소화성 궤양의 Pathophysiology

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) and osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis and function is important. Mitophagy, a process that selectively clears damaged or dysfunctional mitochondria through autophagic machinery, functions to maintain mitochondrial quality control and homeostasis. IVDD and OA are similar joint diseases involving the degradation of cartilaginous tissues that are mainly caused by oxidative stress, cell apoptosis and extracellular matrix (ECM) degradation. Over the past decade, accumulating evidence indicates the essential role of mitophagy in the pathogenesis of IVDD and OA. Importantly, strategies by the regulation of mitophagy exert beneficial effects in the pre-clinical experiments. Given the importance and novelty of mitophagy, we provide an overview of mitophagy pathways and discuss the roles of mitophagy in IVDD and OA. We also highlight the potential of targeting mitophagy for the treatment of degenerative joint diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy and beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CDH6: cadherin 6; CEP: cartilaginous endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: extracellular matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin 1 beta; IMM: inner mitochondrial membranes; IVDD: intervertebral disc degeneration; MAPK8/JNK: mitogen-activated protein kinase 8; MFN1: mitofusin 1; MFN2: mitofusin 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: mitochondrial transmembrane potential; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; NFE2L2: nuclear factor: erythroid 2 like 2; NP: nucleus pulposus; OA: osteoarthritis; OPA1: OPA1: mitochondrial dynamin like GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin protein ligase; PD: Parkinson disease; PGAM5: PGAM family member 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator 1 alpha; PHF23: PHD finger protein 23; PINK1: PTEN induced putative kinase 1; ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin 1; SIRT2: sirtuin 2; SIRT3: sirtuin 3; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.

https://www.tandfonline.com/doi/pdf/10.1080/15548627.2020.1822097

Mitophagy in degenerative joint diseases

Discogenic back pain is multifactorial; hence, physicians often struggle to identify the underlying source of the pain. As a result, discogenic back pain is often hard to treat-even more so when clinical treatment strategies are of questionable efficacy. Based on a broad literature review, our aim was to define discogenic back pain into a series of more specific and interacting pathologies, and to highlight the need to develop novel approaches and treatment strategies for this challenging and unmet clinical need. Discogenic pain involves degenerative changes of the intervertebral disc, including structural defects that result in biomechanical instability and inflammation. These degenerative changes in intervertebral discs closely intersect with the peripheral and central nervous systems to cause nerve sensitization and ingrowth; eventually central sensitization results in a chronic pain condition. Existing imaging modalities are nonspecific to pain symptoms, whereas discography methods that are more specific have known comorbidities based on intervertebral disc puncture and injection. As a result, alternative noninvasive and specific diagnostic methods are needed to better diagnose and identify specific conditions and sources of pain that can be more directly treated. Currently, there are many treatments/interventions for discogenic back pain. Nevertheless, many surgical approaches for discogenic pain have limited efficacy, thus accentuating the need for the development of novel treatments. Regenerative therapies, such as biologics, cell-based therapy, intervertebral disc repair, and gene-based therapy, offer the most promise and have many advantages over current therapies. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment.

With an aging population, there is a proportional increase in the prevalence of intervertebral disc diseases. Intervertebral disc diseases are the leading cause of lower back pain and disability. With a high prevalence of asymptomatic intervertebral disc diseases, there is a need for accurate diagnosis, which is key to management. A thorough understanding of the pathophysiology and clinical manifestation aids in understanding the natural history of these conditions. Recent developments in radiological and biomarker investigations have potential to provide noninvasive alternatives to the gold standard, invasive discogram. There is a large volume of literature on the management of intervertebral disc diseases, which we categorized into five headings: (a) Relief of pain by conservative management, (b) restorative treatment by molecular therapy, (c) reconstructive treatment by percutaneous intervertebral disc techniques, (d) relieving compression and replacement surgery, and (e) rigid fusion surgery. This review article aims to provide an overview on various current diagnostic and treatment options and discuss the interplay between each arms of these scientific and treatment advancements, hence providing an outlook of their potential future developments and collaborations in the management of intervertebral disc diseases.

Intervertebral Disc Diseases PART 2: A Review of the Current Diagnostic and Treatment Strategies for Intervertebral Disc Disease

Innovations in the development of endoscopic spinal surgery were classified into different generations and reviewed. Future developments and directions for endoscopic spinal surgery were discussed. Surgical therapy for spinal disease has been gradually changing from traditional open surgery to minimally invasive spinal surgery. Recently, endoscopic spinal surgery, which initially was limited to the treatment of soft tissue lesions, has expanded to include other aspects of spinal disease and good clinical results have been reported. As the paradigm of spinal surgery shifts from open surgery to endoscopic surgery, we discussed the evolution of endoscopic spine surgery in our literature review. Through this description, we presented possibilities of future developments and directions in endoscopic spine surgery.

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Evolution of Spinal Endoscopic Surgery.

Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be associated with the pain pathway as a result of neurotization. Our goal is to perform a prospective study using radiofrequency ablation on sinuvertebral nerve and basivertebral nerve; evaluating its short and long term effect on pain score, disability score and patients’ outcome. A review in literature is done on the pathoanatomy, pathophysiology and pain generation pathway in degenerative disc disease and chronic back pain. 30 patients with 38 levels of intervertebral disc presented with discogenic back pain with bulging degenerative intervertebral disc or spinal stenosis underwent Uniportal Full Endoscopic Radiofrequency Ablation application through either Transforaminal or Interlaminar Endoscopic Approaches. Their preoperative characteristics are recorded and prospective data was collected for Visualized Analogue Scale, Oswestry Disability Index and MacNab Criteria for pain were evaluated. There was statistically significant Visual Analogue Scale improvement from preoperative state at post-operative 1wk, 6 months and final follow up were 4.4 ± 1.0, 5.5 ± 1.2 and 5.7 ± 1.3, respectively, p < 0.0001. Oswestery Disability Index improvement from preoperative state at 1week, 6 months and final follow up were 45.8 ± 8.7, 50.4 ± 8.2 and 52.7 ± 10.3, p < 0.0001. MacNab criteria showed excellent outcomes in 17 cases, good outcomes in 11 cases and fair outcomes in 2 cases Sinuvertebral Nerve and Basivertebral Nerve Radiofrequency Ablation is effective in improving the patients’ pain, disability status and patient outcome in our study.

Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature.

Early Outcomes of Endoscopic Contralateral Foraminal and Lateral Recess Decompression via an Interlaminar Approach in Patients with Unilateral Radiculopathy from Unilateral Foraminal Stenosis.

Incidental Durotomy During Endoscopic Stenosis Lumbar Decompression: Incidence, Classification, and Proposed Management Strategies

In the first phase of development of lumbar endoscopic spine surgery, the focus was on removal of soft disc material through the working corridor of Kambin's triangle using transforaminal endoscopic lumbar discectomy. With the introduction of the interlaminar approach and increased interest from both industry and surgeons, there has been an exponential development of endoscopic surgical equipment and a corresponding expansion of endoscopic techniques. Endoscopic treatment strategies are applied to conditions ranging from contained prolapsed intervertebral discs to noncontained migrated herniated discs, hard calcified discs, spinal stenosis in the central or lateral recess and the foraminal and extraforaminal region, and other combinations of degenerative conditions requiring decompression or fusion surgery. The further expansion of endoscopic surgical management involving complicated spinal cases and the final quartet of trauma, infections, tumors, and possibly deformities could be the future stage of endoscopic spine surgery development. This article covers the full range of current treatment strategies and presents possible future developments of endoscopic spine surgery for the management of lumbar spinal conditions.

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Il-Tae Jang

Papers

Intervertebral Disc Diseases PART 2: A Review of the Current Diagnostic and Treatment Strategies for Intervertebral Disc Disease

Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature.

Early Outcomes of Endoscopic Contralateral Foraminal and Lateral Recess Decompression via an Interlaminar Approach in Patients with Unilateral Radiculopathy from Unilateral Foraminal Stenosis.

Incidental Durotomy During Endoscopic Stenosis Lumbar Decompression: Incidence, Classification, and Proposed Management Strategies

A Narrative Review of Development of Full-Endoscopic Lumbar Spine Surgery.