Scientific reports
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Meta Analysis
Impact of timing of surgery in elderly hip fracture patients: a systematic review and meta-analysis.
We aimed to assess the impact of timing of surgery in elderly patients with acute hip fracture on morbidity and mortality. We systematically searched MEDLINE, the Cochrane Library, Embase, PubMed, and trial registries from 01/1997 to 05/2017, as well as reference lists of relevant reviews, archives of orthopaedic conferences, and contacted experts. Eligible studies had to be randomised controlled trials (RCTs) or prospective cohort studies, including patients 60 years or older with acute hip fracture. ⋯ No statistical significant different mortality risk was observed when comparing patients operated on within or after 24 hours (RR 0.82, 95% CI 0.67-1.01). Adjusted data demonstrated fewer complications (8% vs. 17%) in patients who had early surgery, and increasing risk for pressure ulcers with increased time of delay in another study. Early hip surgery within 48 hours was associated with lower mortality risk and fewer perioperative complications.
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Pediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. ⋯ Differences in sensitivity may be due in part to nectin-1 expression, which predicted responses to the viruses. Treatment with oHSV resulted in prolonged survival in both pediatric and adult intracranial patient-dervied tumor xenograft models. Our results suggest that pediatric brain tumors are ideal targets for oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to predict patient response to oHSV.
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Osteoarthritis (OA) is a major degenerative joint condition that causes articular cartilage destruction. It was recently found that enhancement of chondroclasts and suppression in Treg cell differentiation are involved in the pathogenesis of OA. Kartogenin (KGN) is a small drug-like molecule that induces chondrogenesis in mesenchymal stem cells (MSCs). ⋯ Decreased chondroclast expression, and increased Treg cell expression. KGN revealed therapeutic activity with the potential to reduce pain and improve cartilage destruction. Thus, KGN could be a therapeutic molecule for OA that inhibits cartilage damage.
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The amygdala is an important component of the limbic system that participates in the control of the pain response and modulates the affective-motivational aspect of pain. Neuropathic pain is a serious public health problem and has a strong affective-motivational component that makes it difficult to treat. The central (CeA), basolateral (BLA) and lateral (LA) nuclei of the amygdala are involved in the processing and regulation of chronic pain. ⋯ The results showed that the anterior and posterior portions of the BLA and the central portion of the CeA are involved in controlling neuropathic pain. The inactivation of these nuclei reversed hyperalgesia, allodynia and depressive-like behavior in animals with peripheral neuropathy. Taken together, our findings improve our understanding of the neurocircuitry involved in persistent pain and the roles of specific amygdala subnuclei in the modulation of neuropathic pain, including the neurocircuitry that processes the affective-motivational component of pain.
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Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. ⋯ Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis.