Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.

INTRODUCTION: Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. METHODS: Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. RESULTS: Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. CONCLUSIONS: A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

The role of bone modifying agents for secondary osteoporosis prevention and pain control in post-menopausal osteopenic breast cancer patients undergoing adjuvant aromatase inhibitors.

Introduction: Hormonal therapy (HT) blocks the hormone-mediated growth signal dramatically reducing estrogenic levels with aromatase inhibitors (AIs) becoming a crucial component of the treatment mainstay in patients with early breast cancer (BC). Postmenopausal BC patients receiving HT present with a significant risk of secondary osteoporosis with AIs further reducing estrogen levels and ultimately leading to an accelerated rate of bone resorption and thus decreased bone mineral density (BMD). This was an observational retrospective clinical study that consecutively enrolled early BC patients with osteopenia to compare the impact of alendronate versus denosumab on secondary osteoporosis prevention and pain control. Methods: We identified two groups of patients treated with denosumab 60 mg by subcutaneous injection once every six months or alendronate 70 mg orally once a week. All the patients underwent a baseline physiatric evaluation (T0) and underwent a follow-up visit after 18 months (T1) together with femoral and vertebral Dual-Energy X-ray Absorptiometry (DEXA) exam evaluating T-Score marks. From September 2015 to December 2019 a total of 50 early (stage I-III) BC patients were considered eligible and consecutively enrolled in our study if they met pre-specified inclusion criteria. Results: In the entire observed population, the addition of treatment with alendronate or denosumab led to a significant T-score improvement at the lumbar spine level (-1.92 vs -1.52, p=0.03), with a comparable contribution from alendronate (-1.60 vs -1.45, p=0.07) and denosumab (-2.26 vs -1.58, p=0.07). Regarding the femoral region, neither alendronate (-0.98 vs -1.07, p=0.23) nor denosumab (-1.39 vs -1.34, p=0.81) were able to produce any statistically relevant effect. However, concerning pain control, BMAs had a significant impact on reducing NRS scoresin the general population (T1 3.94 vs. baseline 4.32, p=0.007), with a likelyspecific contribution from alendronate (T1 3.52 vs. baseline 3.88, p=0.004) compared to denosumab (T1 4.36 vs baseline 4.76, p=0.12), without any differences in analgesic therapy assumption over time (p=0.93). Discussion: Both alendronate and denosumab significantly contributed to preventing secondary osteoporosis in early BC patients with low BMD undergoing AIs, mostly at the lumbar spine level. Moreover, alendronate seemed to significantly impact pain control in such patients further supporting alendronate as a cost-effective option in this frail setting, although BMAs particularities should be carefully considered on an individual basis according to specific clinical contexts.

The Role of Physical Exercise and Rehabilitative Implications in the Process of Nerve Repair in Peripheral Neuropathies: A Systematic Review.

BACKGROUND: The various mechanisms involved in peripheral nerve regeneration, induced by exercise and electrical nerve stimulation, are still unclear. OBJECTIVE: The aim of this review was to summarize the influence of physical exercise and/or electrical stimulation on peripheral nerve repair and regeneration and the variation of impact of intervention depending on timing, as well as kind and dosage of the intervention. A literature survey was conducted on PubMed, Scopus, and Web of Science, between February 2021 to July 2021, with an update in September 2022. METHODOLOGY: The literature search identified 101,386 articles with the keywords: "peripheral nerve" OR "neuropathy" AND "sprouting" OR "neuroapraxia" OR "axonotmesis" OR "neurotmesis" OR "muscle denervation" OR "denervated muscle" AND "rehabilitation" OR "physical activity" OR "physical exercise" OR "activity" OR "electrical stimulation". A total of 60 publications were included. Eligible studies were focused on evaluating the process of nerve repair (biopsy, electromyographic parameters or biomarker outcomes) after electrical stimulation or physical exercise interventions on humans or animals with peripheral sensory or motor nerve injury. SYNTHESIS: This study shows that the literature, especially regarding preclinical research, is mainly in agreement that an early physical program with active exercise and/or electrical stimulation promotes axonal regenerative responses and prevents maladaptive response. This was evaluated by means of changes in electrophysiological recordings of CMAPs for latency amplitude, and the sciatic functional index (SFI). Furthermore, this type of activity can cause an increase in weight and in muscle fiber diameter. Nevertheless, some detrimental effects of exercising and electrical stimulation too early after nerve repair were recorded. CONCLUSION: In most preclinical studies, peripheral neuropathy function was associated with improvements after physical exercise and electrical stimulation. For humans, too little research has been conducted on this topic to reach a complete conclusion. This research supports the need for future studies to test the validity of a possible rehabilitation treatment in humans in cases of peripheral neuropathy to help nerve sprouting.

