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INTRODUCTION: Many surgical approaches have been described for hip hemiarthroplasty (HHA) treating femur neck fractures (FNFs). Direct lateral approach (DLA) is one of the most used. Today, the direct anterior approach (DAA) has become very attractive, but it seems to involve more intra-operative fractures. Our main endpoint was to demonstrate that the DAA may be a valid alternative comparing to the DLA. MATERIALS AND METHODS: Patients affected by FNFs and treated with HHA between the years 2016 and 2020 were studied. We divided the treatment of the fractures according to the surgical approach. The analysis was focused on perioperative complications and radiological outcomes. RESULTS: There were a total of 166 patients. The DLA group included patients with an average age of 83.5 years and the DAA group of 83 years. We found similar surgical times (DLA 67 min vs DAA 61 min; p = 0,55), number of transfusions (DLA 3/person vs DAA 4/person; p = 0,91), perioperative complications (fractures: DLA 0 vs DAA 0 – dislocations: DLA 2,50% vs DAA 0) and functional outcomes (HHS: DLA 83 points vs DAA 87 points; p = 0,71). There were no statistical differences comparing diaphyseal filling (Canal Fill Index at the proximal third: DLA 0,79 vs DAA 0,78; p= 0,24), bone loss (Paprosky I: DLA 96,25% vs DAA 91,86%; p = 0,47) and prevalence of heterotopic ossification (Broker low degree: DLA 93,75% vs 95, 34%; p = 0,87). CONCLUSION: Analysing perioperative complications and studying post-operative radiographic evolution, our results suggest that the DAA is a valid alternative to the DLA in HHA treating FNFs.

The COVID-19 pandemic management has led to a significant change in orthopedic surgical activity. During the pandemic, femur fractures in patients over 65 years of age have maintained a constant incidence. Our study will focus on this fragile population, analyzing the incidence of SARS-CoV-2 infection during hospital stays and the clinical and radiographic orthopedic outcomes. We also evaluated the va\riation of COVID-19 infection after health professionals' vaccinations, and the influence of inter-hospital transfers caused by logistical and organizational aspects of the pandemic. Material and Methods: This is a descriptive and prospective study from 13 October 2020 to 15 March 2021. Participants were patients over 65 years of age with diagnoses of proximal femoral fractures with r surgical treatments indicated. We compared the SARS-CoV-2 infected patients during the stay with non-infected cases. A second evaluation was carried out dividing the patients into those who underwent inter-hospital transfers and a group without transfers. We subdivided the study period into two, according to the percentage of healthcare workers vaccinated against SARS-CoV-2. The reported clinical variables included the Parker and Palmer Score, the Nottingham Hip Fracture Score, the Harris Hip Score, mortality, the Rush Score, and evaluation of reduction in radio-lucent lines in prosthetic implants. Results : Ninety-three patients were studied. The whole positive COVID cohort (11.83%) was hospitalized during the period when less than 80% of health workers were vaccinated ( p = 0.02). The COVID cohort and the patients transferred before surgery had longer stays in the Emergency Room ( p = 0.019; p = 0.00007) and longer lengths of stay compared to the other patients ( p = 0.00001; p = 0.001). Mortality was higher both in the infected group and in the patients who underwent a transfer before the surgical procedure (18.18% vs. 1.22 %; p = 0.003. 25% vs. 6.85%; p = 0.02). In terms of orthopedic outcomes measured through the third month of follow-up, we found worse score results in functional and radiographic outcomes in the COVID positive cohort and in the transferred patients' cohort. Conclusions : The impact of the COVID-19 pandemic on patients treated for proximal femur fracture was statistically significant. Patients with Coronavirus during hospitalization obtained poor short-term radiographic and functional results and increased peri-operative mortality. The incidence of intra-hospital infection was high during the period in which health professionals were not yet covered by the anti-COVID vaccination cycle. Patients who were transferred between two hospitals due to pandemic-related management issues also achieved reduced outcomes compared to non-transferred cases, with increased mortality.

