Nebulized Ketamine Used for Pain Management of Orthopedic Trauma

BackgroundKetamine is a noncompetitive N-methyl-D-aspartate/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization and hyperalgesia. When administered via i.v. (push-dose, short infusion, or continuous infusion) or intranasal routes, ketamine has shown to be effective in patients with acute traumatic pain. However, when i.v. access is not attainable or readily available, the inhalation route of ketamine administration via breath-actuated nebulizer (BAN) provides a noninvasive and titratable method of analgesic delivery. The use of nebulized ketamine has been studied in areas of postoperative management of sore throat and acute traumatic musculoskeletal and abdominal pain. To our knowledge, this is the first case series describing the use of nebulized ketamine for analgesia and orthopedic reduction.Case SeriesWe describe 4 patients who presented to the emergency department with acute traumatic painful conditions (one patellar dislocation, one shoulder dislocation, and two forearm fractures) and received nebulized ketamine for management of their pain.Why Should an Emergency Physician Be Aware of This?Administration of nebulized ketamine via BAN can be used as analgesic control for musculoskeletal trauma, as it can be administrated to patients with difficult i.v. access, has a rapid onset of analgesic effects with minimal side effects, and remains opioid-sparing.     

Selective Laser Melting of Al-Based Matrix Composites with Al2O3 Reinforcement: Features and Advantages

Aluminum matrix composites (AMC) are of great interest and importance as high-performance materials with enhanced mechanical properties. Al₂O₃ is a commonly used reinforcement in AMCs fabricated by means of various technological methods, including casting and sintering. Selective laser melting (SLM) is a suitable modern method of the fabrication of net-shape fully dense parts from AMC with alumina. The main results, achievements, and difficulties of SLM applied to AMCs with alumina are discussed in this review and compared with conventional methods. It was shown that the initial powder preparation, namely the particle size distribution, sphericity, and thorough mixing, affected the final microstructure and properties of SLMed materials drastically. The distribution of reinforcing particles tends to consolidate the near-melting pool-edges process because of pushing by the liquid–solid interface during the solidification process that is a common problem of various fabrication methods. The achievement of an homogeneous distribution was shown to be possible through both the thorough mixing of the initial powders and the precise optimization of SLM parameters. The strength of the AMCs fabricated by the SLM method was relatively low compared with materials produced by conventional methods, while for superior relative densities of more than 99%, hardness and tribological properties were obtained, making SLM a promising method for the Al-based matrix composites with Al₂O₃.     

Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m² for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was −20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (−12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.     

Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis

Liver kinase B1 (LKB1) is a ubiquitously expressed kinase involved in the regulation of cell metabolism, growth, and inflammatory activation. We previously reported that a single nucleotide polymorphism in the gene encoding LKB1 is a risk factor for multiple sclerosis (MS). Since astrocyte activation and metabolic function have important roles in regulating neuroinflammation and neuropathology, we examined the serine/threonine kinase LKB1 in astrocytes in a chronic experimental autoimmune encephalomyelitis mouse model of MS. To reduce LKB1, a heterozygous astrocyte-selective conditional knockout (het-cKO) model was used. While disease incidence was similar, disease severity was worsened in het-cKO mice. RNAseq analysis identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in het-cKO mice relating to mitochondrial function, confirmed by alterations in mitochondrial complex proteins and reductions in mRNAs related to astrocyte metabolism. Enriched pathways included major histocompatibility class II genes, confirmed by increases in MHCII protein in spinal cord and cerebellum of het-cKO mice. We observed increased numbers of CD4+ Th17 cells and increased neuronal damage in spinal cords of het-cKO mice, associated with reduced expression of choline acetyltransferase, accumulation of immunoglobulin-γ, and reduced expression of factors involved in motor neuron survival. In vitro, LKB1-deficient astrocytes showed reduced metabolic function and increased inflammatory activation. These data suggest that metabolic dysfunction in astrocytes, in this case due to LKB1 deficiency, can exacerbate demyelinating disease by loss of metabolic support and increase in the inflammatory environment.     

miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD)

MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation resistance.     

Optimization of endovenous laser coagulation: in vivo experiments

Lasers in Medical Science - Finding optimal parameters of endovenous laser coagulation using the radiation with a wavelength of 1910 nm. In vivo experiments have been carried out on the...