scholarly journals Influence of endplate avulsion and Modic changes on the inflammation profile of herniated discs: a proteomic and bioinformatic approach

Author(s):  
Niek Djuric ◽  
Shanmuganathan Rajasekaran ◽  
Chitra Tangavel ◽  
Muthurajan Raveendran ◽  
Dilip Chand Raja Soundararajan ◽  
...  
2019 ◽  
Vol 30 (6) ◽  
pp. 767-771
Author(s):  
Xinqiang Yao ◽  
Ruoting Ding ◽  
Junhao Liu ◽  
Siyuan Zhu ◽  
Jingshen Zhuang ◽  
...  

OBJECTIVEThe aim of this study was to evaluate the effect of lumbar sacralization on the level of vertebral slip and disc degeneration in patients with L4 spondylolysis.METHODSThe authors analyzed data from 102 cases in which patients underwent surgical treatment for L4 spondylolysis and spondylolisthesis at their institution between March 2007 and September 2016. Lumbar sacralization was characterized by the presence of pseudarthrosis and/or bony fusion between the L5 transverse process and sacrum, and the type of lumbosacral transitional vertebra (LSTV) was evaluated with the Castellvi classification. The amount of vertebral slippage was measured using the Taillard technique and Meyerding grade. Degeneration of the L4–5 segment was quantified using the Pfirrmann and Modic classifications. Patients were divided into 2 groups based on the presence or absence of sacralization, and the amount of vertebral slip and degeneration of the L4–5 segment was compared between groups.RESULTSLumbar sacralization was present in 37 (36%) of 102 patients with L4 spondylolysis. The LSTV was type IIa in 10 cases, type IIb in 7, type IIIa in 2, and type IIIb in 18. The levels of vertebral slip and disc degeneration in the group of patients with sacralization were significantly greater than in the group without sacralization. No significant difference was found between the 2 groups with respect to Modic changes.CONCLUSIONSThe increased stability between a sacralized L5 and the sacrum may predispose the L4–5 segment to greater instability and disc degeneration in patients with L4 spondylolysis.


2020 ◽  
Vol 15 ◽  
Author(s):  
Zakia Akter ◽  
Anamul Haque ◽  
Md. Sabir Hossain ◽  
Firoz Ahmed ◽  
Md Asiful Islam

Background: Cholera, a diarrheal illness causes millions of deaths worldwide due to large outbreaks. Monoclonal antibody used as therapeutic purposes of cholera are prone to be unstable due to various factors including self-aggregation. Objectives: In this bioinformatic analysis, we identified the aggregation prone regions (APRs) of different immunogens of antibody sequences (i.e., CTB, ZnM-CTB, ZnP-CTB, TcpA-CT-CTB, ZnM-TcpA-CT-CTB, ZnP-TcpA-CT-CTB, ZnM-TcpA, ZnP-TcpA, TcpA-CT-TcpA, ZnM-TcpA-CT-TcpA, ZnP-TcpA-CT-TcpA, Ogawa, Inaba and ZnM-Inaba) raised against Vibrio cholerae. Methods: To determine APRs in antibody sequences that were generated after immunizing Vibrio cholerae immunogens on Mus musculus, a total of 94 sequences were downloaded as FASTA format from a protein database and the algorithms such as Tango, Waltz, PASTA 2.0, and AGGRESCAN were followed to analyze probable APRs in all of the sequences. Results: A remarkably high number of regions in the monoclonal antibodies were identified to be APRs which could explain a cause of instability/short term protection of anticholera vaccine. Conclusion: To increase the stability, it would be interesting to eliminate the APR residues from the therapeutic antibodies in a such way that the antigen binding sites or the complementarity determining region loops involved in antigen recognition are not disrupted.


2021 ◽  
pp. 219256822097608
Author(s):  
Dinesh Kumarasamy ◽  
Shanmuganathan Rajasekaran ◽  
Sri Vijay Anand K. S ◽  
Dilip Chand Raja Soundararajan ◽  
Ajoy Prasad Shetty T ◽  
...  

