Ascorbic acid reduces Ropivacaine-induced myotoxicity in cultured human osteoporotic skeletal muscle cells

Background: Osteoporosis is a worldwide health issue. Loss of bone mass is a potential risk factor for fragility fractures, and osteoporotic fractures place a considerable burden on society. Bone and muscle represent a functional unit in which the two tissues are intimately interconnected. Ropivacaine is a potent local anesthetic used in clinical practice for intraoperative anesthesia and postoperative pain management, in particular for hip surgery. When injected, Ropivacaine can diffuse locally through, in particular in surrounding skeletal muscle tissue, causing dose-dependent cytotoxicity, oxidative stress and myogenesis impairment. Based on those evidences, we focused our attention on Ropivacaine-induced cytotoxicity on cultured human myoblasts. Methods: Primary human myoblasts and myotubes from healthy subjects, osteoarthritic and osteoporotic patients (OP) were cultured in the presence of Ropivacaine. In some experiments, ascorbic acid (AsA) was added as a potent antioxidant agent. Cell viability and ROS levels were evaluated to investigate the myotoxic activity and Real-Time PCR and Western blot analysis carried out to investigate the expression of proliferation and myogenic markers. Results: A dose-dependent decrease of cell viability was observed after Ropivacaine exposure in both OP myoblasts and myotubes cultures, whereas those effects were not observed in the presence of Propofol, a general anesthetic. The adding of AsA reduced Ropivacaine negative effects in OP myoblast cultures. In addition, Ropivacaine exposure also increased ROS levels and upregulated Nox4 expression, an enzyme primarily implicated in skeletal muscle ROS generation. AsA treatment counteracted the oxidant activity of Ropivacaine and partially restored the basal condition in cultures. Positive myogenic markers, such as MyoD and Myf5, were downregulated by Ropivacaine exposure, whereas myostatin, a negative regulator of muscle growth and differentiation, was upregulated. The phenotypic deregulation of myogenic controllers in the presence of Ropivacaine was counteracted by AsA treatment. Conclusions: Our findings highlight the oxidative stress-mediated myotoxic effect of Ropivacaine on human skeletal muscle tissue cell cultures, and suggest treatment with AsA as valid strategy to mitigate its negative effects and allowing an ameliorated functional skeletal muscle recovery in patients undergoing hip replacement surgery for osteoporotic bone fracture

I.S.Mu.L.T - Rotator cuff tears guidelines

Despite the high level achieved in the field of shoulder surgery, a global consensus on rotator cuff tears management is lacking. This work is divided into two main sessions: in the first, we set questions about hot topics involved in the rotator cuff tears, from the etiopathogenesis to the surgical treatment. In the second, we answered these questions by mentioning Evidence Based Medicine. The aim of the present work is to provide easily accessible guidelines: they could be considered as recommendations for a good clinical practice developed through a process of systematic review of the literature and expert opinion, in order to improve the quality of care and rationalize the use of resources

Unraveling the impact of upfront chemotherapy and proton beam therapy on treatment outcome and follow-up in central nervous system germ cell tumors: a single center experience

BackgroundGerm cell tumors (GCT) account for a minority of central nervous system (CNS) malignancies, highly prevalent in adolescents and young adults. Despite their aggressive biological behavior, prognosis is excellent in most cases with risk stratified treatment, consisting in a combination of chemotherapy and radiotherapy. Whole ventricular irradiation (WVI) and craniospinal irradiation, the treatment of choice for localized and metastatic disease, pose significant risk of collateral effects, therefore proton beam radiation (PBT) has been recently proposed for its steep dose fallout.Materials and methodsWe report our experience in a consecutive series of 17 patients treated for CNS GCT at our Institution from 2015 to 2021.ResultsMost frequent lesion location were sellar/suprasellar (35%) and bifocal germinoma (35%), followed by pineal (18%) and thalamic (12%). Two patients (12%), had evidence of disseminated disease at the time of diagnosis. At the latest follow-up all but one patient showed complete response to treatment. The only relapse was successfully rescued by additional chemotherapy and PBT. PBT was well tolerated in all cases. No visual, neurological or endocrinological worsening was documented during and after treatment. Neuropsychological evaluation demonstrated preservation of cognitive performance after PBT treatment.ConclusionsOur data, albeit preliminary, strongly support the favourable therapeutic profile of PBT for the treatment of CNS germ cell tumors

