Peripheral artery disease: an underdiagnosed condition in familial hypercholesterolemia? A systematic review.

PURPOSE: Familial hypercholesterolemia (FH) is one of the most common inherited diseases characterized by elevated LDL-cholesterol levels, leading to early-onset atherosclerosis. While the association between FH and coronary and carotid artery disease is well-established, its association with peripheral artery disease (PAD) is less robust. This systematic review aims at exploring existing evidence on PAD prevalence and incidence in FH individuals. METHODS: A comprehensive search was conducted on MEDLINE and Embase databases, for studies published between January 2013 and December 2023, evaluating prevalence and incidence of PAD in FH patients. Literature reviews, case reports, responses to editors and non-English language articles were excluded. RESULTS: The initial research provided 53 results. After article screening, 28 articles were fully reviewed and 24 were finally included in the analysis. Among these, 19 reported PAD prevalence, while 5 PAD incidence over a mean follow-up time of 8.7 years. PAD prevalence and incidence ranged from 0.3 to 60% and from 0.5 to 4.2% respectively, probably reflecting the heterogeneity in PAD definition criteria. CONCLUSION: This systematic review sheds light on the limited number of studies on PAD in FH patients. Particularly, considering the potential positive effects of newly available lipid-lowering strategies on PAD outcomes, addressing this research gap is pivotal for a more comprehensive understanding of peripheral vascular manifestations in FH patients and for optimal management of this population.

Overview of Cochrane Systematic Reviews for Rehabilitation Interventions in Individuals with Upper Limb Fractures: A Mapping Synthesis.

Background and Objectives. This overview of Cochrane systematic reviews (CSRs) reports on current evidence on the effectiveness of rehabilitation interventions for persons with upper limb fractures (ULFs), and the quality of the evidence. Materials and Methods. Following the inclusion criteria defined by the World Health Organization, all CSRs tagged in the Cochrane Rehabilitation database that were relevant for persons with ULFs were included. A mapping synthesis was used to group outcomes and comparisons of included CSRs, indicating the effect of rehabilitation interventions and the certainty of evidence. Results. A total of three CSRs were included in the evidence map. The certainty of evidence was judged as low to very low. Early occupational and hand therapy, cyclic pneumatic soft tissue compression, and cross-education, when started during immobilization, may improve grip strength and wrist range of motion, with results maintained up to 12 weeks from the cast removal, compared to no intervention. Approaches such as occupational therapy and passive mobilisation, started post-immobilization, are probably safe in terms of secondary complications. However, the overall evidence of rehabilitative interventions related to proximal humeral fractures has been judged insufficient for all the outcomes considered. A paucity of primary studies and CSRs for elbow fractures was noted. Conclusions. This overview provided the effect and the certainty of evidence of rehabilitation interventions available after ULFs using a mapping synthesis. To date, there is a need to further the effectiveness and safety of these interventions for persons with ULFs, improving methodological quality of the research in the field.

Bone involvement in the early stages of Parkinson's disease: a case-control study.

OBJECTIVE: To evaluate the qualitative and quantitative alterations of bone tissue in patients with early-stage Parkinson's disease (PD) and to measure the associations between bone mineral density (BMD), trabecular bone score (TBS) and physical performance. METHODS: This case-control study enrolled patients with early-stage PD and age-matched controls. BMDs for the left femoral neck (L-FN) and lumbar spine (LS) were measured. Bone microarchitecture for the LS was determined using TBS. Muscle performance was assessed using the short physical performance battery (SPPB). Patients and controls were stratified in two groups based on the SPPB score: a poor performance group (SPPB score ≤8) and high performance group (SPPB > 8). RESULTS: This study included 26 patients: 13 in the PD group and 13 age-matched controls. The mean ± SD BMD results in the PD group were: L1-L4 BMD = 0.935 ± 0.183 g/cm2; L-FN BMD = 0.825 ± 0.037 g/cm2; with bone microarchitecture degraded in four patients and partially degraded in three patients. TBS was significantly different in the patients with PD stratified according to SPPB. Among the controls, there was a significant difference in body mass index between the two SPPB groups. CONCLUSION: TBS might identify bone involvement earlier than BMD in the initial stages of PD.

