Immediate Effects, Detailed Clinical Outcomes, and Prognostic Factors of Chemonucleolysis Using Condoliase for Lumbar Disc Herniation.

Chemonucleolysis utilizing condoliase is a minimally invasive treatment for lumbar disc herniation (LDH) aimed at reducing intervertebral disc pressure and enhancing symptoms. In this study, lower limb pain was measured using the numeric rating scale (NRS) the day after treatment and 1 and 3 months after treatment. Prognostic factors were assessed, categorizing participants into an improvement group (I-group) for NRS lower limb pain scores of ≥3.5 and a non-improvement group (N-group) for scores of <3.5. This study included a total of 225 patients treated between April 2020 and March 2023. The mean age was 46.5 ± 16.5 years, with 151 males. The mean duration of illness was 6.2 ± 8.52 months. As of the day after treatment, 60 cases were classified into the I-group, 118 cases at 1 month after surgery, and 152 cases at 3 months after surgery. The disease duration before treatment was significantly shorter in the I-group at 1 (8.19 ± 8.74 [I-group] vs. 5.17 ± 8.04 [N-group] months) and 3 months (8.51 [I-group] ± 7.35 vs. 5.69 ± 8.87[N-group] months) after treatment. The comparison of baseline leg pain NRS shows a difference in leg pain NRS in the I-group when compared on the day after treatment (6.02 ± 2.64 [I-group] vs. 7.50 ± 1.79 [N-group]), 1 (5.13 ± 2.69 [I-group] vs. 7.58 ± 1.66 [N-group]), and 3 months (4.42 ± 2.70 [I-group] vs. 7.34 ± 1.77 [N-group]). Chemonucleolysis using condoliase for LDH can improve symptoms the day after treatment and can be a minimally invasive treatment to avoid surgery.

Association of STAT3, CYP3A5, and ABCG2 Polymorphisms With Osimertinib-induced Adverse Events in NSCLC Patients.

BACKGROUND/AIM: Osimertinib is a key drug for treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Genetic differences may be associated to adverse events (AEs) induced by osimertinib. This retrospective observational multicenter study evaluated the association of genotypes, including STAT3 -1697C>G, CYP3A5 6986A>G, and ABCG2 421C>A, with the incidence of osimertinib-induced AEs in patients with EGFR mutation-positive NSCLC. PATIENTS AND METHODS: A total of 85 patients treated with osimertinib (Institution A: 33 patients, Institution B: 52 patients) were enrolled in the study. Single nucleotide polymorphisms were determined by real-time PCR, and the incidence of AEs was compared for each genotype. RESULTS: Paronychia incidence was 59% for the CC genotype, 19% for the CG genotype, and 19% for the GG genotype at STAT3 -1697C>G. A genotype-related trend was observed (Cochran-Armitage test, p=0.009). Multivariate analysis showed that the CC genotype at STAT3 -1697C>G and female sex were significant independent factors associated with paronychia [odds ratio (OR)=6.41, 95% confidence interval (CI)=1.94-21.20 and OR=3.40, 95%CI=1.03-11.22, respectively]. The incidence of diarrhea was 53% for the CC genotype, 30% for the AC genotype, and 29% for the AA genotype at ABCG2 421C>A, and a genotype-related trend was observed (p=0.048). However, the CC genotype at ABCG2 421C>A was not a significant independent factor associated with diarrhea in multivariate analysis. No significant associations were detected between other polymorphisms and the incidence of AEs. CONCLUSION: STAT3 -1697C>G may be a novel risk factor for osimertinib-induced paronychia in patients with NSCLC.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Usefulness of Preoperative Planning by Three-Dimensional Planning Software for Pedicle Screw Placement in Thoracolumbar Surgeries: Misplacement Rate and Associated Risk Factors.