Study design: Prospective comparative cohort study. Objectives: The study aims to elucidate the relationship between Modic endplate changes and clinical outcomes after a lumbar microdiscectomy. Methods: Consecutive patients undergoing microdiscectomy for lumbar disc herniation (LDH) were prospectively studied. Pre-operative clinical and radiological parameters were recorded. The pain was assessed by Numeric pain rating scale (NPRS), and functional assessment by Oswestry Disability Index (ODI). Minimal clinically important difference (MCID) in outcome was calculated for both the groups. Complications related to surgery were studied. Follow-up was done at 6 weeks, 3 months, 6 months and 1 year. Mac Nab criteria were used to assess patient satisfaction at 1 year. Results: Out of 309 patients, 86 had Modic changes, and 223 had no Modic changes. Both groups had similar back pain (p-value: 0.07) and functional scores (p-value: 0.85) pre-operatively. Postoperatively patients with Modic changes had poorer back pain and ODI scores in the third month, sixth month and 1 year (p-value: 0.001). However, MCID between the groups were not significant (p-value: 0.18 for back pain and 0.58 for ODI scores). Mac Nab criteria at 1 year were worse in Modic patients (p-value: 0.001). No difference was noted among Modic types in the pre-operative and postoperative pain and functional outcomes. Four patients in Modic group (4.7%) and one patient in the non-Modic group (0.5%) developed postoperative discitis (p-value: 0.009). Conclusions: Preoperative Modic changes in lumbar disc herniation is associated with less favorable back pain, functional scores and patient satisfaction in patients undergoing microdiscectomy.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
B Kewlani ◽  
I Hussain ◽  
J Greenfield

Abstract The hallmark symptom of spontaneous intracranial hypotension (SIH) is orthostatic headaches which manifests secondary to cerebrospinal fluid (CSF) hypovolaemia. Well-recognised aetiologies include trauma which includes procedures such as lumbar punctures and spinal surgery. More recently, structural defects such as bony osteophytes and calcified or herniated discs have been attributed to mechanically compromising dural integrity consequently resulting in CSF leak and symptom manifestation. A thorough literature review noted only a handful of such cases. We report the case of a thirty-two-year-old Asian female who presented with a one-month history of new-onset progressively worsening orthostatic headaches. Workup included MRI of the thoracic spine which revealed an epidural collection of CSF consequently prompting a dynamic CT-myelogram of the spine which not only helped to confirm severe cerebral hypotension but also suggested the underlying cause as being a dorsally projecting osteophyte-complex at level T2-3. Conservative and medical management including bed rest, analgesia, mechanical compression, and epidural blood patches failed to alleviate symptoms and a permanent surgical cure was eventually sought. The surgery involved T2-T3 laminectomy and osteophytectomy and at a 3-month follow-up, complete resolution of symptoms was noted.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew R. Swiatnicki ◽  
Eran R. Andrechek

AbstractThe E2F family of transcription factors is important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis and metastasis. Alteration of the Rb/E2F pathway occurs in various forms of cancer, including breast cancer. E2F1 ablation has been shown to decrease metastasis in MMTV-Neu and MMTV-PyMT transgenic mouse models of breast cancer. Here we take a bioinformatic approach to determine the E2F1 regulated genomic alterations involved in the metastatic cascade, in both Neu and PyMT models. Through gene expression analysis, we reveal few transcriptome changes in non-metastatic E2F1−/− tumors relative to transgenic tumor controls. However investigation of these models through whole genome sequencing found numerous differences between the models, including differences in the proposed tumor etiology between E2F1−/− and E2F1+/+ tumors induced by Neu or PyMT. For example, loss of E2F1 within the Neu model led to an increased contribution of the inefficient double stranded break repair signature to the proposed etiology of the tumors. While the SNV mutation burden was higher in PyMT mouse tumors than Neu mouse tumors, there was no statistically significant differences between E2F WT and E2F1 KO mice. Investigating mutated genes through gene set analysis also found a significant number of genes mutated in the cell adhesion pathway in E2F1−/− tumors, indicating this may be a route for disruption of metastasis in E2F1−/− tumors. Overall, these findings illustrate the complicated nature of uncovering drivers of the metastatic process.