Rehabilitation approach in robot assisted total knee arthroplasty: an observational study.

BACKGROUND: The purpose of this study is to evaluate the impact of total knee arthroplasty (TKA) with the aid of Navio Robot, comparing it with standard prosthetic surgery on the functional outcomes of patients after an intensive rehabilitation program. METHOD: A case-control observational study was conducted on patients undergoing TKA for severe KOA. All patients underwent the same intensive hospital rehabilitation program of 14 daily sessions lasting 3 h. The following rating scales were administered: Numeric Rating Scale (NRS), Knee Society Score (KSS) and 12-Item Short Form Survey scale. Patient assessments were performed 1 week post-surgery (T0), 1 month post-surgery (T2), and 3 months post-surgery (T3). The primary outcomes were active knee extension and flexion and pain severity. The secondary outcomes were functional capacity and quality of life. RESULTS: Using repeated measures ANOVA, we observed at T1 a statistically different difference for the treatment group compared to the control group about KSS (p < 0.05), pain (p < 0.05), and knee flexion (p < 0.05). No statistically significant difference between the two groups was observed for knee extension (p = 0.09) and the SF-12 scale (p = 0.52). At T2 instead, we observed a statistically significant difference for the treatment group compared to the control group as regards KSS (p < 0.05) and knee flexion (p < 0.05), while no statistically significant difference was observed for pain (p = 0.83), knee extension (p = 0.60), and the SF-12 scale (0.44). CONCLUSIONS: Our study has demonstrated that robot-NAVIO assisted knee prosthesis surgery, associated with a specific intensive rehabilitation treatment, in the short and medium term, determines good pain control, better flexion recovery and a improvement of functional capacity.

Early Denosumab for the prevention of osteoporotic fractures in breast cancer women undergoing aromatase inhibitors: A case-control retrospective study.

BACKGROUND: Aromatase inhibitors (AIs) might have a detrimental impact on bone health in breast cancer (BC) women. Denosumab has been shown to reduce the risk of fractures, but the appropriate time for starting is yet to be clearly defined. OBJECTIVE: To evaluate the effects of early treatment with Denosumab (⩽ 12 months after starting AIs) compared to a delayed treatment in BC women. METHODS: In this retrospective case-control study, we included medical records of BC post-menopausal women, treated with AIs therapy; they were divided as: study group (starting Denosumab ⩽ 12 months after AIs) and control group (> 12 months). At the baseline (T0) and at 18 months (T1), we evaluated the lumbar spine (LS) Tscore and femoral neck (FN) Tscore. Furthermore, at T1 we assessed the incident fragility fractures. RESULTS: Fifty-nine BC survivors (mean age: 61.5 ± 11.5 years) were included: 28 with Early Denosumab and 31 with Late Denosumab. At T1, the study group did not show any incident hip or vertebral fragility fracture, whereas the Late Denosumab group showed 2 incident hip fractures (6.5%) and 4 (12.9%) vertebral fragility fractures. Early Denosumab showed a significant positive effect on both LS (p= 0.044) and FN (p= 0.024) Tscore variations. CONCLUSION: Taken together, our findings suggest that an early start of Denosumab might be considered for the osteoporosis management in BC women undergoing AIs.

Attitudes toward the SARS-CoV-2 and Influenza Vaccination in the Metropolitan Cities of Bologna and Palermo, Italy.

Vaccine hesitancy (VH) is known to play a relevant role in thwarting the efforts toward reaching satisfactory influenza vaccination coverage, and has caused similar difficulties during the COVID-19 pandemic. This study aims to describe the phenomenon and produce insights on the reasons behind VH. A survey was administered between December 2020 and February 2021 to adults living in the cities of Bologna and Palermo. Of the 443 subjects enrolled, 47.3% were likely to get the influenza vaccination, while 75.6% were willing to receive the COVID-19 vaccination. The most frequent determinants that motivated the willingness to get the COVID-19 vaccine were trust in the safety of vaccines and belief that the vaccine is an effective tool. As for people's unwillingness to be vaccinated, being exposed to information that produced doubts about the vaccine and lack of trust in a newly developed vaccine were the most frequently involved determinants. Statistically significant positive associations were found between the willingness to be vaccinated and postgraduate education and the propensity towards influenza vaccination. A negative association with being over 40 years old and of female gender was also found. These results might have an impact in better understanding individual reasons behind VH, identifying which categories are more exposed to it and which strategies should be implemented.