In leiomyosarcoma class IIa HDACs (histone deacetylases) bind MEF2 and convert these transcription factors into repressors to sustain proliferation. Disruption of this complex with small molecules should antagonize cancer growth. NKL54, a PAOA (pimeloylanilide o-aminoanilide) derivative, binds a hydrophobic groove of MEF2, which is used as a docking site by class IIa HDACs. However, NKL54 could also act as HDAC inhibitor (HDACI). Therefore, it is unclear which activity is predominant. Here, we show that NKL54 and similar derivatives are unable to release MEF2 from binding to class IIa HDACs. Comparative transcriptomic analysis classifies these molecules as HDACIs strongly related to SAHA/vorinostat. Low expressed genes are upregulated by HDACIs, while abundant genes are repressed. This transcriptional resetting correlates with a reorganization of H3K27 acetylation around the transcription start site (TSS). Among the upregulated genes there are several BH3-only family members, thus explaining the induction of apoptosis. Moreover, NKL54 triggers the upregulation of MEF2 and the downregulation of class IIa HDACs. NKL54 also increases the binding of MEF2D to promoters of genes that are upregulated after treatment. In summary, although NKL54 cannot outcompete MEF2 from binding to class IIa HDACs, it supports MEF2-dependent transcription through several actions, including potentiation of chromatin binding., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study evaluates white muscle growth and in vivo cell proliferation during a fasting and refeeding trial, using pejerrey (Odontesthes bonariensis) as animal model, in order to better understand the cellular basis governing catch-up growth. Experiments consisted of two groups of fish, a control group continuously fed ad libitum, and a group fasted for 2 weeks and then fed for another 2 weeks. We examined how the formation of new muscle fibers and their increase in size were related to muscle precursor cell (MPC) proliferation under both experimental conditions. During fasting, the number of 5-ethynyl-2'-deoxyuridine-positive (EdU+) cells decreased along with myogenic regulatory factor (MRF) mRNA levels related to myoblast proliferation and differentiation, and the muscle stem cell marker Pax7 mRNA level increased. Analysis of myomere cross-sectional area, distribution of muscle fiber sizes and number of fibers per myomere showed that muscle hypertrophy but not hyperplasia was inhibited during fasting. Both higher igf2 mRNA level and the persistence of cell proliferation could be supporting new myofiber formation. In contrast, an exacerbated MPC proliferation occurred during catch-up growth, and this increase in cell number could be contributing to the growth of both pre-existing and newly formed small fibers. The findings that some MPCs proliferate during fasting and that muscle growth mechanisms, hyperplasia and hypertrophy are differentially regulated could help to explain why re-fed fish could grow at faster rates, and why they return to the lost growth trajectory., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background: Complex Regional Pain Syndrome (CRPS) is a pathological persistence of spontaneous or evoked disproportionate pain. Several drugs are employed, but only bisphosphonates seem to have good outcomes. The purpose of our research is to analyze the characteristics of the cases victims of CRPS and study the beneficial effect of the intravenous nerindronic acid sodium salt (Nerixia®), in an attempt to improve the results in this disabling disease. Materials and methods: We retrospectively examined 30 cases of CRPS that had undergone intravenous nerindronic acid sodium salt therapy in our center. The patients were contacted after 12 months from the start of therapy and their clinical situation was assessed with Quick DASH Score. Results: The average age of our group was 59,76 years (span, 42-78), and female subjects were 84% (p-value <0.05). 72% of all cases were complications of wrist fractures.). The Quick DASH Score (19 points are the best result, 95 the worst outcome) average was 41,1 points. The values of Quick DASH Score differed significantly (p-value <0.001) according to the age of the patient. In addition, the DASH Score values were related to the sex of the patient (p-value <0.001). Male subjects have obtained a better score. After 12 months of intravenous therapy, 52% of cases reports that they still have joint stiffness. The DASH values differed significantly depending on the onset of intravenous treatment (p-value <0.001). Conclusion: Our study showed that the CRPS affects a population between 42 and 78 years, especially women. Treatment with intravenous bisphosphonates seems to lead to an improvement in CRPS symptoms, in particular administration between 3 and 6 months after the onset of the disease. In particular, women over 61 years of age seem to have a lower improvement in symptomatology after treatment. 52% of cases report that they still have joint stiffness.

Background: Fall from a height is one of the major causes of significant trauma with high morbidity and mortality rates. Traumatological damage control is often the primary treatment both for suicide attempt survivors and for accidental fall victims, but management of the hospitalization of psychiatric patients requires more resources than other patients., Methods: Retrospective multidisciplinary study (psychiatric and orthopaedic evaluation) and analysis of psychiatric and trauma characteristics of patients fallen from height admitted to our trauma centre. We analysed patterns of patients after suicidal jumps and accidental falls to look for possible trends that may trigger projects for further improvement of care., Results: 205 patients were analysed, 137 were included: 65 suicide attempt survivors and 72 accidental fall victims. Between these two groups there are no differences about the anaesthesiologic acute management or the number of damage control procedures. However, the psychiatric patients stay longer in hospital especially in intensive care unit with prolonged intubation (p<0.001). Suicide attempt survivors are significant correlated with fractures of feet, but the orthopaedic lesions do not involve an increase of definitive interventions (p< 0.05)., Conclusion: We showed that the suicide attempt survivors and accidental victims need the same acute management. The orthopedic definitive surgical procedures are similar between the two groups, but in spite of this patients with psychiatric disorder were associated with a statistically significant increase of care in intensive care unit and hospitalization. Our results allow to create a new multidisciplinary approach for these patients.

Unlabelled: Low-to-moderate levels of reactive oxygen species (ROS) govern different steps of neurogenesis via molecular pathways that have been decrypted only partially. Although it has been postulated that redox-sensitive molecules are involved in neuronal differentiation, the molecular bases for this process have not been elucidated yet. The aim of this work was therefore to study the role played by the redox-sensitive, multifunctional protein APE1/Ref-1 (APE1) in the differentiation process of human adipose tissue-derived multipotent adult stem cells (hAT-MASC) and embryonic carcinoma stem cells (EC) towards a neuronal phenotype., Methods and Results: Applying a definite protocol, hAT-MASC can adopt a neural fate. During this maturation process, differentiating cells significantly increase their intracellular Reactive Oxygen Species (ROS) levels and increase the APE1 nuclear fraction bound to chromatin. This latter event is paralleled by the increase of nuclear NF-κB, a transcription factor regulated by APE1 in a redox-dependent fashion. Importantly, the addition of the antioxidant N-acetyl cysteine (NAC) to the differentiation medium partially prevents the nuclear accumulation of APE1, increasing the neuronal differentiation of hAT-MASC. To investigate the involvement of APE1 in the differentiation process, we employed E3330, a specific inhibitor of the APE1 redox function. The addition of E3330, either to the neurogenic embryonic carcinoma cell line NT2-D1or to hAT-MASC, increases the differentiation of stem cells towards a neural phenotype, biasing the differentiation towards specific subtypes, such as dopaminergic cells. In conclusion, during the differentiation process of stem cells towards a neuroectodermic phenotype, APE1 is recruited, in a ROS-dependent manner, to the chromatin. This event is associated with an inhibitory effect of APE1 on neurogenesis that may be reversed by E3330. Therefore, E3330 may be employed both to boost neural differentiation and to bias the differentiation potential of stem cells towards specific neuronal subtypes. These findings provide a molecular basis for the redox-mediated hypothesis of neuronal differentiation program.