCs activity in this metabolic bone disorder. We found a significant increase in cannabinoid receptor type 2 (CB2) protein expression in patients with PDB, compared to healthy controls. Moreover, we found a significant reduction in multi-nucleated tartrate-resistant acid phosphatase (TRAP)-positive OCs and resorption areas after treatment with JWH-133. CB2 could be a molecular target for reducing the activity of OCs in PDB, opening new therapeutic scenarios for the management of this condition.

Background: Health outcomes of older subjects with hip fracture (HF) may be negatively influenced by multiple comorbidities and frailty. An integrated multidisciplinary approach (i.e. the orthogeriatric model) is, therefore, highly recommended, but its implementation in clinical practice suffers from the lack of shared management protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues., Aim: To develop evidence-based recommendations for the orthogeriatric co-management of older subjects with HF., Methods: A 20-member Expert Task Force of geriatricians, orthopaedics, anaesthesiologists, physiatrists, physiotherapists and general practitioners was established to develop evidence-based recommendations for the pre-, peri-, intra- and postoperative care of older in-patients (≥ 65 years) with HF. A modified Delphi approach was used to achieve consensus, and the U.S. Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence., Results: A total of 120 recommendations were proposed, covering 32 clinical topics and concerning preoperative evaluation (11 topics), perioperative (8 topics) and intraoperative (3 topics) management, and postoperative care (10 topics)., Conclusion: These recommendations should ease and promote the multidisciplinary management of older subjects with HF by integrating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Complex regional pain syndrome type I (CRPS I)-or algodystrophy-is a rare disease that usually occurs after a traumatic event. It is characterized by typical clinical findings such as severe and disabling pain disproportionate to the injury, functional limitations, as well as sensory and vasomotor alterations. However, some people do not report any injury associated with algodystrophy onset in personal history. We describe the management of an unusual case of CRPS I which occurred during the long-term follow-up of percutaneous transluminal coronary angioplasty (PTCA) and performed a narrative review of algodystrophy in non-orthopedic surgery. A clinical case of a 44-year-old man with a spontaneous onset of CRPS I of the right ankle is presented. He did not refer to history of any memorable significant trigger event. Approximately 5 months before the onset of clinical manifestations, he received a PTCA via the right femoral approach. We suppose an association between CRPS and this procedure and propose a possible pathophysiologic mechanism. The patient was treated with intramuscular neridronate, which resulted in significant pain relief and improved his quality of life. A comprehensive clinical and instrumental evaluation in patients with CRPS is challenging but mandatory for a correct diagnosis. An extensive analysis of patient history is important for identifying any potential trigger event, including non-orthopedic procedures. Bone scan could have a pivotal role for improving diagnostic sensitivity and specificity in CRPS I. Neridronate was a safe and effective therapeutic approach for this patient, confirming the results of the high-quality evidence available.

(1) Background. Scoliosis is the most common musculoskeletal manifestation of Neurofibromatosis type 1 (NF1), and it might be dystrophic (D) or non-dystrophic (ND) depending on the presence of dysplastic changes of the spine. The aim of our study was to describe the characteristics and natural history of patients with NF1 and scoliosis. (2) Methods. We retrospectively reviewed records from patients with NF1 and scoliosis. Scoliosis was classified as D if at least two dystrophic changes were documented at imaging. (3) Results. Of the 438 patients reviewed, 43 fulfilled inclusion criteria; 17 were classified in D group and 26 in ND. The groups did not differ in age and localization of scoliosis curvature. Surgery was needed more often in D group, but the between-group difference was not significant. Male-to-female ratios of 3:1 and 4:1 were reported in surgically treated NF1 patients with ND and D scoliosis, respectively. (4) Conclusions. Our data suggests independently by the presence of dysplastic changes affecting the spine that males with NF1 are more often affected by scoliosis that requires surgery.