Characterization of an Italian population with neurological disorders in a rehabilitation setting using ClinFIT.

OBJECTIVE: To examine the functioning profile of people with neurological disorders who access rehabilitation services through ClinFIT Generic-30. METHODS: The functioning profile of people with neurological disorders accessing rehabilitation services was examined using the ClinFIT Generic-30, and the results compared with existing core set (neurological health conditions acute and post-acute,stroke, Multiple Sclerosis, Traumatic Brain Injury,Spinal Cord Injury). RESULTS: Data for 364 people were analysed. The 10 most commonly impaired ICF categories included 3 for Body Functions (exercise tolerance functions (b455), mobility of joint functions (b710), and muscle power functions (b730)) and 7 for Activities and Participation (carrying out daily routine (d230), handling stress and other psychological demands (d240), changing basic body position (d410), maintaining a body position (d415), transferring oneself (d420), walking (d450), and moving around (d455)), while the ICF categories that were severely impaired (ICF qualifiers 3 and 4) in more than 30% of the study cohort were: muscle power functions (b730), carrying out daily routine (d230), walking (d450), moving around (d455), doing housework (d640), and assisting others (d660). DISCUSSION: The current study data suggests that  ClinFIT Generic-30 appears to effectively identify impairments and/or restrictions, as perceived by individuals affected by selected health conditions. CONCLUSION: ClinFIT Generic-30 is a tool that can be used to characterize functioning profile in people with different neurological disorders and to collect important information not addressed by the disease-specific core sets (neurological health conditions acute and post-acute,stroke, Multiple Sclerosis, Traumatic Brain Injury,Spinal Cord Injury).

The role of the fracture liaison service in the prevention of atypical femoral fractures.

Osteoporosis and fragility fractures (FFs) are considered critical health problems by the World Health Organization (WHO) because of high morbidity, mortality, and healthcare costs. The occurrence of a FF raises the risk of a subsequent fracture (refracture). The hip is the most common site of fragility refracture, and its onset is associated with a further increase in patient's morbidity, mortality, and socioeconomic burden. Therefore, the prevention of refracture is essential. In this context, fracture liaison service (FLS) demonstrated to be able to reduce FF risk and also improve patients' adherence to anti-osteoporotic treatments, particularly for bisphosphonates (BPs). However, long-term and high adherence to BPs may lead to atypical femoral fractures (AFFs). These latter are tensile side stress fractures of the femur, with high rates of complications, including delayed and non-healing. An effective FLS should be able to prevent both FF and AFF. A comprehensive and interdisciplinary approach, through the involvement and education of a dedicated team of healthcare professionals (i.e. orthopedic, geriatrician, primary care physician, rehabilitation team, and bone nurse) for evaluating both FF and AFF risks might be useful to improve the standard of care.

Anti-sclerostin antibodies: a new frontier in fragility fractures treatment.

Bone fragility is the determinant of the increased risk of minimal trauma fracture and must be treated with a multimodal approach that includes pharmacological therapy, physical exercise, and adequate nutrition. Pharmacological therapy, to date based on the administration of antiresorptive drugs, such as bisphosphonates and denosumab, or osteoanabolic drugs, such as teriparatide and abaloparatide, has shown to be effective in reducing the risk of fracture in osteoporotic patients. In the context of the cellular and molecular mechanisms that regulate bone metabolism, the discovery of the Wnt signaling pathway and its role in bone tissue homeostasis has allowed the identification of sclerostin as an inhibitor of osteoblastic activity and simultaneously as a stimulator of osteoclastic activity. Therefore, the use of a monoclonal antibody, romosozumab, against this protein has been tested as a potential drug with a dual action, stimulating bone neo-apposition and inhibiting bone resorption. The efficacy of romosozumab has been demonstrated in numerous clinical trials against both placebo and other drugs commonly used in the treatment of patients affected by osteoporosis. The advantages of this drug lie above all in its rapid action which makes it particularly suitable in clinical situations where it is necessary to improve bone strength very quickly due to the imminent risk of fragility fracture. Clinical studies and guidelines suggest romosozumab as an initial drug in an ideal sequential approach from osteoanabolic to antiresorptive drugs. Some aspects of cardiovascular safety remain to be fully investigated, therefore its use in osteoporotic patients at high cardiovascular risk should be avoided until further data become available.

