Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.
Animals ; Brain-Derived Neurotrophic Factor/*genetics ; *Cord Blood Stem Cell Transplantation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Profiling ; *Gene Expression Regulation ; Humans ; Locomotion ; Nerve Growth Factor/genetics ; Rats ; Spinal Cord Injuries/*therapy

BACKGROUND: The Kirschner wire (K-wire) technique allows stable fixation of bone fragments without periosteal dissection, which often lead to bone segment scattering and loss. The authors used the K-wire fixation to simplify the treatment of laborious comminuted zygomatic bone fracture and report outcomes following the operation. METHODS: A single-institution retrospective review was performed for all patients with comminuted zygomatic bone fractures between January 2010 and December 2013. In each patient, the zygoma was reduced and fixed with K-wire, which was drilled from the cheek bone and into the contralateral nasal cavity. For severely displaced fractures, the zygomaticofrontal suture was first fixated with a microplate and the K-wire was used to increase the stability of fixation. Each wire was removed approximately 4 weeks after surgery. Surgical outcomes were evaluated for malar eminence, cheek symmetry, Kwire site scar, and complications (based on a 4-point scale from 0 to 3, where 0 point is 'poor' and 3 points is 'excellent'). RESULTS: The review identified 25 patients meeting inclusion criteria (21 men and 4 women). The mean age was 52 years (range, 15-73 years). The mean follow up duration was 6.2 months. The mean operation time was 21 minutes for K-wire alone (n=7) and 52 minutes for K-wire and plate fixation (n=18). Patients who had received K-wire only fixation had severe underlying diseases or accompanying injuries. The mean postoperative evaluation scores were 2.8 for malar contour and 2.7 for K-wire site scars. The mean patient satisfaction was 2.7. There was one case of inflammation due to the K-wire. CONCLUSION: The use of K-wire technique was associated with high patient satisfaction in our review. K-wire fixation technique is useful in patient who require reduction of zygomatic bone fractures in a short operating time.
Bone Wires ; Cheek ; Cicatrix ; Follow-Up Studies ; Fractures, Bone ; Humans ; Inflammation ; Male ; Nasal Cavity ; Patient Satisfaction ; Retrospective Studies ; Sutures ; Zygoma ; Zygomatic Fractures*

The use of human umbilical cord blood-derived mesenchymal stem cells for cell transplantation therapy holds great promise for repairing spinal cord injury. Here we report the first clinical trial transplantation of human umbilical cord (hUCB)-derived mesenchymal stem cells (MSCs) into the spinal cord of a dog suspected to have fibrocartilaginous embolic myelopathy (FCEM) and that experienced a loss of deep pain sensation. Locomotor functions improved following transplantation in a dog. Based on our findings, we suggest that transplantation of hUCB-derived MSCs will have beneficial therapeutic effects on FCEM patients lacking deep pain sensation.
Animals ; Cartilage Diseases/etiology/therapy/*veterinary ; *Cord Blood Stem Cell Transplantation/veterinary ; Dog Diseases/etiology/*therapy ; Dogs ; Embolism/etiology/therapy/*veterinary ; Female ; Humans ; Mesenchymal Stromal Cells/cytology/*metabolism ; Spinal Cord Diseases/etiology/therapy/*veterinary ; Treatment Outcome

Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 microL (n = 18), 50 microL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 microL was used, but not after 50 microL was applied. In the 50 microL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo.
Animals ; Balloon Embolectomy/*methods ; Disease Models, Animal ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Compression/*therapy

We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm2 section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals.
Abdominal Wall/*surgery ; Animals ; Biocompatible Materials/*therapeutic use ; Dogs ; Female ; Intestinal Mucosa/cytology/transplantation ; Intestine, Small/cytology/*transplantation ; Polypropylenes/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tensile Strength ; Tissue Adhesions ; *Tissue Scaffolds ; Transplantation, Heterologous/*methods ; *Wound Healing