Our study investigates the relationship, in the aging population, between vertebral fractures, spinal alignment, and quality of life. Kyphotic fractures were related to more significant disability and impaired spinopelvic alignment. The spinal malalignment was strongly associated with fractures in the thoracolumbar junction vertebrae and the absence of powerful compensatory mechanisms as thoracic hypokyphosis and lower lumbar hyperlordosis., Introduction: In adult spine deformity (ASD), the sagittal imbalance is defined by the deformity in the sagittal plane that causes the need for greater use of muscle strength to maintain an upright static posture or walking. Fragility vertebral fractures (VF) and ASD are frequent causes of spinal morbidity in the elderly. The prevalence of both ASD and VF increases with aging. Although these two clinical conditions insist on the same population, little is known about the interactions between sagittal imbalance and vertebral fracture (VF) deformity. The aim of our work is to examine the associations between vertebral fractures, sagittal alignment, and their impact on the quality of life scores in elderly patients., Methods: A retrospective cohort study of 110 patients of both sexes, from a spine surgery waiting list, with at least one VF with ≥ 5° of kyphosis and a full-standing X-ray., Independent Variables: the presence of VF with kyphotic deformity ≥ 10°, fracture level, degree of kyphosis (deformity) of the fracture, number of fractures, spinopelvic angular parameters, demographic parameters, and scales of evaluation of the health-related quality of life., Results: A total of 110 patients with mean age 73.8 ± 5.2, of which 70 women (63%) were included in the study. Subjects with at least one VF ≥ 10° presented greater disability and an overall worse sagittal spinal alignment (no VF10° vs VF10°: TPA 21.30 ± 11.5 vs 26.51 ± 12.6, p = 0.041) and more disability (no VF10° vs VF10°: ODI 41.91 ± 16.9 vs 54.67 ± 15.8, p < 0.001) than patients with less degree of vertebral deformity. Significant compensatory mechanisms involved the thoracic area and the lower lumbar region., Conclusion: Kyphotic VFs were associated with severe alterations of sagittal spine alignment and perceived disability. Subjects with sagittal imbalance have a greater degree of deformity in the thoracolumbar junction area. Thoracic hypokyphosis and lower lumbar hyperlordosis are effective compensatory mechanisms in case of lumbar or thoracic fracture, respectively.

Background: Non-Communicable Diseases (NCDs) are leading causes of mortality. These conditions are also known as chronic diseases of long duration and generally slow progression. Physical activity (PA) is a main factor to delay symptoms and consequences of NCDs. In last decades, reduced physical exercise has been observed across all ages. Despite educational campaigns aimed at modifying unhealthy habits, it is difficult to promote healthy lifestyles in general population. Poor interest, lack of motivation, as well as career and family commitments hinder people's participation in regular PA programs. In this study we propose a theoretical person-centred approach to actively involve general population in enhancing their opportunity to perform PA based on personalized needs and targets., Methods: We defined four profiles of baseline PA levels (inactive, moderately inactive, moderately active, and active people) by referring to Metabolic equivalents (METs) based on individual answers to General Practice Physical Activity Questionnaire (GPPAQ)., Results: Based on the answers to the GPPAQ and by computing the related METs for each profile of baseline exercise levels, we developed an innovative person-centered web-based algorithm/function for enhancing and measuring PA participation in community settings. This function can compute evidence-based standardized profiles of participants, personalized goals of PA being functional to the purpose of maintaining or gaining health benefits, as well as the type and duration of PA needed to reach these goals., Conclusion: It might be speculated that this approach would be a reliable method for increasing people's self-efficacy and population adherence to recommended levels of PA. However, this theoretical proposal requires to be implemented in further research.

