No abstract

Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (dney in protein), an upstream regulator of the Hippo signaling pathway encoded by the gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in and MCF10A cells. We recently identified YAP as an essential component of the glomerular filtration barrier that promotes podocyte survival by inhibiting dendrin pro-apoptotic function. Despite these recent advances, the signaling pathways that mediate podocyte injury remain poorly understood. Here we tested the hypothesis that, similar to its role in other model systems, KIBRA promotes podocyte injury. We found increased expression of KIBRA and phosphorylated YAP protein in glomeruli of patients with biopsy-proven focal segmental glomerulosclerosis (FSGS). KIBRA/ overexpression in murine podocytes promoted LATS kinase phosphorylation, leading to subsequent YAP Ser-127 phosphorylation, YAP cytoplasmic sequestration, and reduction in YAP target gene expression. Functionally, KIBRA overexpression induced significant morphological changes in podocytes, including disruption of the actin cytoskeletal architecture and reduction of focal adhesion size and number, all of which were rescued by subsequent YAP overexpression. Conversely, constitutive KIBRA knockout mice displayed reduced phosphorylated YAP and increased YAP expression at baseline. These mice were protected from acute podocyte foot process effacement following protamine sulfate perfusion. KIBRA knockdown podocytes were also protected against protamine-induced injury. These findings suggest an important role for KIBRA in the pathogenesis of podocyte injury and the progression of proteinuric kidney disease.

MI, minimally invasive.

Symptoms from synovial cysts are produced by neural compression in the spinal canal or the foramen. Few cases of extraforaminal synovial cyst have been published in the literature. This is a case report of a 65-year-old female who presented with a three-month history of sciatic pain and no relief with conservative treatment. MRI showed a left-sided extraforaminal synovial cyst at L5-S1 with compression of the L5 nerve root at the lateral portion of the foramen. Minimally invasive surgery for resection was performed using an extraforaminal tubular microscopic endoscopy-assisted approach. The patient improved clinically and remained symptom-free for the entire follow-up of 30 months.

Introduction Unrepaired annular defects potentially increase the reherniation rate after lumbar discectomies and have been shown to accelerate degenerative changes after discographies. This is the first study to test an injectable biological substance to repair annular defects in vivo. We used high-density collagen gel in a needle-punctured rat-tail model. Needle puncturing leads to extrusion of NP tissue with subsequent degenerative changes (4). Restoring annular integrity will help retain the NP material and therefore inhibit these changes. Materials and Methods We punctured the S3/S4 intervertebral disc (IVD) of 30 athymic rats using an 18-gauge needle. Subsequently high-density collagen (HDC) gel was injected to seal the defect. Riboflavin (RF) was added to increase the stiffness of the collagen gel by inducing chemical cross-link formation. Animals were subdivided into four groups. The first group was injected with uncross-linked HDC gel (n = 6), the second with cross-linked collagen using 0.5 mM (n = 8) and the third 0.75 mM (n = 8) concentration of RF. The fourth group (n = 8) served as control and was left untreated after needle puncture. The animals were followed up at weeks 1, 2, 5, 12, and 18 with X-ray measurements to assess the disc heights and MR imaging to evaluate degenerative changes according to a modified Pffirmann grading system. We developed an algorithm based on T2-relaxation time measurements to assess the size of the nucleus by the number of NP voxels that compose it (Fig. 1). Animals were sacrificed at 1, 2, 5 (n = 10), and 18 weeks (n = 20). Histological analysis of the collected tails was performed to study the fate of the collagen using Safranin O and fluorescent stains: FITC for collagen and DAPI for host cells. Disc degeneration was assessed histologically according to the established Han grading system and NP size according to cross-sectional area measurements. Half of the tails from the 18-week time point underwent mechanical testing. We performed stress relaxation tests to measure the stiffness of the discs and their ability to pressurize. Damping quality was measured using frequency sweep tests. Explanted segments were exposed to sinusoidal strains at variable frequencies ranging from 0.01 to 0.3 Hz at amplitudes of ± 10% strain. Results Disc Degeneration Over 18 weeks RF cross-linked groups retained significantly more NP tissue in the disc space than the uncross-linked and the control groups according to NP voxel count and histological NP cross-section measurements (p < 0.05) (Fig. 1). There was no significant difference in NP size between 0.5 and 0.75 mM groups (p > 0.05). Both groups retained approximately 70% of NP size when compared with healthy discs and maintained a disc height of over 80% compared with the prepuncture state. Both cross-linked groups showed no significant histological degenerative changes (Fig. 1). The NP showed regular cellularity and matrix morphology. The AF maintained its organization and lamellar structure. Both groups showed similar damping qual...