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in vascular functions, including vasorelaxation. We here investigated the pharmacological effect of the natural product syringaresinol on vascular relaxation and eNOS-mediated NO production as well as its underlying biochemical mechanism in endothelial cells. Treatment of aortic rings from wild type, but not eNOS-/- mice, with syringaresinol induced endothelium-dependent relaxation, which was abolished by addition of the NOS inhibitor NG-monomethyl-L-arginine. Treatment of human endothelial cells and mouse aortic rings with syringaresinol increased NO production, which was correlated with eNOS phosphorylation via the activation of Akt and AMP kinase (AMPK) as well as elevation of intracellular Ca2+ levels. A phospholipase C (PLC) inhibitor blocked the increases in intracellular Ca2+ levels, AMPK-dependent eNOS phosphorylation, and NO production, but not Akt activation, in syringaresinol-treated endothelial cells. Syringaresinol-induced AMPK activation was inhibited by co-treatment with PLC inhibitor, Ca2+ chelator, calmodulin antagonist, and CaMKKbeta siRNA. This compound also increased eNOS dimerization, which was inhibited by a PLC inhibitor and a Ca2+-chelator. The chemicals that inhibit eNOS phosphorylation and dimerization attenuated vasorelaxation and cGMP production. These results suggest that syringaresinol induces vasorelaxation by enhancing NO production in endothelial cells via two distinct mechanisms, phosphatidylinositol 3-kinase/Akt- and PLC/Ca2+/CaMKKbeta-dependent eNOS phosphorylation and Ca2+-dependent eNOS dimerization.
Animals ; Aorta/*drug effects/physiology ; Enzyme Activation/drug effects ; Furans/*pharmacology ; Gene Deletion ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Lignans/*pharmacology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide Phospholipase C/metabolism ; Phosphorylation/drug effects ; Protein Multimerization/*drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Vasodilation/*drug effects

The use of graft materials in bladder mucosa has been examined in animal models, but debate exists over which materials are effective. Intestine has been used as a substitute in augmentation cystoplasty for patients with neuropathic bladder, but serious adverse effects of the operation have occurred in some instances. We report a case of a successful repair of an enterovesical fistula by use of bovine pericardium. The patient has remained well for 2.5 years. We suggest that bovine pericardium may be a suitable option as a bladder substitute.
Fistula ; Humans ; Intestines ; Models, Animal ; Mucous Membrane ; Pericardium ; Radiation Injuries ; Transplants ; Urinary Bladder ; Urinary Bladder Fistula ; Urinary Bladder, Neurogenic

Most foreign bodies in the lower genitourinary tract are self-inserted via the urethra as the result of exotic impulses, psychometric problems, sexual curiosity, or sexual practice while intoxicated. Diagnosis of these foreign bodies can be done by clinical history, physical examination, and image studies of the patient. The treatment of foreign bodies is determined by their size, location, shape, and mobility. In most cases, minimally invasive procedures such as endoscopic removal are recommended to prevent bladder and urethral injuries. In some cases, however, surgical treatment should be done if the foreign bodies cannot be removed by the endoscopic procedure or further injuries are expected as a result of the endoscopic procedures. Herein we present 2 cases of self-inserted lower genitourinary foreign bodies with a brief review of the literature.
Exploratory Behavior ; Foreign Bodies ; Humans ; Physical Examination ; Psychometrics ; Urethra ; Urinary Bladder

Systemic lupus erythematosus (SLE) is a typical autoimmune disease that's characterized by various autoantibodies to nuclear and cytoplasmic antigens. The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of SLE. However, a small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative ANA tests. Our report describes a 16-yr-old female who presented with the clinical manifestations of SLE such as malar rash, photosensitivity, arthritis, lymphopenia, pericarditis and proteinuria. The serum autoantibodies were all negative and renal biopsy showed that the histopathological changes of immune complex mediated the focal segmental necrotizing glomerulonephritis with crescent formation. She was treated with monthly pulse cyclophosphamide along with corticosteroids. During the 2-yr follow-up period, the proteinuria was markedly decreased and all of the ANA and anti-double stranded DNA antibody tests were negative. This case suggests that ANA may not be required in the pathogenesis of lupus nephritis.
Adolescent ; Antibodies, Antinuclear/*immunology ; Biopsy ; Female ; Follow-Up Studies ; Humans ; Lupus Nephritis/diagnosis/*immunology ; Tomography, X-Ray Computed