Introduction: People affected by osteoporosis and fragility fractures often report disability and poor health-related quality of life. Albeit rehabilitation has a crucial role in older people, post-menopausal women and other subjects with high risk of fragility fractures, the rehabilitation perspective has been poorly investigated in the available guidelines for osteoporosis. The aim of this systematic review was to systematically evaluate the quality of guidelines for osteoporosis from a rehabilitation perspective., Evidence Acquisition: On May 2020, we performed a systematic search on medical literature of all guidelines published in the last 10 years on PubMed, Pedro, and international guideline databases. The study selection was based on key terms "exercise," "physical activity" or "rehabilitation." All authors independently assessed the methodological quality through the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, consisting of six domains (scope, stakeholder involvement, rigor and development, clarity of presentation, applicability, editorial independence)., Evidence Synthesis: Out of 331 documents retrieved, a total of 34 guidelines were selected after the screening phases. Twenty (58.8%) high quality guidelines were reported. According to AGREE II instrument, a mean score of 78.1±21.8% was reported for "scope and purpose" domain; for stakeholder involvement, the mean score was 58.1±22.1%; the rigor of development was good (mean score of 61.3±27.3%); for clarity of presentation the mean score was 79.4±20.3%; the applicability was poor (mean score of 30.9±25.2%); for editorial independence the mean score was 75.1±24.6%. Rehabilitation recommendations for osteoporotic patients were reported in 21 (61.8%) of the selected guidelines., Conclusions: This is the first systematic analysis evaluating quality of the guidelines for osteoporosis using AGREE II instrument. Starting from a state of the art of the currently available evidence, we could conclude that therapeutic exercise at moderate to high intensity is encouraged by several guidelines for the management of people with osteoporosis and fragility fractures. More than half of guidelines were of high-quality. However, most guidelines are lacking specific indications about exercise features. This study might support the implementation of a rehabilitation perspective in the guidelines for osteoporotic patients.

The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, mechanisms of action of this drug are not quite clear, particularly in OA. This scoping review is an overview of the biological as well as the clinical role of clodronic acid in OA., Method: A scoping review based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model was performed to characterize the mechanisms of action of IA clodronate in OA and to evaluate its efficacy from a clinical point of view., Results: Several effects of clodronate have been observed in animal models of OA, including depletion of synovial lining cells that results in reduced production of chemokines (IL-1, TNF- α), growth factors (TGF-β, BMP 2/4), and metalloproteases (MMP 2/3/9); prevention of cartilage damage, synovial hyperplasia, and proteoglycans loss; reduction in joint inflammation, joint swelling, and osteophyte formation. From a clinical perspective, patients with knee OA treated with IA clodronate experienced improvements in pain and joint mobility., Conclusion: Clodronate appears to have different mechanisms of action interfering with the pathogenic processes contributing to OA development and progression. This intervention demonstrated positive effects for patients affected by knee OA.

The outbreak of COVID-19 caused by SARS-CoV-2 has spread worldwide with a huge impact on the healthcare system. Compared to the previous coronaviruses-related pandemics, COVID-19 is more transmissible with potential systemic involvement and peculiar neurological manifestations, such as Guillan-Barrè syndrome up to critical illness myopathy, occurring in the intensive care setting. In this clinical scenario, people living with a neuromuscular disease (NMD) represent a vulnerable category with a high risk of a severe course of COVID-19. Moreover, in the NMD population, the management of respiratory and muscular impairments after SARS-CoV-2 infection might be troubling in terms of both pharmacological and rehabilitative approaches. To date, rehabilitation is still an unmet need in this population with several implications on NMD progression with and without SARS-CoV-2 infection. In particular, rehabilitation intervention for patients with NMD after COVID-19 are lacking. Therefore, in the current paper, we analyze the critical issues of COVID-19 on NMDs patients and propose a home-based rehabilitation program targeted for this population after mild to moderate SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liguori, Moretti, Paoletta, Gimigliano and Iolascon.)