Author(s):  
Terence W. Friedlander ◽  
Colin C. Pritchard ◽  
Himisha Beltran

Although biopsies of metastatic prostate cancer are rarely undertaken in the clinical setting, there is increasing interest in developing personalized approaches to therapy by taking into account the genetic and phenotypic changes in an individual tumor. Indeed, analysis of metastatic prostate tumors can predict sensitivity to agents that inhibit DNA repair and resistance to novel hormonal agents, such as abiraterone and enzalutamide, and identify phenotypic changes, such as neuroendocrine differentiation, that have important clinical implications. Although obtaining metastatic tumor tissue is necessary for this genomic and molecular profiling, knowing when to biopsy, selecting the appropriate metastatic lesion, and interpreting the results are major challenges facing clinicians today. In this article, we discuss the rationale for obtaining metastatic tumor tissue, review the bioinformatic approach to analyzing these specimens, discuss the timing and approach to solid and liquid tumor biopsies, review the challenges associated with obtaining and acting on clinically relevant results, and discuss opportunities for the future.


2017 ◽  
Vol 68 (4) ◽  
pp. 419-424 ◽  
Author(s):  
Mark Georgy ◽  
Mark Stern ◽  
Kieran Murphy

This review presents a summary of the pathology and epidemiology of Modic changes and the possible role of Propionibacterium acnes. This information is followed by a synthesis of the most recent clinical research involved in culturing the discs of patients with degenerative disc disease for the presence of bacteria. We also discuss a randomized controlled trial that investigates the effects of antibiotics on patients with chronic low back pain and type 1 Modic changes. We conclude with a brief discussion of the difficulties involved in this research and the significance of the findings.


2012 ◽  
Vol 21 (11) ◽  
pp. 2271-2279 ◽  
Author(s):  
Rikke K. Jensen ◽  
Charlotte Leboeuf-Yde ◽  
Niels Wedderkopp ◽  
Joan S. Sorensen ◽  
Tue S. Jensen ◽  
...  

2021 ◽  
pp. 48
Author(s):  
Majd Alrayes

Introduction: Intervertebral disc prolapse is a very common abnormality found in the population, that can manifest in a variety of complaints like back pain, radiculopathy, and even to the extent that it might lead to more adverse neurological deficits. Symptoms improve in majority of patients only with conservative treatment. However, some patients may require surgical intervention. In some cases, spontaneous regression of herniated disc can be seen. Thus, the interest in the phenomenon of spontaneous resorption of the herniated discs has increased, which raised the controversy regarding managing such patients. Here, we report a case of a huge lumbosacral spontaneous disc resolution at the level of L5-S1 in which clinical improvement was associated with a significant decrease in the size of a huge, herniated disc. In addition, we performed a comprehensive review of literature of all reported cases of spontaneous disc resolution to provide an updated discussion of such an underlooked phenomena. Case Report: A 53-year-old female not known to have any medical illness presented at the Neurosurgery Clinic with complaints of chronic back pain for six years which was progressing and radiating to both of her lower extremities (right more than left) and had become more intense in the last year. It was slightly relieved by simple analgesics and aggravated by sitting or lying down. There was no history of trauma, weaknesses, or sphincteric disturbances. Upon evaluation in our clinic, local exam revealed lower back midline tenderness at the level of L5-S1 vertebrae. No tenderness was observed in the paravertebral area or facets. Straight leg raising test was positive at 70º in the right side and 90º in the left, normal power, intact sensation, normal tone, and reflexes. Negative Babinski and clonus was noted in both limbs. MRI lumbar spine showed significant right paracentral L5-S1 disk prolapse indenting the thecal sac compressing the root. A full-course and effective medical treatment was initiated as the patient was never treated properly before for her back pain, along with physical therapy and regular OPD follow-ups. A follow-up MRI a year later revealed significant reduction in the size of the disk prolapse as compared to the initial imaging study. Overall, patient’s symptoms significantly improved, and she was kept on conservative management. Conclusion: To conclude, the case presented here shows the efficacy and validity of conservative management for patients who are diagnosed with a herniated disc in the absence of neurological deficits. This shows the importance of not pushing surgical treatment for patient with lumbar disc herniation without neurological deficits, each patient should receive a trial of conservative therapy and close OPD follow-ups and repeated MRI scans for further assessment of any advancement or improvement, because herniated discs can regress spontaneously. Radiological changes alone should not be the main target for assessing improvement, what matters more is clinical and symptomatic improvement. Surgical management remains an important therapeutic option for patients who failed conservative management and patients who have severe neurological deficits.


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