Adolescent idiopathic scoliosis screening: Could a school-based assessment protocol be useful for an early diagnosis?

BACKGROUND: Adolescent idiopathic scoliosis screening still needs a considerable implementation, particularly throughout a school-based assessment protocol. OBJECTIVE: This study aims to evaluate the effectiveness of clinical examinations currently in use for the diagnosis of adolescent idiopathic scoliosis, through a survey carried out in secondary schools to standardize a screening protocol that could be generalized. METHODS: In their classrooms, the adolescents underwent an idiopathic scoliosis screening through three examinations: Adam's test, axial trunk rotation (ATR) and plumb line. In case of single positivity to one of the three examinations, a column X-ray examination was recommended. RESULTS: The sensitivity and diagnostic specificity of Adam's test or ATR were 56.3% and 92.7%, respectively. The positivity to at least one between ATR or plumb line showed that sensitivity was higher than specificity: 91.3% versus 80.8%; the positivity to at least one between Adams's test or plumb line showed a sensitivity of 95.2% and a specificity of 81.5%. Finally, the positivity to all three examinations showed an increase in specificity (99.7%). CONCLUSIONS: Taken together, our findings show that this school-based screening protocol had a very high specificity in early diagnosis of adolescent idiopathic scoliosis.

An Integrated Pharmacophore/Docking/3D-QSAR Approach to Screening a Large Library of Products in Search of Future Botulinum Neurotoxin A Inhibitors.

Botulinum toxins are neurotoxins produced by Clostridium botulinum. This toxin can be lethal for humans as a cause of botulism; however, in small doses, the same toxin is used to treat different conditions. Even if the therapeutic doses are effective and safe, the adverse reactions could be local and could unmask a subclinical impairment of neuromuscular transmissions. There are not many cases of adverse events in the literature; however, it is possible that sometimes they do not occur as they are transient and, if they do occur, there is no possibility of a cure other than to wait for the pharmacological effect to end. Inhibition of botulinum neurotoxin type A (BoNT/A) effects is a strategy for treating botulism as it can provide an effective post-exposure remedy. In this paper, 13,592,287 compounds were screened through a pharmacophore filter, a 3D-QSAR model, and a virtual screening; then, the compounds with the best affinity were selected. Molecular dynamics simulation studies on the first four compounds predicted to be the most active were conducted to verify that the poses foreseen by the docking were stable. This approach allowed us to identify compounds with a calculated inhibitory activity in the range of 316-500 nM.

A Systematic Review of Pharmacologic and Rehabilitative Treatment of Small Fiber Neuropathies.

The aim of this systematic review is to guide the physician in defining the pharmacologic and rehabilitative therapeutic approaches for adopting the best strategies described in the current literature. The search was conducted in PubMed, EMBASE, Cochrane Library and Web of Science to identify the treatment of small fiber neuropathies. Two reviewers independently reviewed and came to a consensus on which articles met inclusion/exclusion criteria. The authors excluded the duplicates, animal studies and included the English articles in which the treatment of patients with small fiber neuropathies was described. The search identified a total of 975 articles with the keywords "small fiber neuropathy" AND "rehabilitation" OR "therapy" OR "treatment". Seventy-eight selected full-text were analyzed by the reviewers. Forty-two publications met the inclusion criteria and were included in the systematic review to describe the rehabilitative and pharmacologic treatment of small fiber neuropathies. Despite the range of different protocols of treatment for small fiber neuropathy, other robust trials are needed. In addition, always different therapeutic approaches are used; a unique protocol could be important for the clinicians. More research is needed to build evidence for the best strategy and to delineate a definitive therapeutic protocol.

The effectiveness of intra-articular injections of Hyalubrix® combined with exercise therapy in the treatment of hip osteoarthritis.

PURPOSE: Osteoarthritis (OA) is the most common joint disorder in the elderly, causing significant pain which negatively affects mobility and quality of life. The aim of the study was to assess the effectiveness of ultrasound image-guided intra-articular injections of Hyalubrix® combined with exercise therapy in the treatment of hip osteoarthritis. METHODS: This was a single site, prospective, open-label, Investigator-initiated study. Forty patients were enrolled and received three ultrasound image-guided injections of Hyalubrix®, 45 days apart, combined with three sessions a week of physical therapy (proprioceptive rehabilitation of the lower limbs; gait training; balance training) up to a total of 30 sessions (10 weeks), starting from one week after the first injection. RESULTS: The primary objective was to achieve a lasting reduction in OA symptoms related to pain during activity. During the course of the study the pain perceived by the patient during activity dropped from a mean value of 6.94 cm to a mean value of 1.46 cm and showed a statistically significant decrease from visit 1 compared to baseline (p < 0.05) which was confirmed at all the subsequent time points. Significant improvements were also observed in the evaluation of the secondary objectives: hip disability; OA-related pain at rest; daily functioning and NSAIDs intake. CONCLUSIONS: Results from this study including 40 patients for a total of 65 treated hips demonstrate a significant improvement in OA-related pain, hip disability, and patient's daily functioning as well as a reduction in NSAIDs intake. Patients suffering from hip OA seem to benefit from the treatment with Hyalubrix® injections plus exercise therapy.