New insights in lower limb reconstruction strategies.

High Energy Musculoskeletal Traumas (HEMTs) represent a relevant problem for healthcare systems, considering the high social costs, and both the high morbidity and mortality. The poor outcomes associated with HEMT are related to the high incidence of complications, including bone infection, fracture malunion and non-union. The treatment of each of these complications could be extremely difficult. Limb reconstruction often needs multiple procedures, rising some questions on the opportunity in perseverate to try to save the affected limb. In fact, theoretically, amputation may guarantee better function and lower complications. However, amputation is not free of complication, and a high long-term social cost has been reported. A comprehensive literature review was performed to suggest possible ways to optimize the limb preservation surgeries of HEMT's complications in order to ameliorate their management.

What are the benefits and harms of physical activity on irritable bowel syndrome? - A Cochrane Review summary with commentary.

The aim of this commentary is to discuss from a rehabilitation perspective the Cochrane Review "Physical activity for treatment of irritable bowel syndrome"(1) by Nunan D.[1], published by Cochrane Gut Group. This Cochrane Corner is produced in agreement with Journal of Rehabilitation Medicine by Cochrane Rehabilitation with views* of the review summary author in the "implications for practice" section. [1] This summary is based on a Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2022, Issue 6, Art. No.: CD011497, DOI: 10.1002/14651858.CD011497.pub2 (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review. * The views expressed in the summary with commentary are those of the Cochrane Corner author (different than the original Cochrane Review authors) and do not represent the Cochrane Library or Medical Journals Sweden or Journal of Rehabilitation Medicine.

Pain and Motor Function in Myotonic Dystrophy Type 1: A Cross-Sectional Study.

Pain is an underestimated finding in myotonic dystrophy type 1 (DM1). We provide a characterization of pain in terms of functional implications through a multidimensional assessment in patients with DM1, focusing on gender differences. We assessed pain through the Brief Pain Inventory (BPI) and its indexes (the Severity Index (SI) and the Interference Index (II)), balance/gait (the Tinetti Performance-Oriented Mobility Assessment (POMA)), functional abilities (the Functional Independence Measure (FIM)), and fatigue (the Fatigue Severity Scale (FSS)). We divided our sample into a mild (<4) and a moderate-severe group (≥4) based on BPI indexes. A between-group analysis was performed. We recruited 23 males and 22 females with DM1. A statistically significant difference was found for the FSS and the BPI-SI ≥ 4, and for all outcomes in the BPI-II ≥ 4 (p ≤ 0.003). In the female group, all outcomes except for the FIM were statistically significantly worse (p ≤ 0.004). Dividing our sample into four groups based on gender and the BPI, a statistically significant difference was found for FSS between the two groups with BPI-II ≥ 4 (with worsen score in the female one) (p < 0.002). Pain in DM1 patients is highly reported and gender related, with increased fatigue and poor balance/gait in the female group.

Overview of Cochrane systematic reviews for rehabilitation interventions in individuals with cerebral palsy: A mapping synthesis.

AIM: This overview of Cochrane systematic reviews (CSRs) reports on current evidence on the effectiveness of rehabilitation interventions for individuals with cerebral palsy (CP) and the quality of the evidence. METHOD: Following the inclusion criteria defined by the World Health Organization, all CSRs tagged in the Cochrane Rehabilitation database that were relevant for individuals with CP were included. A mapping synthesis was used to group outcomes and comparisons of included CSRs indicating the effect of rehabilitation interventions and the certainty of evidence. RESULTS: A total of eight CSRs were included in the evidence map. The effect of interventions varied across comparisons and the certainty of evidence was inconsistent, ranging from high to very low. The best evidence was found for botulinum neurotoxin A (BoNT-A) combined with occupational therapy in the management of spasticity. However, the effect of BoNT-A on drooling and salivation remains unclear. A paucity of randomized controlled trials studying treatments for both dystonia and postural deformities was noted. INTERPRETATION: This review emphasizes the need to further investigate the effectiveness and cost-benefit of rehabilitation interventions for individuals with CP. WHAT THIS PAPER ADDS: The quality and quantity of evidence on rehabilitation interventions for cerebral palsy is limited worldwide. Botulinum neurotoxin A plus occupational therapy showed robust efficacy for the management of upper-limb spasticity. Evidence on sleep-positioning systems for hip migration and trihexyphenidyl for dystonia is scarce.