On the lookout for influenza viruses in Italy during the 2021-2022 season: along came A(H3N2) viruses with a new phylogenetic makeup of their hemagglutinin

Aims: To assess influenza viruses (IVs) circulation and to evaluate A(H3N2) molecular evolution during the 2021-2022 season in Italy. Materials and methods: 12,393 respiratory specimens (nasopharyngeal swabs or broncho-alveolar lavages) collected from in/outpatients with influenza illness in the period spanning from January 1, 2022 (week 2022-01) to May 31, 2022 (week 2022-22) were analysed to identify IV genome and molecularly characterized by 12 laboratories throughout Italy. A(H3N2) evolution was studied by conducting an in-depth phylogenetic analysis of the hemagglutinin (HA) gene sequences. The predicted vaccine efficacy (pVE) of vaccine strain against circulating A(H3N2) viruses was estimated using the sequence-based Pepitope model. Results: The overall IV-positive rate was 7.2% (894/12,393), all were IV type A. Almost all IV-A (846/894; 94.6%) were H3N2 that circulated in Italy with a clear epidemic trend, with 10% positivity rate threshold crossed for six consecutive weeks from week 2022-11 to week 2022-16. According to the phylogenetic analysis of a subset of A(H3N2) strains (n=161), the study HA sequences were distributed into five different genetic clusters, all of them belonging to the clade 3C.2a, sub-clade 3C.2a1 and the genetic subgroup 3C.2a1b.2a.2. The selective pressure analysis of A(H3N2) sequences showed evidence of diversifying selection particularly in the amino acid position 156. The comparison between the predicted amino acid sequence of the 2021-2022 vaccine strain (A/Cambodia/e0826360/2020) and the study strains revealed 65 mutations in 59 HA amino acid positions, including the substitution H156S and Y159N in antigenic site B, within major antigenic sites adjacent to the receptor-binding site, suggesting the presence of drifted strains. According to the sequence-based Pepitope model, antigenic site B was the dominant antigenic site and the p(VE) against circulating A(H3N2) viruses was estimated to be -28.9%. Discussion and conclusion: After a long period of very low IV activity since public health control measures have been introduced to face COVID-19 pandemic, along came A(H3N2) with a new phylogenetic makeup. Although the delayed 2021-2022 influenza season in Italy was characterized by a significant reduction of the width of the epidemic curve and in the intensity of the influenza activity compared to historical data, a marked genetic diversity of circulating A(H3N2) strains was observed. The identification of the H156S and Y159N substitutions within the main antigenic sites of the most of sequences also suggested the circulation of drifted variants with respect to the 2021-2022 vaccine strain. Molecular surveillance plays a critical role in the influenza surveillance architecture and it has to be strengthened also at local level to timely assess vaccine effectiveness and detect novel strains with potential impact on public health

I.S.Mu.L.T. Achilles Tendon Ruptures Guidelines

This work provides easily accessible guidelines for the diagnosis, treatment and rehabilitation of Achilles tendon ruptures. These guidelines could be considered as recommendations for good clinical practice developed through a process of systematic review of the literature and expert opinion, to improve the quality of care for the individual patient and rationalize the use of resources. This work is divided into two sessions: 1) questions about hot topics; 2) answers to the questions following Evidence Based Medicine principles. Despite the frequency of the pathology andthe high level of satisfaction achieved in treatment of Achilles tendon ruptures, a global consensus is lacking. In fact, there is not a uniform treatment and rehabilitation protocol used for Achilles tendon ruptures

