Optimal Timing of Starting Growing Rod Treatment for Early-onset Scoliosis.

BACKGROUND CONTEXT: Growing rod (GR) systems require periodical surgical intervention and may cause associated complications, as well as worsened sagittal plane deformity. Generally, the risk of complications decreases with increment in age at the time of the index surgery with GR construct placement. However, the optimal timing to begin GR treatment has not reached a consensus yet. PURPOSE: This study was performed to investigate the effect of age at the index GR surgery on the complication rates and formulate clinical guidelines for the optimal timing to begin GR treatment for EOS patients. STUDY DESIGN: Kaplan-Meier analysis was used to determine complication occurrence as a function of the age at the index surgery and to determine the survival rates for the procedures. The receiver operator characteristic (ROC) curve was used to determine optimal cut-off values for the optimal timing of index surgery based on whether complication occurred or not. PATIENT SAMPLE: 54 patients who met the criteria were enrolled in this study. OUTCOME MEASURES: The following spinal parameters were measured: major coronal Cobb angle, global kyphosis (GK), and coronal balance (CB). CB was defined as the horizontal distance from the C7 plumb line to the center sacral vertical line. METHODS: All patients had completed GR treatment and had a minimum 1-year follow-up duration after the final surgical intervention. Patient data were collected as follows: age at the index surgery, gender, diagnosis, type of GR construct, and the number of lengthening procedures. The standing full-spine radiographs were obtained before and after the index surgery, before and after each lengthening procedures, before and after the final surgical intervention, and at the latest follow-up. Complications were categorized as implant, alignment, and general. RESULTS: Kaplan-Meier analysis of complications demonstrated a declining trend in complication rates with increasing age at the index surgery. The absence of perioperative complications was targeted, we constructed the ROC curve and the cut-off value was 71.0 months. Age at the index surgery was therefore categorized into two groups: younger-age group (≤ 71.0 months) and advanced-age group (> 71.0 months). There was a higher complication rate for the younger-age group than versus the advanced-age group (61.5% vs 22.0%, P=0.011). PJK as a major alignment-related complication, was more frequent in the younger-age group than in the advanced-age group (30.8% vs 4.9%, P=0.025). But the advanced-age group exhibited significantly more severe deformities before GR surgery compared to the younger-age group. CONCLUSIONS: This study shows that the elevated risk of complications observed in the younger-age group, which can be attributed to the younger age at the index surgery and the increased number of lengthening procedures during treatment. We suggest deferring the initiation of GR treatment until after the age of six years for EOS patients. We hope it will serve as a basis for GR technique in the treatment of EOS, with the ultimate goal of enhancing treatment outcomes for this challenging disorder.

Association Between Vertebral Endplate Defects and Patient-reported Symptoms: An Immunohistochemical Study Investigating the COX-2/PGE-2/EP-4 Axis.

BACKGROUND CONTEXT: Vertebral endplate defects are often implicated in degenerative disc disorders, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. PURPOSE: To investigate the association between endplate defects and patient-reported symptoms and to further clarify the role of the COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain. STUDY DESIGN/SETTING: Retrospective study PATIENT SAMPLE: A total of 71 patients who had undergone single-level L4/5 or L5/S1 modified laminectomy decompression preserving proximal upper laminae and transforaminal lumbar interbody fusion surgery were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. OUTCOME MEASURES: Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow-up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. METHODS: Patients were divided into Defect and Non-defect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, and then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the Defect group and Non-defect group. Data were analyzed using independent t-tests and χ² tests. Pearson's rank correlation test was used to assess correlations between patient-reported symptoms and the percentage of immune-positive cells in the groups. Multivariable logistic regression models using the forward stepwise likelihood ratio method were used to identify the factors that were independently associated with endplate defects. RESULTS: The age of Defect group was significantly higher than that of Non-defect group (52.5±7.7 vs. 57.2±9.1. P=0.024). There were no significant differences in gender, diagnosis, BMI, comorbidities, or surgical level between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than Non-defect group (38.5% vs. 11.1%, P<0.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs. 33.3%, P<0.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs. 4.9±1.6, P<0.001) and ODI scores (62.9±10.7 vs. 45.2±14.8, P<0.001) than Non-defect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized by upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in Defect and Non-defect groups, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both<0.001), PGE-2 (r=0.611; r=0.640, p both<0.001), and EP-4 (r=0.643; r=0.563, p both<0.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048∼2.171], P=0.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106∼1.508], P=0.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048∼2.171], P=0.003). CONCLUSIONS: Patients with endplate defects had worse quality of life, more severe disc degeneration and Modic changes, and up-regulated COX-2/PGE-2/EP-4 axis expression in cartilage endplates in patients with defected endplates. Inflammatory factors may significantly contribute to the onset and progression of chronic low back pain in patients with endplate defects, consequently impacting patient-reported symptoms.