Background: In patients with Parkinson disease (PD), severe postural and gait impairments are rarely observed in early stage of disease and non-motor symptoms (NMS) are often overlooked., Objective: This observational study aimed to characterize the impact of non-motor impairments on walking kinematics in early stages PD patients, and to assess the differences of gait parameters and NMS between PD patients with and without mild cognitive impairment (MCI)., Methods: Twenty-six patients with Modified Hoehn and Yahr Scale score≤2 were evaluated for NMS using Kings Parkinson's Pain Scale, Parkinson Fatigue Severity scale, Parkinson Anxiety Scale, Beck Depression Inventory and Epworth Sleepiness Scale, kinematic parameters through an inertial sensor and cognitive performance by a comprehensive neuropsychological battery., Results: Fatigue had a moderate negative correlation with step cadence, and a moderate to strong positive correlation with gait duration, Timed Up and Go (TUG) and TUG Dual Task (p < 0.01). Pain showed positive moderate correlation with gait duration (p < 0.01). Twelve patients resulted affected by MCI and reported significantly worse scores in gait duration, pain and fatigue (p < 0.05). According to cognitive z scores, PD-MCI group showed a moderate negative correlation between visuospatial abilities and fatigue (p < 0.05)., Conclusions: NMS significantly affect walking kinematics whereas a limited role of cognitive status on motor performance occur in the early PD stages.

Introduction: Long-term use of bisphosphonates (BPs) has been associated with a specific type of tensile side femoral stress fracture known as Atypical Femoral Fracture (AFF). Theoretically periprosthetic femoral fractures (PFF) should be excluded from the diagnosis of AFF. However, emerging evidence correlates prolonged BPs use with the occurrence of a type of PFF with an atypical pattern (atypical PFF, APFF). The aim of the present study is to report 3 cases of APFF treated at a single centre., Methods: Clinical and radiographic records of PFF that occurred between January 2016 and August 2018 were retrospectively reviewed. All patients meeting the American Society for Bone and Mineral Research (ASBMR) criteria for definition of PFF were included. Management strategies for APFF and patient outcomes, including fracture healing and hip function (assessed by the Oxford Hip Score [OHS]) were collected., Results: 3 patients in the study period were identified as APFF (1 incomplete, 2 complete). All patients were females with a mean age of 83.3 years. All patients were treated with lateral plating. The application of a contralateral strut allograft resulted in fracture healing in cases of complete fractures. Mean OHS at final follow-up was 34.3., Conclusions: Despite occurring around a hip stem like PFF, APFF had peculiar clinical and radiographic features, making them more similar to AFF. Therefore, the orthopaedic surgeon should also consider the natural history and healing problems associated with AFF prior in order to choose the most appropriate management for APFF.

Introduction: Management of Osteoarthritis (OA) still is a challenge for clinicians. Taking into account a multidisciplinary approach including pharmacological and non-pharmacological treatments, intra-articular (IA) injection could be considered as an effective local therapy. Areas covered This review provides a new perspective of IA treatment going beyond current available IA agents. We describe novel biological targets for developing new IA agents and innovative modalities of delivery systems. Additional topics include predictors of response for a better choice of IA agents for each patient, diagnostic and prognostic role of biomarkers, accuracy of IA injection, and cost-effectiveness of IA injection. Expert opinion IA treatments seem to be very promising for the management of OA. Identifying clinical and biochemical predictive factors could drive clinician to the appropriate therapeutic approach. To date, there is a gap regarding the benefit of IA treatments in the 'real practice' once they have been adopted. However, considering these promising effects of IA approach, several open questions remain not clarified.