Introduction: A number of imaging technologies have been developed to reduce the risk of pedicle screw (PS) misplacement. For example, preoperative three-dimensional (3D) planning can reportedly enhance implant placement accuracy in some orthopedic surgeries. However, no study has investigated the effect of preoperative 3D planning on PS placement without intraoperative 3D navigation. Thus, in this study, we aim to examine the accuracy of PS placement and identify the risk factors for PS misplacement in thoracolumbar surgeries performed using preoperative 3D planning software with intraoperative fluoroscopic guidance in a retrospective study. Methods: In total, 25 consecutive patients (197 PSs) underwent thoracic or lumbar spinal fusion surgeries using preoperative 3D planning with intraoperative fluoroscopic guidance. PS misplacement was graded based on the degree of perforation (Grade 0, no perforation; Grade 1, <2 mm; Grade 2, 2-4 mm; Grade 3, >4 mm) observed in postoperative computed tomography (CT). Deviations between planned and actual PSs were evaluated by matching preoperative and postoperative CT volume images for each vertebra. Results: The overall PS misplacement rate was 6.6% (Grade 1: 4.0%, Grade 2: 1.5%, Grade 3: 1.0%). The median linear deviations of PS entry points between planned and actual locations were determined to be 3.3 mm and 3.3 mm for the horizontal and vertical axes, respectively. The median angular deviations of the PS axis were 6.2° and 4.5° for the transverse and sagittal planes, respectively. Multivariate analysis revealed that horizontal deviation of the PS entry point was the sole factor associated with Grade ≥1 PS misplacement (odds ratio=2.47, p<0.001). Conclusions: Preoperative 3D planning software without intraoperative 3D navigation was able to achieve a relatively low PS misplacement ratio among the reported ratio of conventional techniques without navigation. Surgeons should carefully ensure that the entry point is consistent with preoperative planning, especially in the mediolateral direction to avoid misplacement in this method.

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia.

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily administration by percutaneous injection. FGFR inhibitor compounds are other drug candidates for achondroplasia because they directly fix the mutant protein malfunction. Although FGFR inhibitors elongate the bone of model mice, their adverse effects are not well studied. In this study, we found that a new FGFR inhibitor, ASP5878, which was originally developed as an anti-cancer drug, elongated the bone of achondroplasia model male mice at the dose of 300 µg/kg, which confers an AUC of 275 ng·h/ml in juvenile mice. Although ASP5878 was less effective in bone elongation than a CNP analogue, it is advantageous in that ASP5878 can be administered orally. The AUC at which minimal adverse effects were observed (very slight atrophy of the corneal epithelium) was 459 ng·h/ml in juvenile rats. The positive discrepancy between AUCs that brought efficacy and minimal adverse effect suggests the applicability of ASP5878 to achondroplasia in the clinical setting. We also analyzed effects of ASP5878 in a patient-specific induced pluripotent stem cell (iPSC) model for achondroplasia and found the effects on patient chondrocyte equivalents. Nevertheless, cautious consideration is needed when referring to safety data obtained from its application to adult patients with cancer in clinical tests.

Does sagittal imbalance impact the surgical outcomes of short-segment fusion for lumbar spinal stenosis associated with degenerative lumbar scoliosis?

BACKGROUND: The degenerative lumbar scoliosis (DLS) patients who mainly complained about neurogenic claudication due to spinal canal stenosis are well-indicated for short segment fusion (SSF) at the affecting levels. However, it is unclear whether we should consider global sagittal balance or not. The aim of this study was to evaluate the impact of sagittal balance on the surgical outcomes of degenerative lumbar scoliosis (DLS) patients who underwent SSF. METHODS: We retrospectively reviewed 70 DLS patients who underwent SSF (less than 3 levels) and could be followed for at least 2 years. The PI-LL, PT, SVA, and T1 pelvic angle (TPA) were measured using standing whole spine X-rays preoperatively (PreO) and at final follow-up (FFU). Surgical outcomes were assessed with the improvement in Japanese Orthopaedic Association score (JOAs) for low back pain (LBP), and the level of LBP was measured using the visual analogue scale (LBP-VAS). We analysed the relationships between the radiographic parameters and the surgical outcomes. RESULTS: We divided the patients into the three groups (poor/fair/good) based on the JOAs. The analysis with the Jonckheere-Terpstra trend test indicated that the following radiographic parameters had a significant trend with surgical outcomes in each group: (poor/fair/good; p value); PreO PI-LL (26/20/17°; P = 0.04), SVA (46/75/35.5 mm; P = 0.02), TPA (28/27/23°; p = 0.04), FFU PI-LL (33/25/8.5°; P = 0.004), SVA (93/90.5/32.5 mm; P = 0.001), and TPA (33/29/25°; P = 0.007). Additionally, LBP-VAS had a significant correlation between the three groups at final follow-up (P = 0.004). There were significant correlations between improvement in JOAs and PI-LL, SVA, and TPA both PreO and at FFU (P < 0.05). CONCLUSIONS: Sagittal spinal imbalance and spinopelvic malalignment significantly impact the surgical outcomes of SSF for DLS. Preoperative evaluation of spinopelvic alignment and sagittal balance is of critical importance when SSF are performed for DLS patients.