Current examining methods and mathematical models of horizontal transfer of antibiotic resistance genes in the environment.

The increasing prevalence of antibiotic resistance genes (ARGs) in the environment has garnered significant attention due to their health risk to human beings. Horizontal gene transfer (HGT) is considered as an important way for ARG dissemination. There are four general routes of HGT, including conjugation, transformation, transduction and vesiduction. Selection of appropriate examining methods is crucial for comprehensively understanding characteristics and mechanisms of different HGT ways. Moreover, combined with the results obtained from different experimental methods, mathematical models could be established and serve as a powerful tool for predicting ARG transfer dynamics and frequencies. However, current reviews of HGT for ARG spread mainly focus on its influencing factors and mechanisms, overlooking the important roles of examining methods and models. This review, therefore, delineated four pathways of HGT, summarized the strengths and limitations of current examining methods, and provided a comprehensive summing-up of mathematical models pertaining to three main HGT ways of conjugation, transformation and transduction. Finally, deficiencies in current studies were discussed, and proposed the future perspectives to better understand and assess the risks of ARG dissemination through HGT.

Characteristics of soil nitrogen and phosphorus fractions and microbial traits with increasing stand age in two-layered Cunninghumia lanceolata + Phoebe bournei plantations.

Soil nitrogen and phosphorus are two key elements limiting tree growth in subtropical areas. Understanding the regulation of soil microorganisms on nitrogen and phosphorus nutrition is beneficial to reveal maintenance mechanism of soil fertility in plantations. We analyzed the characteristics of soil nitrogen and phosphorus fractions, soil microbial community composition and function, and their relationship across three stands of two-layered Cunninghumia lanceolata + Phoebe bournei with different ages (4, 7 and 11 a) and the pure C. lanceolata plantation. The results showed that the contents of most soil phosphorus fractions increased with increasing two-layered stand age. The increase in active phosphorus fractions with increasing stand age was dominated by the inorganic phosphorus (9.9%-159.0%), while the stable phosphorus was dominated by the organic phosphorus (7.1%-328.4%). The content of soil inorganic and organic nitrogen also increased with increasing two-layered stand age, with NH4+-N and acid hydrolyzed ammonium N contents showing the strongest enhancement, by 152.9% and 80.2%, respectively. With the increase of stand age, the composition and functional groups of bacterial and fungal communities were significantly different, and the relative abundance of some dominant microbial genera (such as Acidothermus, Saitozyma and Mortierella) increased. The relative abundance of phosphorus solubilization and mineralization function genes, nitrogen nitrification function and aerobic ammonia oxidation function genes tended to increase. The functional taxa of fungi explained 48.9% variation of different phosphorus fractions. The conversion of pure plantations to two-layered mixed plantation affected soil phosphorus fractions transformation via changing the functional groups of saprophytes (litter saprophytes and soil saprophytes). Changes in fungal community composition explained 45.0% variation of different nitrogen fractions. Some key genera (e.g., Saitozyma and Mortierella) play a key role in promoting soil nitrogen transformation and accumulation. Therefore, the conversion of pure C. lanceolata plantation to two-layered C. lanceolata + P. bournei plantation was conducive to improving soil nitrogen and phosphorus availability. Bacteria and fungi played important roles in the transformation process of soil nitrogen and phosphorus forms, with greater contribution of soil fungi.

Alterations in microbiota of patients with COVID-19: implications for therapeutic interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 million deaths. Patients with coronavirus disease (COVID-19) may suffer from diarrhea, sleep disorders, depression, and even cognitive impairment, which is associated with long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients with COVID-19 have alterations in microbiota and their metabolites, particularly in the gut, which may be involved in the regulation of immune responses. Consumption of probiotics may alleviate the discomfort caused by inflammation and oxidative stress. However, the pathophysiological process underlying the alleviation of COVID-19-related symptoms and complications by targeting the microbiota remains unclear. In the current study, we summarize the latest research and evidence on the COVID-19 pandemic, together with symptoms of SARS-CoV-2 and vaccine use, with a focus on the relationship between microbiota alterations and COVID-19-related symptoms and vaccine use. This work provides evidence that probiotic-based interventions may improve COVID-19 symptoms by regulating gut microbiota and systemic immunity. Probiotics may also be used as adjuvants to improve vaccine efficacy.

Nrf-2/ROS/NF-κB pathway is modulated by cynarin in human mesenchymal stem cells in vitro from ankylosing spondylitis.

Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti-inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS-MSCs, we found that the expression levels of p-NF-κB, IL-6, IL-1ß, and TNF-α were higher and IκB-α, Nrf-2, and HO-1 were lower compared with healthy control (HC)-MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1-Nrf-2 and p65-IκB-α were predicted. The mRNA and protein expression of p-NF-κB, IL-6, IL-1ß, and TNF-α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB-α, Nrf-2, and HO-1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS-MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf-2/ROS/NF-κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS.

Preoperative supine pelvic incidence predicts standing pelvic incidence following S2AI fixation in patients with adult spinal deformity: a prospective study.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the PI change in different postures and before and after S2­alar­iliac (S2AI) screw fixation, and to investigate whether pre-op supine PI could predict post-op standing PI. Previous studies have reported PI may change with various positions. Some authors postulated that the unexpected PI change in ASD patients could be due to sacroiliac joint laxity, S2-alar-iliac (S2AI) screw placement, or aggressive sagittal cantilever technique. However, there was a lack of investigation on how to predict post-op standing PI when making surgical strategy. METHODS: A prospective case series of ASD patients undergoing surgical correction with S2AI screw placement was conducted. Full-spine X-ray films were obtained at pre-op standing, pre-op supine, pre-op prone, as well as post-op standing postures. Pelvic parameters were measured. Spearman correlation analysis was used to determine relationships between each parameter. RESULTS: A total of 83 patients (22 males, 61females) with a mean age of 58.4 ± 9.5 years were included in this study. Pre-op standing PI was significantly lower than post-op standing PI (p = 0.004). Pre-op prone PI was significantly lower than post-op standing PI (p = 0.001). By contrast, no significant difference was observed between pre-op supine and post-op standing PI (p = 0.359) with a mean absolute difference of 2.2° ± 1.9°. Correlation analysis showed supine PI was significantly correlated with post-op standing PI (r = 0.951, p < 0.001). CONCLUSION: This study revealed the PI changed after S2AI screw fixation. The pre-op supine PI can predict post-op standing PI precisely, which facilitates to provide correction surgery strategy with a good reference for ideal sagittal alignment postoperatively.

Rapid anaerobic culture and reaction kinetic study of anammox bacteria on microfluidic chip.

Anammox bacteria are being increasingly investigated as part of an emerging nitrogen removal technology. However, due to the difficulty in culturing, current understanding of their behavior is limited. In this study, anaerobic microfluidic chips were used to study anammox bacteria, showing great advantages over reactors. On-chip fluorescence in situ hybridization (FISH) showed the relative abundance of free form anammox bacteria increased by 56.1 % after one week's culture, an increase that is three times higher than that of bioreactor (17.1 %). For granular form cultures, the nitrogen removal load reached 2.34 âˆ¼ 2.51 kg-N/(m3·d), which was also substantially higher than the bioreactor (∼1.22 kg-N/(m3·d)). Furthermore, studying the kinetics of nitrite inhibition of granular sludge with different particle sizes (100-900 µm) showed that the maximum ammonia load and the nitrite semi-saturation coefficient noticeably decreased for smaller particle sizes. These results illustrate the usefulness of the microfluidic method for in-depth understanding anammox process and its implementation.

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis.

OBJECTIVE: Low bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover. METHODS: A total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X-ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score < -1, and the normal (NOR) group if the Z score ≥ -1 SD compared to the healthy control. For the 16S rRNA sequencing, the raw reads were filtered to remove low-quality reads, and operational taxonomic units were identified with the Uparse program. Weighted UniFrac distance matrix for the beta-diversity metrics and principal coordinate analysis (PCoA) was performed, and the statistical comparisons were made with permutational multivariate analysis of variance (PERMANOVA) and analysis of similarity (ANONISM). Linear discriminant analysis effect size (LEfSe) was used to identify the enriched species in two groups. The "Random forest" was applied to determine the optimal biomarker for OPN according to the mean decrease in Gini value. The metabolic function was predicted by the Tax4Fun analysis. The Pearson correlation coefficient was used to evaluate the associations between GM species, bone turnover markers, and BMD. RESULTS: The serum ß-CTX was increased in the OPN group (n = 67) compared to the NOR group (n = 59). Patients in OPN groups showed significantly decreased α diversity indicated by the Shannon index. Principal coordinate analysis (PCoA) analysis showed significant clustering of GM between OPN and NOR groups. At genus level, the Escherichia-Shigella and Faecalibacterium were significantly enriched in the OPN group compared to that in the NOR group (p < 0.05), whereas the abundance of Prevotella was significantly decreased (p = 0.0012). The relative abundance of Megamonas and Prevotella was positively correlated with the femur BMD. The abundance of Escherichia-Shigella was negatively correlated with femur BMD and positively correlated with serum ß-CTX levels. Functional analysis revealed significant differences in starch and sucrose metabolism, pyruvate and cysteine, and methionine metabolism between NOR and OPN groups. CONCLUSION: The alterations of GM in AIS patients are correlated with osteopenia. The association between enriched species, BMD, and bone turnover markers provides novel diagnostic and therapeutic targets for the clinical management of AIS.

Distinguishing schizophrenia and bipolar disorder through a Multiclass Classification model based on multimodal neuroimaging data.

This study aimed to identify neural biomarkers for schizophrenia (SZ) and bipolar disorder (BP) by analyzing multimodal neuroimaging. Utilizing data from structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), multiclass classification models were created for SZ, BP, and healthy controls (HC). A total of 113 participants (BP: 31, SZ: 39, and HC: 43) were recruited under strict enrollment control, from which 272, 200, and 1875 features were extracted from sMRI, DTI, and rs-fMRI data, respectively. A support vector machine (SVM) with recursive feature elimination (RFE) was employed to build the models using a one-against-one approach and leave-one-out cross-validation, achieving a classification accuracy of 70.8%. The most discriminative features were primarily from rs-fMRI, along with significant findings in sMRI and DTI. Key biomarkers identified included the increased thickness of the left cuneus cortex and decreased regional functional connectivity strength (rFCS) in the left supramarginal gyrus as shared indicators for BP and SZ. Additionally, decreased fractional anisotropy in the left superior fronto-occipital fasciculus was suggested as specific to BP, while decreased rFCS in the left inferior parietal area might serve as a specific biomarker for SZ. These findings underscore the potential of multimodal neuroimaging in distinguishing between BP and SZ and contribute to the understanding of their neural underpinnings.

Potential impairment of spinal cord around the apical vertebral level in hyperkyphotic patients: findings from diffusion tensor imaging.