Evidence about the characterization of home workers in terms of both work-related outcomes and health issues is lacking. The purpose of this cross-sectional study was to examine the impact of home working on perceived job productivity and satisfaction, work-related stress, and musculoskeletal (MSK) issues. We included 51 mobile workers, collecting data about demographic characteristics, working experience, job productivity, and stress. Job satisfaction was assessed through the Utrecht Work Engagement Scale (UWES), while MSK pain was investigated by the Brief Pain Inventory (BPI) and Fear Avoidance Beliefs Questionnaire (FABQ). Moreover, a home workplace analysis had to be carried out according to current Italian regulations. Participants declared that they were less productive (39.2%) but less stressed (39.2%) and equally satisfied (51%) compared to the time of office working. Regarding MSK disorders, low back pain (LBP) was referred by 41.2% of home workers and neck pain by 23.5% of them. Neck pain worsened in 50% of home workers, while LBP did not exacerbate in 47.6% of cases. Home workers with MSK pain reported a lower job satisfaction. Depending on our data, the home environment seems to be not adequate in the mobile worker population, with an increased risk for mental health and MSK problems, particularly affecting the spine. Addressing these issues can significantly reduce risks for health, thus, improving job productivity and satisfaction and reducing cost.

Background: Transient osteoporosis of the hip (TOH) is a rare and temporary clinical condition characterised by bone marrow edema (BME), severe pain, and functional limitation. It commonly occurs in middle-aged men or in women in the last trimester of pregnancy. TOH usually resolves with conservative therapy but may predispose to hip fracture or progression to avascular necrosis (AVN). Etiology is still unclear, although several pathophysiological mechanisms underpinning this condition has been proposed. We describe the management of an unusual case of TOH occurred in a patient with subclinical hypothyroidism., Case Presentation: A clinical case of a 46-year-old man with severe pain in the left anterior thigh is presented. After a comprehensive clinical and radiological approach, a TOH was diagnosed. Moreover, biochemical assessment suggested the presence of subclinical hypothyroidism. After 3 months of treatment with clodronate, physical therapy and hormone replacement therapy (HRT) a significant improvement of clinical and radiological outcomes was observed., Conclusion: Several pathological conditions have been related to development of TOH. In our case, we suggested for the first time a role of subclinical hypothyroidism as novel contributory factor for the onset of this condition, providing pathophysiological mechanisms and a scientific rationale for pharmacological treatment.

Proximal humeral fractures (PHF) are the third most common non-vertebral fragility fractures after hip and distal radius. It still controversial which treatment might be more appropriate, and surgically treated outcomes depends also on an appropriate technique. In order to clarify surgical indications, tips and pitfall a narrative review was conducted. Pinning, external fixation, plating and internal fixators has each one its advantages and disadvantages. During the procedure an appropriate use of the fixation device and handling of the soft tissue might be associated with better outcomes. Calcar comminution, varus angulation, medial dislocation of the shaft, fracture-dislocation are factors that could lead to choose a replacement. Hemiarthroplasty and reverse total shoulder arthroplasty are the most common prosthesis used in PHF. The restoration of humeral length and tuberosities might lead to an improvement in clinical outcomes and prosthesis survivorship., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Background: Choline is an essential micronutrient with a pivotal role in several metabolic pathways contributing to liver, neurological, and hematological homeostasis. Although choline is commonly administered to improve physical performance, its effects on muscle are still unclear. The aim of this scoping review is to analyze the role of choline on skeletal muscle in terms of biological effects and clinical implications., Methods: A technical expert panel (TEP) of 6 medical specialists with expertise in muscle physiology and skeletal muscle disorders performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP planned a research on PubMed selecting "choline" as MeSH (Medical Subject Headings) term adding to PubMed Search Builder the terms "skeletal muscle" and "muscle striated". TEP considered for eligibility articles published in the last 30 years, including original researches, particularly in vitro studies, and animal and clinical studies in the English language., Results: From the 1239 studies identified, TEP included 14 studies, 3 in vitro, 9 animal, and 2 clinical studies., Conclusions: Our scoping review elucidates and summarizes the crucial role of choline in modulating muscle fat metabolism, muscle proteins homeostasis, and the modulation of inflammation and autophagy.