Bone fragility during the COVID-19 pandemic: the role of macro- and micronutrients.

Bone fragility is the susceptibility to fracture due to poor bone strength. This condition is usually associated with aging, comorbidities, disability, poor quality of life, and increased mortality. International guidelines for the management of patients with bone fragility include a nutritional approach, mainly aiming at optimal protein, calcium, and vitamin D intakes. Several biomechanical features of the skeleton, such as bone mineral density (BMD), trabecular and cortical microarchitecture, seem to be positively influenced by micro- and macronutrient intake. Patients with major fragility fractures are usually poor consumers of dairy products, fruit, and vegetables as well as of nutrients modulating gut microbiota. The COVID-19 pandemic has further aggravated the health status of patients with skeletal fragility, also in terms of unhealthy dietary patterns that might adversely affect bone health. In this narrative review, we discuss the role of macro- and micronutrients in patients with bone fragility during the COVID-19 pandemic.

Which interventions are effective for promoting physical activity in people with neuromuscular disease? A Cochrane Review summary with commentary.

BACKGROUND: Neuromuscular diseases (NMDs) are conditions characterized by progressive muscle weakness resulting in limitations in the activities of daily living. Physical inactivity in this population represents a major health issue increasing the risk of further chronic health problems and complications. OBJECTIVE: To discuss evidence on the effects of intervention for promoting physical activity in people with NMDs from a rehabilitative perspective. METHODS: To summarize and comment on the published Cochrane Review "Interventions for promoting physical activity in people with neuromuscular disease" by Jones et al. RESULTS: This Cochrane Review included 13 trials (795 participants from 12 studies, number of participants unclear in one study) evaluating practical, informational, or motivational interventions, designed to promote physical activity, in comparison to no intervention, or another intervention. CONCLUSION: A low- to very-low certainty of the evidence was found on the effectiveness of physical activity-promoting interventions in people with NMD. Further studies are required to address this topic.

Bone fragility: conceptual framework, therapeutic implications, and COVID-19-related issues.

Bone fragility is the susceptibility to fracture even for common loads because of structural, architectural, or material alterations of bone tissue that result in poor bone strength. In osteoporosis, quantitative and qualitative changes in density, geometry, and micro-architecture modify the internal stress state predisposing to fragility fractures. Bone fragility substantially depends on the structural behavior related to the size and shape of the bone characterized by different responses in the load-deformation curve and on the material behavior that reflects the intrinsic material properties of the bone itself, such as yield and fatigue. From a clinical perspective, the measurement of bone density by DXA remains the gold standard for defining the risk of fragility fracture in all population groups. However, non-quantitative parameters, such as macro-architecture, geometry, tissue material properties, and microcracks accumulation can modify the bone's mechanical strength. This review provides an overview of the role of different contributors to bone fragility and how these factors might be influenced by the use of anti-osteoporotic drugs and by the COVID-19 pandemic.

Osteosarcopenia and type 2 diabetes mellitus in post-menopausal women: a case-control study.

Background: Osteosarcopenia has been defined as the concomitance of low bone density (osteopenia/osteoporosis) and sarcopenia. Osteoporosis is characterized by alterations in bone microarchitecture and decrease of bone mineral density (BMD), whereas sarcopenia is the progressive decrease of both muscle mass and function that increase the risk of falls. Type 2 diabetes mellitus (T2DM) is associated with poor bone strength and muscle wasting. Objective: The aim of this study is to analyze the association between osteosarcopenia and T2DM in post-menopausal women (PMW). Methods: We performed an age matched case-control study (1:2 ratio), considering as cases PMW affected by T2DM, and PMW without T2DM as control group. For all patients a DXA evaluation to investigate bone density and body composition measures were performed. Moreover, we carried out muscle strength and performance assessments. Outcome measures were femoral neck and lumbar spine BMD T-scores, appendicular lean mass (ALM), handgrip strength and the Short Physical Performance Battery (SPPB). Data from both groups were analyzed and compared. Results: Thirty-six PMW (12 T2DM vs 24 non-T2DM) were recruited. The frequency of osteosarcopenia was significantly higher in the T2DM group compared to controls (50% vs 17%; OR 5.0, 95% CI 1.05 to 23.79, p = 0.043). Handgrip strength was significantly lower in the T2DM group (10.09 ± 4.02 kg vs 18.40 ± 6.83 kg; p = 0.001). Conclusions: Post-menopausal women with T2DM have a 5 times higher risk to have osteosarcopenia compared to non-diabetic ones. Further studies on larger cohorts are required to confirm these findings.