Femoral neck's fracture in Fahr's Syndrome: case report.

Fahr's syndrome, also known as "Bilateral Striopallidodentate Calcinosis" (BSPDC) primitive, is a rare neurological disease characterized by the presence of idiopathic, bilateral, symmetrical and abnormal deposition of calcium in areas of the brain that control movements including the basal ganglia, dentate nuclei of the cerebellum, nuclei of thalamus and semi-oval center. We describe a case of a 76-year-old male patient underwent reduction and fixation of a subtrochanteric fracture with intramedullary nail. During post-operative rehabilitation therapists's patient management was difficult due to obvious extrapyramidal symptoms characterized by dysarthria, rigidity, bradykinesia, postural instability. A CT scan, performed for the onset of stiffness and confusion before the operation, showed: IV ventricle eumorphic and in axis; expansion in atrophic sense of supratentorial ventricular system; bilateral, diffuse and coarse calcifications of the basal ganglia in the cerebellar and occipital cortex, elements compatible with Fahr's syndrome. The patient presented repeated postural instability episodes in the upright position, with loss balance tendency and recurrent falls. Fahr's syndrome patient is a "weak" patient, which requires a multi-disciplinary approach in order to prevent the mobility reduction, to improve the condition of postural instability, thus reducing the risk of fractures using preventive measures in domestic environment.

Physical exercise and sarcopenia in older people: position paper of the Italian Society of Orthopaedics and Medicine (OrtoMed).

Sarcopenia is the age-associated loss of skeletal muscle mass and function. It is a major clinical problem for older people and research in understanding of pathogenesis, clinical consequences, management, and socioeconomic burden of this condition is growing exponentially. The causes of sarcopenia are multifactorial, including inflammation, insulin resistance, changing endocrine function, chronic diseases, nutritional deficiencies and low levels of physical activity. Operational definition of sarcopenia combines assessment of muscle mass, muscle strength and physical performance. The diagnosis of sarcopenia should be based on having a low appendicular fat free mass in combination with low handgrip strength or poor physical functioning. Imaging techniques used for estimating lean body mass are computed tomography, magnetic resonance imaging, bioelectrical impedance analysis and dual energy X-ray absorptiometry, the latter considered as the preferred method in research and clinical use. Pharmacological interventions have shown limited efficacy in counteracting the age-related skeletal muscle wasting. Recent evidence suggests physical activity and exercise, in particular resistance training, as effective intervention strategies to slow down sarcopenia. The Italian Society of Orthopaedics and Medicine (Or-toMed) provides this position paper to present the update on the role of exercise on sarcopenia in the elderly.

The burden of previous fractures in hip fracture patients. The Break Study.

A positive history of fractures in older patients with hip fracture is common. We determined the risk factors associated with a positive history of fractures and the profile of care in hip fracture patients. In the Break Study, we enrolled 1249 women aged ≥60 years, seeking care for a hip fracture. Baseline information included age, body mass index, lifestyle (smoking habit, alcohol consumption), patient's history of fracture after the age of 50 years, family history of fragility fracture and health status (presence of comorbidity, use of specific drugs, pre-fracture walking ability, type of fracture, time to surgery, type of surgery, osteoporosis treatment). In the multivariable model age, smoking, family history, treatment with antiplatelet, anticoagulants and anticonvulsants, were significant predictors of a positive history of fracture. More than 70% of patients underwent surgery more than 48 hours after admission. About 50% were discharged with a treatment for osteoporosis, but more than 30% only with calcium and vitamin D. In conclusion, factors associated with a positive history of fracture are the traditional risk factors, suggesting that they continue to have a negative impact on health even at older ages. Selected drugs, such as antiplatelet and anticoagulants, deserve further consideration as significant factors associated with fractures. Given that delay in surgery is a major cause of mortality and disability, while treatment for osteoporosis decreases significantly the risk of recurrent fractures and disability, interventions to modify these patterns of care are urgently needed.