Hip fractures are severe conditions with a high morbidity and mortality, especially when the diagnosis is delayed, and if formulated over 30 days after the injury, is termed a 'neglected femoral neck fracture' (NFNF).Cerebral palsy (CP) is probably one of the major risk factors for NFNF in Western countries, mainly because of both cognitive and motor impairments. However, considering the high prevalence of fractures in these patients, the incidence of NFNF in this population is probably underestimated, and this condition might result in persistent hip or abdominal pain.Several techniques are available for the treatment of NFNF (i.e. muscle pedicle bone graft, fixation with fibular graft, valgisation osteotomy), but most of them could affect motor function.Motor function must be preserved for as long as possible, in order to enhance the quality of life of CP patients.After discussing published NFNF cases in CP patients and available treatment options, a practical approach is proposed to facilitate the orthopaedic surgeon to both early identify and appropriately manage these challenging fractures. Cite this article: EFORT Open Rev 2020;5:58-64. DOI: 10.1302/2058-5241.5.190019., Competing Interests: ICMJE Conflict of interest statement: GT reports payment for expert testimony, grants/grants pending, and travel/accommodation/meeting expenses unrelated to activities listed, all outside the submitted work. The other authors declare no conflict of interest relevant to this work., (© 2020 The author(s).)

Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients' nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the alveolus after tooth extraction. This scoping review aims to summarize the role of dietary supplements in optimizing osseointegration after implant insertion surgery. A technical expert panel (TEP) of 11 medical specialists with expertise in oral surgery, bone metabolism, nutrition, and orthopedic surgery performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP identified micronutrients from the "European Union (EU) Register of nutrition and health claims made on foods" that have a relationship with bone and tooth health, and planned a PubMed search, selecting micronutrients previously identified as MeSH (Medical Subject Headings) terms and adding to each of them the words "dental implants" and "osseointegration". The TEP identified 19 studies concerning vitamin D, magnesium, resveratrol, vitamin C, a mixture of calcium, magnesium, zinc, and vitamin D, and synthetic bone mineral. However, several micronutrients are non-authorized by the "EU Register on nutrition and health claims" for improving bone and/or tooth health. Our scoping review suggests a limited role of nutraceuticals in promoting osseointegration of dental implants, although, in some cases, such as for vitamin D deficiency, there is a clear link among their deficit, reduced osseointegration, and early implant failure, thus requiring an adequate supplementation.

Neuromuscular diseases (NMDs) are inherited or acquired conditions affecting skeletal muscles, motor nerves, or neuromuscular junctions. Most of them are characterized by a progressive damage of muscle fibers with reduced muscle strength, disability, and poor health-related quality of life of affected patients. In this scenario, skeletal health is usually compromised as a consequence of modified bone-muscle cross-talk including biomechanical and bio-humoral issues, resulting in increased risk of bone fragility and fractures. In addition, NMD patients frequently face nutritional issues, including malnutrition due to feeding disorders and swallowing problems that might affect bone health. Moreover, in these patients, low levels of physical activity or immobility are common and might lead to overweight or obesity that can also interfere with bone strength features. Also, vitamin D deficiency could play a critical role both in the pathogenesis and in the clinical scenario of many NMDs, suggesting that its correction could be useful in maintaining or enhancing bone health, especially in the early phases of NMDs. Last but not least, specific disease-modifying drugs, available for some NMDs, are frequently burdened with adverse effects on bone tissue. For example, glucocorticoid therapy, standard of care for many muscular dystrophies, prolongs long-term survival in treated patients; nevertheless, high dose and/or chronic use of these drugs are a common cause of secondary osteoporosis. This review addresses the current state of knowledge about the factors that play a role in determining bone alterations reported in NMDs, how these factors can modify the biological pathways underlying bone health, and which are the available interventions to manage bone involvement in patients affected by NMDs. Considering the complexity of care of these patients, an interdisciplinary and multimodal management strategy based on both pharmacological and non-pharmacological interventions is recommended, particularly targeting musculoskeletal issues that are closely related to functional independence as well as social implications., (Copyright © 2019 Iolascon, Paoletta, Liguori, Curci and Moretti.)