Functioning issues in inpatients affected by COVID-19-related moderate pulmonary impairment: a real-practice observational study.

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.

Efficacy and Effectiveness of Extracorporeal Shockwave Therapy in Patients with Myofascial Pain or Fibromyalgia: A Scoping Review.

Myofascial pain syndrome (MPS) and fibromyalgia (FM) are underestimated painful musculoskeletal conditions that could impact function and quality of life. A consensus about the most appropriate therapeutic approach is still not reached. Considering the long course of the diseases, prolonged assumption of drugs, such as NSAIDs and pain killers, could increase the risk of adverse events, often leading affected patients and physicians to prefer non-pharmacological approaches. Among these, radial and focused extracorporeal shock waves therapies (ESWT) are widely used in the management of painful musculoskeletal conditions, despite the fact that the mechanisms of action in the context of pain modulation should be further clarified. We performed a scoping review on PubMed using Mesh terms for analyzing the current evidence about the efficacy and effectiveness of ESWT for patients with MPS or FM. We included 19 clinical studies (randomized controlled trials and observational studies); 12 used radial ESWT, and 7 used focused ESWT for MPS. Qualitative analysis suggests a beneficial role of ESWT for improving clinical and functional outcomes in people with MPS, whereas no evidence was found for FM. Considering this research gap, we finally suggested a therapeutic protocol for this latter condition according to the most recent diagnostic criteria.

Characterization of neuropathic component of back pain in patients with osteoporotic vertebral fractures.

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.

Effectiveness of Neridronate in the Management of Bone Loss in Patients with Duchenne Muscular Dystrophy: Results from a Pilot Study.

INTRODUCTION: Bone loss is a major issue in patients affected by Duchenne muscular dystrophy (DMD), a rare musculoskeletal disorder, particularly in those treated with glucocorticoids (GCs). We aimed to assess the effectiveness of neridronate in terms of bone mineral density (BMD) changes in this population. METHODS: We retrospectively reviewed the records of patients affected by DMD receiving GCs referred to our outpatient from 2015 to 2020. All patients were treated with an intramuscular (IM) injection of neridronate (25 mg every month). Bone density was measured at the lumbar spine (LS; L1-L4 tract) using dual-energy x-ray absorptiometry (DXA) (GE Lunar), no more than 4 weeks before (T0) and after 1 year from neridronate treatment (T1). RESULTS: Eight boys with DMD were included with a mean age at diagnosis of 4.75 ± 2.81 years. Six of them were non-ambulant and two of them had previous low-trauma fractures (a distal femur fracture and a vertebral compression fracture, respectively). All patients were receiving deflazacort [median duration of therapy 11.5 years (interquartile range 2-25)]. At the DXA evaluation (T0), the mean L1-L4 BMD value was 0.716 ± 0.164 g/cm2. Six patients (75%) showed an L1-L4 Z-score height-adjusted of less than - 2. The mean age of neridronate initiation was 18.87 ± 6.81 years. All patients were supplemented with calcium carbonate and vitamin D at baseline. After 12 months of treatment (T1), the mean L1-L4 BMD value was 0.685 ± 0.190 g/cm2. Seven patients (87.5%) showed an L1-L4 Z-score of less than - 2. Changes in LS BMD and Z-score were not significant between T0 and T1 in our cohort (p = 0.674 and p = 0.208, respectively) as well as among non-ambulant patients with DMD without previous fragility fractures. CONCLUSIONS: In this study, we reported for the first time that neridronate may slow bone loss in GC-treated patients with DMD at 1-year follow-up.