Introduction The gold standard treatment for degenerative lumbar listhesis is decompression with fusion. According to a SPORT trail, 35% of patients with this condition present with additional symptomatic stenosis most commonly on the adjacent segment. However, the most appropriate surgical technique to treat the stenosis adjacent to the instrumented segment remains controversial. Extended fusion with open decompression could lead to adjacent segment disease; simple decompression without fusion might lead to clinically relevant instability at the index level. To date, there is no study evaluating the biomechanical impact of decompression procedures in this clinical scenario. The presented work is the first to analyze the mechanical effect of minimally invasive (MI) and open decompression procedures adjacent to instrumented segments in the lumbar spine. Material and Methods Tested conditions: Seven cadaveric lumbar spines were tested. The entire lumbar spine was assessed intact (baseline) and for the following conditions: (1) Instrumented fusion at L4/L5. (2) MI decompression through a tubular retractor at L3/L4 with a unilateral approach for bilateral internal decompression and complete removal of the flavum ligament. (3) Additional bilateral partial facetectomy at L3/L4 (20% of the facet joints). (4) Laminectomy at L3/L4. Mechanical testing: Specimens were carefully cleaned of muscular tissue and potted at T12 and S2–S4. Nonconstraining, nondestructive pure moment (torque) loading (7.5 Nm) was applied to each specimen through a system of cables and pulleys in conjunction with a standard servohydraulic test system. Loads were applied in 1.25 Nm increments until the maximum load was reached. Each condition was tested for flexion extension, lateral bending, left and right axial rotation, and compression. The range of motion (ROM) of each segment was assessed stereophotogrammetrically by capturing the three-dimensional displacement of infrared-emitting markers which were rigidly attached to each vertebra from L1–S1. ROM was measured in degrees and used to quantify spinal stability. One-way repeated measures analysis of variance (ANOVA) followed by the Fisher least significant difference test were used to compare ROM. Results All data are shown as normalized ratio. Compared with intact L3/L4 after L4/L5 fusion, MIS decompression significantly increased the L3/L4 ROM by 13% ( p = 0.034) for flexion extension (20% more than baseline) and 23% for axial rotation ( p = 0.003) (26% more than baseline). Partial facetectomy further increased the ROM by 15% for axial rotation ( p = 0.032) (46% more than baseline) but not for flexion extension. Laminectomy further increased the ROM for flexion extension by 12% ( p = 0.05) (38% more than baseline) and for axial rotation by 17% ( p = 0.023) (58% more than baseline). There were no significant changes for lateral bending or compression tests for any tested condition. Looking at the overall motion of the lumbar spine, L4/L5 fusion decreased flexion extension by 20% (< 0.001) and axial rotation by 19% ( p < 0.001). With each decompressive procedure, the overall motion returned to almost normal in a stepwise manner reaching 95% of baseline after laminectomy. Conclusion Mechanical alterations of MI decompression adjacent to fused segments are comparable to mechanical alterations of these procedures without adjacent fusion shown in other studies. Therefore, adjacent fusion does not significantly increase instability of MI decompression. The preservation of the facet joints is crucial for segmental stability. Laminectomy adjacent to fused segment causes an up to 58% increase in segmental ROM and is therefore not recommended in the presented clinical scenario.