Authors: Kevin Pauza, MD , Kwadwo Boachie-Adjei, BS , Patrick Ercole, PhD , Francis Hussey, IV, MS , Joseph Nguyen, MPH , Akua Serwaa-Sarfo, MPH , Jacob Sutton, MD , Carrie Wright, MD, MS , William Delany Murrell, MD, MS
MANUSCRIPT NUMBER:
PAINPHYSICIAN-D-23-00261R1
FULL TITLE:
Long-term Investigation of Annulargrams, Intra-annular Fibrin Treat Chronic Discogenic LBP-Radiculopathy: 1-3 Year Outcomes Comparisons Patients with and without Prior Surgery
KEYWORDS:
low back, radiculopathy, fibrin, disc herniation, degenerative disc, regenerative, annulargram, annulogram
CORRESPONDING AUTHOR’S INSTITUTION:
Infohealth LLC
BACKGROUND:
Discogenic chronic low back pain (cLBP) and radiculopathy are the most prevalent causes of disability worldwide. Prior spine treatments often lack reliability and are associated with adverse events. Among surgical treatment options, discectomies weaken discs to cause accelerated degeneration, and fusions directly cause damaging forces against adjacent discs accelerating their degeneration. Other regenerative medicine treatments including “stem cell” centrifuged bone marrow aspirate (BMC),and Platelet-Rich Plasma (PRP), lack fibrin’s bio-adhesive properties. Specifically, fibrin is a strong bio-adhesive and it immediately integrates into disc defects and binds, becomes part of the disc to facilitate new disc tissue growth.
OBJECTIVES:
Evaluate the safety and efficacy of this new pragmatic algorithm which both diagnoses and treats chronic low back pain by (i) identifying Annulus Fibrosus tears (fissures) region of symptoms, and (ii) treating those tears with fibrin, sealing them and facilitating new tissue growth.
STUDY DESIGN:
Retrospective cohort study that prospectively reported validated Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation measures in a registry.
SETTING:
Private, single center, specialized, interventional pain management institution
METHODS:
Subjects suffer with cLBP with or without radiculopathy for greater than six months. Prior to enrollment, all subjects underwent physical therapy and at least four invasive treatments without relief. Failed treatments included BMC or PRP injections, intradiscal or intra-articular into zygapophyseal joints, or combinations of both.
Additional failed treatments included fluoroscopically guided epidural corticosteroids or PRP, or Medial Branch radiofrequency neurotomies. Diagnostic certainty of underlying condition was confirmed by screening MRIs (1.5T) and plain-film radiographs performed six months prior to treatment and confirmed in 100% of patients enrolled, without concomitant conditions: (i) carcinoma, (ii) fracture, (iii) instability, or (iv) severe vertebral canal or intervertebral foramen stenosis.
OUTCOMES ASSESSMENT:
Oswestry Disability Index (ODI), Low Back and Leg Pain Visual Analog Scale (VAS), PROMIS Global Mental Health (GMH), Estimated Utility Score (EuroQol), and Modified North American Spine Society (NASS) Patient Satisfaction Survey.
RESULTS:
Significant Improvement was demonstrated at 1-, 2-, and 3-years post
treatment in all outcomes measures. Mean duration of low back pain prior to treatment was 11.2 years. Subject mean age 56 years, 30% female, 70% male. Both the failed surgery cohort and non-surgery cohort demonstrated significant improvement after fibrin treatment, with the failed surgery cohort realizing greater relative improvement. Significant Improvements in ODI, VAS, and PROMIS (Mental and Physical) were consistent across age, gender, co-morbidity and exposure status. At 12-month follow up, 50% of subjects achieved MCID utilizing ODI. No severe adverse events were reported.
LIMITATIONS:
Limitations include patient demographic factors, outcome-measure sensitivity, or that outcomes were reported prospectively and calculated retrospectively as 1-, 2-, and 3-year timeframes were attained. Although categorical analyses comparing prior surgical with non-surgical cohort was performed, pre-enrollment treatments were not categorized for comparison.
CONCLUSIONS:
Intra-annular fibrin bio adhesive sealant demonstrates ability as an effective treatment to alleviate discogenic cLBP and radiculopathy for at least three years, even in subjects who all failed multiple prior treatments, including discectomy, fusion, disc PRP or BMC. Results suggest benefit of fibrin sealant; however, future investigations to consider include a randomized double-blind controlled trial and further categorical analyses.
Discogenic cLBP and radiculopathy are the most common causes of disability worldwide. Unfortunately, most spine treatments tend to have low success rates and are associated with adverse effects.
Discectomies are known to weaken discs and cause accelerated degeneration. Spinal fusions directly cause damaging forces against adjacent discs and accelerate degeneration as well. Other biologic treatment options like “stem cell” centrifuged bone marrow aspirate (BMC), and Platelet-Rich-Plasma (PRP) lack bio-adhesive properties to seal and heal annular tears, a property of the fibrin used in the Discseel Procedure. Specifically, fibrin is a strong bio-adhesive and it immediately integrates into disc defects and binds, becoming part of the disc to facilitate new disc tissue growth.
Kevin Pauza, MD, and co-investigators have published a groundbreaking, long-anticipated study evaluating the safety and effectiveness of the Discseel Procedure in diagnosing and treating cLBP.
Following a group of 827 subjects over three years, no study of this size or length has ever been conducted to determine the effectiveness of biologic treatment for back pain. All of the 827 subjects selected had previously undergone treatment like physical therapy, discectomies, spinal fusions, and/or stem cell injections, and experienced no relief or worsened pain.
All subjects underwent the Discseel Procedure and at 12-month follow-up, 50% of subjects achieved significant relief from their pain and reduced disability, with no severe adverse effects reported. Additionally, subjects continued to demonstrate improvement at 2- and 3-years posttreatment in all outcomes measured.
This improvement was observed in both the failed surgery and non-surgery cohorts, with the failed surgery cohort reporting greater relative improvement. Pain relief was consistent across age, gender, co-morbidity, and exposure status.
This study concludes that Intra-annular fibrin bio-adhesive sealant demonstrates strong effectiveness in alleviating cLBP and radiculopathy, even in patients who failed multiple prior treatments and procedures.
Author(s): Kevin Joseph Pauza, Maxim Moradian, and Gregory Lutz
Introduction:
The DISCSEEL Procedure treats chronic low back and cervical disogenic pain, with or without extremity radiculopathy. The procedure is defined as a sequence of two steps: a diagnostic, nonprovocation Annulargram, followed by intra-annular injection of nonautologous fibrin into every morphologically abnormal disc (torn disc) and into the needle puncture holes created by the preceding diagnostic Annulargram.
Setting
Three centers in the United States.
Interventions
Volume- and pressure-controlled intradiscal delivery of BIOSTAT BIOLOGX® Fibrin Sealant with the Biostat® Delivery Device into the symptomatic lumbar disc(s).
Background context
Intradiscal electrothermal therapy (IDET) is a treatment for discogenic low back pain the efficacy of which has not been rigorously tested.
Purpose
To compare the efficacy of IDET with that of a placebo treatment.
Study design/setting
Randomized, placebo-controlled, prospective trial.
Patient sample
Patients were recruited by referral and the media. No inducements were provided to any patient in order to have them participate. Of 1,360 individuals who were prepared to submit to randomization, 260 were found potentially eligible after clinical examination and 64 became eligible after discography. All had discogenic low back pain lasting longer than 6 months, with no comorbidity. Thirty-seven were allocated to IDET and 27 to sham treatment. Both groups were satisfactorily matched for demographic and clinical features.
Methods
IDET was performed using a standard protocol, in which the posterior annulus of the painful disc was heated to 90 C. Sham therapy consisted of introducing a needle onto the disc and exposing the patient to the same visual and auditory environment as for a real procedure. Thirty-two (85%) of the patients randomized to the IDET group and 24 (89%) of those assigned to the sham group complied fully with the protocol of the study, and complete follow-up data are available for all of these patients.
Outcome measures
The principal outcome measures were pain and disability, assessed using a visual analog scale for pain, the Short Form (SF)-36, and the Oswestry disability scale.
Results
Patients in both groups exhibited improvements, but mean improvements in pain, disability and depression were significantly greater in the group treated with IDET. More patients deteriorated when subjected to sham treatment, whereas a greater proportion showed improvements in pain when treated with IDET. The number needed to treat, to achieve 75% relief of pain, was five. Whereas approximately 40% of the patients achieved greater than 50% relief of their pain, approximately 50% of the patients experienced no appreciable benefit.
Conclusions
Nonspecific factors associated with the procedure account for a proportion of the apparent efficacy of IDET, but its efficacy cannot be attributed wholly to a placebo effect. The results of this trial cannot be generalized to patients who do not fit the strict inclusion criteria of this study, but IDET appears to provide worthwhile relief in a small proportion of strictly defined patients undergoing this treatment for intractable low back pain.
Background context
In a small prospective study assessing 10 symptomatic and 10 asymptomatic subjects, Schellhas et al. compared cervical discography to magnetic resonance imaging. Within that study he reported on the distribution of pain for the C3–C4 to C6–C7 levels. Four years later, Grubb and Ellis reported retrospective data from his 12-year experience using cervical discography from C2–C3 to C7–T1 in 173 patients. To date, no large prospective study defining pain referral patterns for each cervical disc has been performed.
Purpose
To conduct a prospective visual and statistical descriptive study of pain provocation of a cohort of subjects undergoing cervical discography.
Study design/setting
Prospective multicenter descriptive study.
Methods
Pain referral maps were generated for each disc level from patients undergoing cervical discography with at least two levels assessed. If concordant pain was reproduced in a morphologically abnormal disc, the subject immediately completed a pain diagram. An independent observer interviewed the subject and recorded the location of provoked symptoms. Visual data were compiled using a body sector bit map, which consisted of 48 clinically relevant body regions. Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated.
Results
A total of 101 symptom provocation maps were recorded during cervical discography on 41 subjects. There were10 at C2–C3, 19 at C3–C4, 27 at C4–C5, 27 at C5–C6, 16 at C6–C7 and 2 at C7–T1. Predominantly unilateral symptoms were provoked just as often as bilateral symptoms. The C2–C3 disc referred pain to the neck, subocciput and face. The C3–C4 disc referred pain to the neck, subocciput, trapezius, anterior neck, face, shoulder, interscapular and limb. The C4–C5 disc referred pain to the neck, shoulder, interscapular, trapezius, extremity, face, chest and subocciput. The C5–C6 disc referred pain to the neck, trapezius, interscapular, suboccipital, anterior neck, chest and face. The C6–C7 disc referred pain to the neck, interscapular, trapezius, shoulder, extremity and subocciput. At C7–T1 we produced neck and interscapular pain. Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated.
Conclusions
In conclusion, these results confirm the observations of prior investigators that cervical internal disc disruption can elicit axial and peripheral symptoms. The particular patterns of pain generation allow the discographer to preprocedurally anticipate disc levels to assess. With these data, the number of disc punctures that are required can be limited rather than routinely assessing all cervical discs.
BACKGROUND CONTEXT:
Pathologic disc degeneration includes ineffective healing of tissue damage that accumulates over time. Regions of inflammation, neoinnervation, and nociceptor sensitization can lead to chronic discogenic pain. An important component of normal wound healing occurs when Fibrin interacts with matrix and cellular structures. The biostimulatory effects of fibrin include fibroblast recruitment, matrix synthesis, and granulation tissue formation. The Biostat Disc Augmentation System has been developed as a Fibrin-based treatment for discogenic pain.
Abstract
Study design: This prospective study evaluated the diagnostic utility of historically accepted sacroiliac joint tests. A multidisciplinary expert panel recommended 12 of the “best” sacroiliac joint tests to be evaluated against a criterion standard of unequivocal gain relief after an intra-articular injection of local anesthetic into the sacroiliac joint.
Objectives: To identify a single sacroiliac joint test or ensemble of test that are sufficiently useful in diagnosing sacroiliac joint disorders to be clinically valuable.
Summary of background data: No previous research has been done to evaluate any physical test of sacroiliac joint pain against an accepted criterion standard.
Methods: Historical data was obtained, and the 12 tests were performed by two examiners on 85 patients who subsequently underwent sacroiliac joint blocks. Ninety percent or more relief was considered a positive response, and less then 90% relief was considered a negative response.
Results: There were 45 positive and 40 negative responses. No historical feature, none of the 12 sacroiliac joint tests, and no ensemble of these 12 tests demonstrated worthwhile diagnostic value.
Conclusion: Sacroiliac joint pain is resistant to identification by the historical and physical examination data from tests evaluated in this study.
Abstract
The surfaces of annulus fibrosus tears are known harbingers of inflammatory constituents within intervertebral discs, stimulating sensitized nocioceptors within those tears. Other current treatment options of internal disc disruption neglect to specifically address the surface of these tears. Therefore, this investigation answers the question: does nonautologous Fibrin sealant applied to the surface of annulus fibrosus tears mechanically glue and seal annular tears? Regarding this query, results suggest nonautologous concentrated fibrin successfully seals annulus fibrosus tears with a “suture-like mechanical sealant,” serving as a safe option for treating symptomatic or nonsymptomatic intervertebral disc tears. Sealing tears prevents pain-generating chemicals of the nucleus pulposus from leaking through annular tears. More specifically, Fibrin sealant minimizes or eliminates extravasation of nucleus pulposus through tears and voids within the annulus fibrosus. Moreover, an investigation subjecting discs to an “internal pressure challenge” objectively affirms Fibrin’s ability to seal torn and degenerated discs against a pressure challenge. (1 psi ¼ 6.89476 kPs (disc mean pressure pretreatment ¼ 75.84 kPs; post-treatment ¼ 179.3 kPs: (n ¼ 347, P o 0.001). Therefore, sealing annular tears serves to minimize extravasation of the nucleus pulposus through annular tears, thus potentially treating symptoms caused by internal disc disruption, “Leaky Disc Syndrome,” and chemical radiculopathy. Additionally, sealing annular tears potentially allows adjunctive regenerative biologics such as mesenchymal precursor cells, platelet-rich plasma, and growth factors to remain within discs, thus, potentially optimizing their efficacy. A prior in vivo investigation demonstrated the vast majority of mesenchymal stem cells leaked from animal intravertebral discs, and another demonstrated radiolabeled mesenchymal stem cells leaked from degenerated discs and were subsequently found within new exuberant osteophytes adjacent to the degenerated disc. Intra-annular nonautologous concentrated Fibrin shares a benefit of other intradiscal biologics in that Fibrin does not cause aberrant detrimental mechanical forces on adjacent discs, compared with surgical fusion and disc arthrodesis, which both cause aberrant, potentially damaging mechanical forces on adjacent segments. The mean number of morphologically abnormal lumbar intervertebral discs in this population with chronic low back pain was 3.21 discs. & 2016 Published by Elsevier Inc.
Disclaimer : Disclaimer: All information presented in this website is intended for informational purposes only and not for the purpose of rendering medical advice. The information contained herein is not intended to diagnose, treat, cure or prevent any disease.
1333 3rd Avenue South, Suite 501,
Naples, Florida, 34102
Follow us to stay up to date on our groundbreaking procedures, news, speaking engagements and upcoming appearances.
Disclaimer : Disclaimer: All information presented in this website is intended for informational purposes only and not for the purpose of rendering medical advice. The information contained herein is not intended to diagnose, treat, cure or prevent any disease.