Background: The International Classification of Functioning, Disability and Health (ICF) Generic-30 Set (previously referred to as Rehabilitation Set) is a minimal set of ICF categories for reporting and assessing functioning and disability in clinical populations with different health conditions along the continuum of care. Recently, the Italian Society of Physical and Rehabilitation Medicine (SIMFER) developed an Italian modification of the simple and intuitive descriptions (SID) of these categories. This study was the first one to implement the use of the SID in practice., Aim: The main aims of this study are: 1) to implement the use of the ICF in clinical practice and research among Italian Residents in PRM, and 2) to verify if the SID made the application of ICF Generic 30 Set more user-friendly than the original descriptions; 3) to examine the prevalence of functioning problems of patients accessing Rehabilitation Services to serve as reference for the development of an ICF-based clinical data collection tool., Design: Multicenter cross-sectional study., Setting: Italian Physical Medicine and Rehabilitation (PRM) outpatient rehabilitation services., Population: Patients referring to Italian PRM outpatient rehabilitation services and Italian Residents in PRM., Methods: Each School of Specialization involved, randomly, received the ICF Generic-30 Set with the original descriptions or with the SID. Residents collected over a 4-month period (April-July 2016) patients data related to the ICF Generic-30 Set categories. Moreover, the residents self-assessed their difficulty in using the ICF Generic-30 Set with the original descriptions or with the SID, through a Numeric Rating Scale (NRS)., Results: Ninety-three residents collected functioning data of 864 patients (mean aged 57.7±19.3) with ICF Generic-30 Set: 304 with the original descriptions and 560 with SID. The difficulty in using the ICF Generic-30 Set with SID was rated as lower than using the original descriptions (NRS 2.8±2.5 vs. 3.5±3.1; P<0.001). The most common disease was the back pain (9.6%) and the most common altered ICF categories were b280 (76.3%) and b710 (72.9%)., Conclusions: This multicenter cross-sectional study shown that the ICF Generic-30 Set is a valuable instrument for reporting and assessing functioning and disability in clinical populations with different health conditions and along the continuum of care and that SID facilitate the understanding of the ICF categories and therefore their use in clinical practice., Clinical Rehabilitation Impact: By increasing the knowledge of ICF among Italian PRM residents, this national survey makes an important step towards the system-wide implementation of ICF in the Italian healthcare system.

Background: Anaplasma marginale is a well-known cattle pathogen of tropical and subtropical world regions. Even though, this obligate intracellular bacterium has been reported in other host species different than bovine, it has never been documented in Myrmecophaga tridactyla (giant anteater) or Hippocamelus antisense (taruca), which are two native endangered species., Methods: Samples from two sick wild animals: a Myrmecophaga tridactyla (blood) and a Hippocamelus antisense (blood and serum) were studied for the presence of A. marginale DNA through msp5 gene fragment amplification. Further characterization was done through MSP1a tandem repeats analysis and MLST scheme and the genetic relationship among previously characterized A. marginale sequences were studied by applying, eBURST algorithm and AMOVA analysis., Results: Anaplasma marginale DNA was identified in the Myrmecophaga tridactyla and Hippocamelus antisense samples. Through molecular markers, we identified an identical genotype in both animals that was not previously reported in bovine host. The analysis through eBURST and AMOVA revealed no differentiation between the taruca/anteater isolate and the bovine group., Conclusions: In the present publication we report the identification of A. marginale DNA in a novel ruminant (Hippocamelus antisense) and non-ruminant (Myrmecophaga tridactyla) host species. Genotyping analysis of isolates demonstrated the close relatedness of the new isolate with the circulation population of A. marginale in livestock. Further analysis is needed to understand whether these two hosts contribute to the anaplasmosis epidemiology.