Posterior corrective surgery with a multilevel transforaminal lumbar interbody fusion and a rod rotation maneuver for patients with degenerative lumbar kyphoscoliosis.

The purpose of this study was to assess the clinical results of posterior corrective surgery using a multilevel transforaminal lumbar interbody fusion (TLIF) with a rod rotation (RR) and to evaluate the segmental corrective effect of a TLIF using CT imaging. The medical records of 15 consecutive patients with degenerative lumbar kyphoscoliosis (DLKS) who had undergone posterior spinal corrective surgery using a multilevel TLIF with an RR technique and who had a minimum follow-up of 2 years were retrospectively reviewed. Radiographic parameters were evaluated using plain radiographs, and segmental correction was evaluated using CT imaging. Clinical outcomes were evaluated with the Scoliosis Research Society Patient Questionnaire-22 (SRS-22) and the SF-36. The mean follow-up period was 46.7 months, and the mean age at the time of surgery was 60.7 years. The mean total SRS-22 score was 2.9 before surgery and significantly improved to 4.0 at the latest follow-up. The physical functioning, role functioning (physical), and social functioning subcategories of the SF-36 were generally improved at the latest follow-up, although the changes in these scores were not statistically significant. The bodily pain, vitality, and mental health subcategories were significantly improved at the latest follow-up (p < 0.05). Three complications occurred in 3 patients (20%). The Cobb angle of the lumbar curve was reduced to 20.3° after surgery. The overall correction rate was 66.4%. The pelvic incidence-lumbar lordosis (preoperative/postoperative = 31.5°/4.3°), pelvic tilt (29.2°/18.9°), and sagittal vertical axis (78.3/27.6 mm) were improved after surgery and remained so throughout the follow-up. Computed tomography image analysis suggested that a 1-level TLIF can result in 10.9° of scoliosis correction and 6.8° of lordosis. Posterior corrective surgery using a multilevel TLIF with an RR on patients with DLKS can provide effective correction in the coronal plane but allows only limited sagittal correction.

Biological oxidation of Mn(II) coupled with nitrification for removal and recovery of minor metals by downflow hanging sponge reactor.

Biogenic manganese oxides (bio-MnO2) have been shown to absorb minor metals. Bioreactor cultivation of heterotrophic manganese oxidizing bacteria (MnOB), which produce bio-MnO2 via oxidation of Mn (II), can be expected to be involved in a promising system for removal and recovery of minor metals from wastewater. However, MnOB enrichment in wastewater treatment is difficult. This study investigated whether MnOB can be cultivated when coupled with nitrification in a system in which soluble microbial products (SMP) from nitrifiers are provided to MnOB as a substrate. A downflow hanging sponge (DHS) reactor was applied for MnOB cultivation with ammonium (NH4⁺) and Mn (II) continuously supplied. During long-term operation, Mn (II) oxidation was successfully established at a rate of 48 g Mn m⁻³ d⁻¹ and bio-MnO2 that formed on the sponges were recovered from the bottom of the reactor. The results also revealed that Ni and Co added to the influent were simultaneously removed. Microbial 16S rRNA gene clone analysis identified nitrifiers supporting MnOB growth and showed that only one clone of Bacillus subtilis, which was affiliated with a known MnOB cluster, was present, suggesting the existence of other novel bacteria with the ability to oxidize Mn (II).