Influence of thyroid hormones on tendon homeostasis

Tendinopathies have a multifactorial etiology driven by extrinsic and intrinsic factors. Recent studies have elucidated the importance of thyroid hormones in the alteration of tendons homeostasis and in the failure of tendon healing after injury. The effects of thyroid hormones are mediated by receptors (TR)-α and –β that seem to be ubiquitous. In particular, T3 and T4 play an antiapoptotic role on tenocytes, causing an increase in vital tenocytes isolated from tendons in vitro and a reduction of apoptotic ones; they are also able to influence extra cellular matrix proteins secretion in vitro from tenocytes, enhancing collagen production. From a clinical point of view, disorders of thyroid function have been investigated only for rotator cuff calcific tendinopathy and tears. In this complex scenario, further research is needed to clarify the role of thyroid hormones on the onset of tendinopathies

Augmentation in fragility fractures, bone of contention: a systematic review

Abstract Background Osteoporosis is a complex multifactorial disease characterized by reduced bone mass and microarchitectural deterioration of bone tissue linked to an increase of fracture risk. Fragility fractures occur in osteoporotic subjects due to low-energy trauma. Osteoporotic patients are a challenge regarding the correct surgical planning, as it can include fixation augmentation techniques to reach a more stable anchorage of the implant, possibly lowering re-intervention rate and in-hospital stay. Methods The PubMed database and the Google Scholar search engine were used to identify articles on all augmentation techniques and their association with fragility fractures until January 2022. In total, we selected 40 articles that included studies focusing on humerus, hip, spine, and tibia. Results Literature review showed a quantity of materials that can be used for reconstruction of bone defects in fragility fractures in different anatomic locations, with good results over the stability and strength of the implant anchorage, when compared to non-augmented fractures. Conclusion Nowadays there are no recommendations and no consensus about the use of augmentation techniques in osteoporotic fractures. Our literature review points at implementing the use of bone augmentation techniques with a specific indication for elderly patients with comminuted fractures and poor bone quality

Hip replacement in femoral neck fractures: the role of cementation and its technical difficulties

Hip fractures in elderly patients are an arising problem due to aging of population and still represent a controversial challenge for orthopedic surgeon who should help achieve the best functional recovery in the shortest time. Cementation in hip replacement plays an important role, but it should be carefully planned considering the possible risks. According to the literature, there are still no certainties regarding the superiority of an uncemented implant compared to a cemented one. The purpose of this work is to conduct an overview of the scientific literature that can clarify the advantages and disadvantages of cemented and non-cemented implants from a biological and biomechanical point of view

Hormones and tendinopathies: The current evidence

BACKGROUND: Tendinopathies negatively affect the quality of life of millions of people, but we still do not know the factors involved in the development of tendon conditions. SOURCES OF DATA: Published articles in English in PubMed and Google Scholar up to June 2015 about hormonal influence on tendinopathies onset. One hundred and two papers were included following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. AREAS OF AGREEMENT: In vitro and in vivo, tenocytes showed changes in their morphology and in their functional properties according to hormonal imbalances. AREAS OF CONTROVERSY: Genetic pattern, sex, age and comorbidities can influence the hormonal effect on tendons. GROWING POINTS: The increasing prevalence of metabolic disorders prompts to investigate the possible connection between metabolic problems and musculoskeletal diseases. AREAS TIMELY FOR DEVELOPING RESEARCH: The influence of hormones on tendon structure and metabolism needs to be further investigated. If found to be significant, multidisciplinary preventive and therapeutic strategies should then be developed

Methylation of the Vitamin D Receptor Gene in Human Disorders

the vitamin D receptor (VDR) mediates the actions of 1,25-Dihydroxvitamin D3 (1,25(OH)2D3), which has important roles in bone homeostasis, growth/differentiation of cells, immune functions, and reduction of inflammation. emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. this review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer, and others. the reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases