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This study examines the efficacy and safety of condoliase chemonucleolysis (CC) in treating lumbar disc herniation (LDH) and highlights emerging alternatives like chondroitin sulfate ABC endolyase. Research indicates that condoliase, an enzyme used to degrade glycosaminoglycans in the nucleus pulposus, provides effective and prompt relief of leg pain, with significant reductions observed within a day of treatment. Studies reveal that a lower pretreatment straight leg raising (SLR) angle may predict early symptom relief, and condoliase is generally effective at doses up to 1.25 U, balancing efficacy and safety. Despite promising results, concerns about long-term safety, including disc height reduction and imaging changes, persist. Additionally, chondroitin sulfate ABC endolyase shows potential as a safer and more effective alternative, though further research is needed to optimize treatment protocols and assess long-term outcomes. Future investigations should address current limitations, such as small sample sizes and short follow-up periods, to better understand the long-term benefits and risks of these treatments.

Lumbar disc herniation (LDH) is often managed surgically. Enzymatic chemonucleolysis emerged as a non-surgical alternative. This systematic review and meta-analysis aims to assess the efficacy and safety of chemonucleolytic enzymes for LDH. The primary objective is to evaluate efficacy through “treatment success” (i.e., pain reduction) and severe adverse events (SAEs) rates. Additionally, differences in efficacy and safety trends among chemonucleolytic enzymes are explored. Following our PROSPERO registered protocol (CRD42023451546) and PRISMA guidelines, a systematic search of PubMed and Web of Science databases was conducted up to July 18, 2023. Inclusion criteria involved human LDH treatment with enzymatic chemonucleolysis reagents, assessing pain alleviation, imaging changes, and reporting on SAEs, with focus on allergic reactions. Quality assessment employed the Cochrane Source of Bias and MINORS tools. Meta-analysis utilized odds ratios (OR) with 95% confidence intervals (CI). Among 62 included studies (12,368 patients), chemonucleolysis demonstrated an 79% treatment success rate and significantly outperformed placebo controls (OR 3.35, 95% CI 2.41–4.65) and scored similar to surgical interventions (OR 0.65, 95% CI 0.20–2.10). SAEs occurred in 1.4% of cases, with slightly higher rates in chymopapain cohorts. No significant differences in “proceeding to surgery” rates were observed between chemonucleolysis and control cohorts. Limitations include dated and heterogeneous studies, emphasizing the need for higher-quality trials. Further optimization through careful patient selection and advances in therapy implementation may further enhance outcomes. The observed benefits call for wider clinical exploration and adoption. No funding was received for this review.

Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis. Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%–81%], the proportion of surgery was 9% (95% CI 7%–12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%–47%), and the adverse events were 4% (95% CI 2%–6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) −2.46, 95% CI −3.30 to −1.63] and the herniated mass volume change (SMD −16.97, 95% CI −23.92 to −10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60–3.85). The results of sensitivity and publication bias analyses showed that the results were robust. Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492 , PROSPERO (CRD42022375492).

Lumbar disc herniation (LDH) represents a significant cause of pain and physical impairment, negatively impacting the quality of life, and burdening healthcare systems. Despite numerous treatment strategies, optimal management remains a subject of debate. This meta-analysis aims to compare the efficacy and economic impact of chemonucleolysis (CN) and discectomy in the management of LDH. An extensive search of Embase, PubMed, and Cochrane databases yielded 391 records. Following strict inclusion and exclusion criteria, twenty-one studies suitable for a comparative analysis between CN and discectomy were included. This selection was based on patient improvement, including pain scores, complications, and differences in cost and surgery time. A total of 2436 patients were included in this study. Among them, 1,121 patients (46%) underwent discectomy, while 1,315 patients (54%) received the CN approach. Our analysis revealed that discectomy had a significantly higher improvement rate compared with chymopapain CN (OR: 0.45; 95%CI 0.23,0.88) and non-chymopapain CN (OR: 0.61; 95%CI 0.38,0.97). A non-significant inclination towards complication rates was observed with chymopapain CN (OR: 1.90; 95%CI 0.68,5.29). Notably, CN was associated with a considerable cost reduction (SMD: 7.11; 95%CI -11.37,-2.85) and a shorter surgical time (MD: -53.54; 95%CI -57.91,-49.17) compared with discectomy. The evidence synthesized in this meta-analysis suggests superior clinical outcomes for discectomy when compared to CN in managing LDH. However, CN demonstrated a notable advantage in terms of cost-efficiency and operative time, marking it as a potentially preferable option in resource-constrained settings. Nonetheless, more randomized clinical trials and prospective studies are necessary to confirm these findings.

Background Condoliase is a treatment for lumbar disc herniation. This enzyme exerts its medicinal effects by digesting chondroitin sulfate (CS), which is abundant in the nucleus pulposus. However, the behavior of administered condoliase in the nucleus pulposus is not clear. Because the purpose of this study is to understand the mechanism of enzyme action, we evaluated the properties of condoliase in the nucleus pulposus. Methods The following were evaluated: (1) The diffusibility of fluorescein labeled condoliase injected into isolated porcine nucleus pulposus. (2) The time dependence of condoliase activity in porcine nucleus pulposus or CS solution. (3) The morphology of the enzyme‐treated nucleus pulposus tissue was characterized using scanning electron microscopy. Results After injection into the nucleus pulposus, condoliase was difficult to diffuse spontaneously, and the rate of CS‐disaccharides production was significantly increased up to a peak at 24 h and decreased thereafter. Not all of the CS in the nucleus pulposus was digested by condoliase. These results suggested that condoliase digested CS locally without causing its spontaneous diffusion within the nucleus pulposus. Moreover, condoliase did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus. Conclusions We demonstrated that condoliase is retained in the nucleus pulposus and exerts its pharmacological effects by locally degrading CS without degrading collagen fibers. The results obtained in this study can be useful in predicting the mechanism of the pharmacological action of condoliase in clinical practice. Condoliase digested chondroitin sulfate locally, and did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus.

Surgery is often the treatment of choice for lumbar disc herniation (LDH) with severe leg pain. This study aimed to investigate the efficacy of Condoliase chemonucleolysis (CC) in patients who were nonambulatory because of severe leg pain. A total of 58 patients who underwent CC for conservative treatment-resistant LDH were included in this study. Changes in the leg and lower back pain evaluated using the numeric rating scale (NRS) were retrospectively assessed at three time points (1 week, 1 month, and 3 months after treatment). Patients were divided into the ambulatory group (group A) and nonambulatory group (group N) based on their ambulatory status. The clinical and radiological findings including magnetic resonance images were compared between the two groups. Of the 58 patients, 16 (28%) who could not walk independently because of severe leg pain were included in group N. Group N showed significantly higher mean NRS score for leg pain (NRS-LP) before treatment than group A (group N, 7.9; group A, 6.8; p  = 0.009). Changes in the mean NRS-LP from pretreatment to 1 week were significantly higher in group N (group N, 5.2; group A, 3.4; p  = 0.02). In group N, the mean NRS-LP decreased significantly over time, and 69% of the patients were ambulatory after 1 week, 88% after 1 month, and 94% after 3 months. CC provides early pain relief and can be an immediate treatment option for patients who cannot walk independently because of severe leg pain.

Introduction Treatment of lumbar disc herniation (LDH) using condoliase chemonucleolysis (CC) requires more time than surgery to demonstrate therapeutic effects. This study aimed to identify patients who show significant improvement in leg pain very early after CC and to determine pretreatment factors that can predict a very early therapeutic response. Methods The study included 52 patients who underwent CC for treatment-resistant LDH. Scores for low back and leg pain measured by a numerical rating scale were assessed at four time points (1 day, 1 week, 1 month, and 3 months after CC). Patients who reported subjective pain relief the day after treatment and further exhibited an improved straight leg raising (SLR) angle compared to pretreatment were classified as “very early responders (VER)”. Results Of the 52 patients, 39 (75%) were VER, and 13 (25%) were non-VER. The VER showed earlier improvement in leg pain. The VER had a significantly higher proportion of positive SLR test patients ( p  = 0.01) and a significantly smaller pretreatment SLR angle compared to the non-VER (VER vs. non-VER: 40.6 ± 19.0 vs. 63.1 ± 16.9, p  < 0.001). There were no significant differences in the level, type, and size of LDH and the disc regression rate between the two groups. Conclusions Patients with a smaller pretreatment SLR angle are more likely to experience very early or early symptomatic relief, with a significant and sustained reduction in leg pain up to 3 months after CC treatment.

Lumbar disc herniation (LDH) is a leading cause of radicular pain and disability. While conventional intradiscal collagenase chemonucleolysis (ICCN) is a minimally invasive alternative to surgery, it is limited by suboptimal drug targeting and recurrence. Catheter-based extradural collagenase chemonucleolysis (CECCN) was developed to deliver the enzyme directly to the herniated fragment. This research aimed to compare the clinical efficacy and safety of CECCN versus ICCN. A total of 300 patients with single-level, symptomatic lumbar disc herniation refractory to conservative treatment were included. The CECCN group ( = 150) consisted of patients prospectively enrolled between January 2025 and December 2025. Data for this group were provided by five centers: the Department of Pain, The Second Affiliated Hospital of Guizhou Medical University ( = 70), the Department of Pain, Affiliated Hospital of Guizhou Medical University ( = 20), the Department of Pain, Affiliated Hospital of Zunyi Medical University ( = 20), the Department of Pain, Guiyang Fourth People's Hospital ( = 20), and the Department of Rehabilitation, Tianzhu County People's Hospital ( = 20). The ICCN group ( = 150) was established through retrospective review of medical records of patients who underwent conventional ICCN at the Department of Pain, The Second Affiliated Hospital of Guizhou Medical University between January 2023 and December 2024, met the same inclusion and exclusion criteria, and completed the predefined outcome assessments at the required follow-up time points. The outcomes were operation time, hospital stay, pain severity, lumbar function, clinical efficacy, quality of life and complications. Operation time was longer in the CECCN group (  < 0.01), but hospital stay was comparable (  > 0.05). The CECCN group demonstrated significantly lower NRS scores at 7 days, 1, 3, as well as 6 months (all  < 0.05). At 3 and 6 months, the CECCN group also showed superior JOA scores (  < 0.05), lower ODI scores (p < 0.05), a higher excellent/good rate per Macnab criteria (  < 0.05), as well as better SF-36 scores (  < 0.05) relative to the ICCN group. The occurrence of complication rate presented significantly lower in the CECCN group (  < 0.05). CECCN is more effective than conventional ICCN for relieving pain, improving function and quality of life, and reducing complications in LDH patients. The superior outcomes support its role as an advanced percutaneous treatment option, despite a longer procedural time.

Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan. This study investigated clinical and radiographic outcomes three months after the administration because the secondary surgical removal is most required during this period for the insufficient pain relief, and analyzed whether the differences of intradiscal injection areas affected the clinical outcomes. We retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. Postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas.

Study Design Retrospective cohort study. Objective Condoliase is a chemonucleolysis for lumbar disc herniation (LDH) that enzymatically degrades herniated disc material with high specificity for chondroitin sulfate and hyaluronic acid. Few studies have compared condoliase treatment with surgical treatments. We compared the clinical outcomes of condoliase treatment and minimally invasive discectomy. Methods Patients who received condoliase treatment or minimally invasive discectomy at single institution were included. Propensity score matching was performed to adjust for age and sex. We included 146 patients with LDH (73 per group). The Japan Orthopaedic Association (JOA) score, visual analog scale (VAS) for leg pain, and disc height and degeneration were assessed at baseline and 2 weeks, 3 months, and 1 year after treatment. Results The JOA score and leg pain VAS improved significantly over time (P < .001, Friedman’s test). Two weeks after treatment, a marked improvement in JOA score and leg pain VAS was observed in the surgery group compared with the condoliase group (P < .001, mixed-effects model). However, 3 months and 1 year after treatment, the differences were not significant. In contrast, disc height reduction was significantly greater in the condoliase group than in the surgery group at 3 months and 1 year after treatment (P < .001, mixed-effects model). Condoliase treatment was identified as an independent risk factor for progression of disc degeneration (odds ratio, 23.60; P = .001, logistic regression analysis). Conclusion Condoliase treatment demonstrated mid-term efficacy comparable to surgical treatment; however, it required more time for pain relief and was potentially associated with progression of disc degeneration.