måndag 19 februari 2024

Länkar mm forskning modicförändringar

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2008: H B Albert. mfl

Conclusions: 
In this uncontrolled trial, the clinical effect of antibiotic treatment was large in a group of patients with Modic changes suffering from persistent LBP following a disc herniation. These results provide tentative support for a hypothesis that bacterial infection may play a role in LBP with Modic changes and indicate the need for randomised controlled trials to test this hypothesis.
 
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2013. H B Albert. mfl 

Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy
 
Conclusions:
The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.
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2014 Mohammed A. mfl

 
Conclusions:
The antibiotic protocol in this study was more effective for this group of patients (CLBP associated with Modic changes type I) than placebo in the outcomes.
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2014 Claus Manniche 

"Vertebral endplate (modic) changes and the treatment of back pain using antibiotics"

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2017 S. Magnitsky, S. Dudli, mfl
 
 
Conclusion.  
The 1.05 ppm NMR signal from PA can be used as a marker of P. acnes infection of discs. This signal does not overlap with other disc metabolites and linearly depends on P. acnes concentration. Consequently, NMR spectroscopy may provide a noninvasive method to detect disc infection in the clinical setting. 
 
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2017 Manu N Capoor  Mfl
 
Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy 
 
Conclusions: 
This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination.

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2018. Magnitsky, Sergey PhD∗ mfl
 
Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the Tissue With Propionibacteria acnes Bacteria
 
Conclusion: 
The 1.05 ppm NMR signal from PA can be used as a marker of P. acnes infection of discs. This signal does not overlap with other disc metabolites and linearly depends on P. acnes concentration. Consequently, NMR spectroscopy may provide a noninvasive method to detect disc infection in the clinical setting.
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2018: Guoqing Tang mfl
 
Latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs

Conclusions: Our findings further validated the presence of low-virulence anaerobic bacteria in degenerated IVDs, and P. acnes was the most frequent bacterium. In addition, the latent infection of bacteria in IVDs was associated with Modic changes. Therefore, low-virulence anaerobic bacteria may play a crucial role in the pathophysiology of MCs and lumbar disc herniation. 
 
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2019: Lars Christian Haugli Bråten mfl 
 
Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

In this paper by Bråten and colleagues (BMJ 2019;367:l5654, doi:10.1136/bmj.l5654, published 16 October 2019), an error was spotted in table S6 of the supplementary appendix, describing post hoc analyses. In the descriptive part of type 1 Modic changes, the numbers for the amoxicillin and placebo groups at 12 months had been swapped erroneously. A corrected appendix will be uploaded in due course.
 
 https://www.bmj.com/content/368/bmj.m546
 
 

The error, of placing data in the wrong group, made by the authors is an unusual one. On re-reading the original article published in the BMJ last year and the supplementary appendix which was not readily available it seems as if there have been further errors of omission and misleading conclusions.

In table S6: primary and secondary outcomes for separate Modic change types, the data clearly shows that the Modic 1 group improved by more than 4 points on the Roland Morris disability questionnaire (4.7) reaching p value of 0.02. It also shows a mean difference of 5 points on the Oswestry scale compared to placebo.

The authors state clearly that the minimum clinically important difference widely accepted for the RMDQ is 4 points.

In other words, this trial showed a benefit for patients with Modic type 1 change, whereas the authors concluded it did not because they conflated the results with patients with type 2 Modic change.

Braten states in the introduction the intention was to replicate the earlier trial by Albert which was done on only Type 1 patients, but half his study population had Type 2 changes.

Furthermore they did not chose amoxicilllin - clavulinate (more effective against anaerobic bacteria like Propriobacter acne) but amoxicillin alone.

Hanne Albert & Claus Manniche kommenterar:
 
 
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2020: Lorenzo Drago mfl

Are Modic type 2 disc changes associated with low-grade infections? A pilot study

Conclusions: 
Although performed in a limited series of patients, this study supports the hypothesis that some cases of Modic 2 changes might be associated with the presence of low virulent bacteria.
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Conclusion:  
Our study confirms that MC represents an intense inflammatory status and activation of host defense response and immunological pathways. Downstream effects leading to ubiquitin mediated proteasomal degradation of ECM proteins and the resulting metabolites such as glutamic acid could cause excessive pain and needs further investigation. 
 
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Evidence for infection in intervertebral disc degeneration: a systematic review

Conclusion:  
Evidence to date implicates C. acnes identified through culture, microscopy and sequencing, with some suggestion of diverse bacterial colonisation in the disc. This review found studies which used culture methods and conventional PCR for bacterial detection. Further agnostic investigation using newer methods should be undertaken.
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2021: C. Manniche

Conclusion:
New compelling microbiological studies of the past 5 years, combined with enhanced imaging technologies, have led to a better understanding of the now definitively demonstrated infectious pathway leading to MC and CLBP. This update review included two high-quality RCTs, one small RCT without follow-up data, a post hoc subgroup analysis and several open-label studies of varying sizes. All three RCTs demonstrated statistically significant results for patients with CLBP and MC1 on their MRI scans after undergoing long-term oral antibiotic treatment.
 
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2022: Yucheng Jiao mfl
 
Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway
 
Therefore, P. acnes had a strong association with LBP by stimulating NPCs to secrete NGF via the TLR2-NF- κB/JNK or ROS-related pathway
 
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This analysis suggested that oral Q12h doses of amoxicillin of up to 1000 mg are unlikely to reach antibacterial herniated disc tissue exposure. The 500 mg or 750 mg amoxicillin Q8h mean exposure may be effective for 50% of C. acnes strains, and the 1000 mg Q8h mean exposure may be effective for 90% of C. acnes strains. These were the mean exposures. Given that oral amoxicillin pharmacokinetics are variable, some disc tissues will at times contain no detectable amoxicillin, and that disc tissues evaluated to date may not reflect concentrations in the core of the nucleus pulposus, it is possible that all oral amoxicillin CLBP studies to date have been underdosed, and that the variability in terms of clinical effect is due to the wide variability in amoxicillin exposure at the site of infection. Disc amoxicillin is essentially eliminated during a single dose interval and it is not known if there is any accumulation in tissue concentration with multiple daily doses for up to 100 days. A wide range of amoxicillin exposures to disc tissue can be expected throughout the duration of up to 100 days of Q8h regimens, with a total of up to 300 doses.
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2023: Xiaolong Chen mfl
 
The association between low virulence organisms in different locations and intervertebral disc structural failure: A meta-analysis and systematic review

Conclusion:
Compared with the patients without endplate change, the patients with endplate changes had higher rates of microbial colonization of disc. The primary pathogen was Cutibacterium acnes which was present in 22.2% of cases. This meta-analysis and systematic review found low-quality grade evidence for an association between microbial colonization of disc with endplate changes. The primary pathogen was C. acnes.
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 2024: I. Heggli.mfl
Conclusion:
Our study provides the first evidence for the existence of bacterial (C.acnes “high”) and non-bacterial (C.acnes “low”) subtypes in MC1 patients with CLBP. This supports the need for different treatment strategies.
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