PURPOSE: To evaluate the neuronal metrics/microstructure of the spinal cord around apical region in patients with hyperkyphosis using diffusion tensor imaging (DTI). METHODS: Thirty-seven patients with hyperkyphosis aged 45.5 ± 19.6 years old who underwent 3.0 T magnetic resonance imaging (MRI) examination with DTI sequence were prospectively enrolled from July 2022 to July 2023. Patients were divided into three groups according to spinal cord/ cerebrospinal fluid (CSF) architecture on sagittal-T2 MRI of the thoracic apex (the axial spinal cord classification): Group A-circular cord with visible CSF, Group B-circular cord without visible CSF at apical dorsal, and Group C-spinal cord deformed without intervening CSF. The fractional anisotropy (FA) values acquired from DTI were compared among different groups. Correlations between DTI parameters and global kyphosis (GK)/sagittal deformity angular ratio (sagittal DAR) were evaluated using Pearson correlation coefficients. RESULTS: In all patients, FA values were significantly lower at apical level as compared with those at one level above or below the apex (0.548 ± 0.070 vs. 0.627 ± 0.056 versus 0.624 ± 0.039, P < 0.001). At the apical level, FA values were significantly lower in Group C than those in Group B (0.501 ± 0.052 vs. 0.598 ± 0.061, P < 0.001) and Group A (0.501 ± 0.052 vs. 0.597 ± 0.019, P < 0.001). Moreover, FA values were significantly lower in symptomatic group than those in non-symptomatic group (0.498 ± 0.049 v. 0.578 ± 0.065, P < 0.001). Pearson correlation analysis showed that GK (r2 = 0.3945, P < 0.001) and sagittal DAR (r2 = 0.3079, P < 0.001) were significantly correlation with FA values at apical level. CONCLUSION: In patients with hyperkyphosis, the FA of spinal cord at apical level was associated with the neuronal metrics/microstructure of the spinal cord. Furthermore, the DTI parameter of FA at apical level was associated with GK and sagittal DAR.

Label-free and highly-sensitive detection of calcium ions using a silicon-on-sapphire light-addressable potentiometric sensor.

BACKGROUND: Ionic calcium (Ca2+) plays a crucial role in maintaining normal physiological and biochemical functions within the human body. Detecting the concentration of Ca2+ is of utmost significance for various purposes, including disease screening, cellular metabolism research, and evaluating drug effectiveness. However, current detection approaches such as fluorescence and colorimetry face limitations due to complex labeling techniques and the inability to track changes in Ca2+ concentration. In recent years, extensive research has been conducted in this field to explore label-free and efficient approaches. RESULTS: In this study, a novel light-addressed potentiometric sensor (LAPS) using silicon-on-sapphire technology, has been successfully developed for Ca2+ sensing. The Ca2+-sensitive LAPS achieved a wide-range detection of Ca2+, ranging from 10-2 M to 10-7 M, with an impressive detection limit of 100 nM. These advancements are attributed to the ultra-thin silicon layer, silicon dioxide layer, and solid-state silicon rubber sensitive membrane around 6 µm. Furthermore, the sensor demonstrated the ability to dynamically monitor fluctuations in Ca2+ concentration ranging from 10-9 M to 10-2 M within a solution. Its remarkable selectivity, specificity, and long-term stability have facilitated its successful application in the detection of Ca2+ in human serum and urine. SIGNIFICANCE AND NOVELTY: This work presents a Ca2+-sensitive sensor that combines a low detection limit and a wide detection range. The development represents the emergence of a label-free and rapid Ca2+ detection tool with immense prospects in home-based health monitoring, community disease screening, as well as cellular metabolism, and drug screening evaluations.

Syringo-Subarachnoid Shunt with Tube Versus T-Tube via the Dorsal Root Entry Zone Approach for Eccentric Syringomyelia.

OBJECTIVE: This study compared the clinical therapeutic efficacy of syringo-subarachnoid shunt placement with direct tube and T-tube via the dorsal root entry zone (DREZ) approach for treatment of eccentric syringomyelia. METHODS: A retrospective study was performed of 41 patients with idiopathic or secondary eccentric syringomyelia from November 2011 to December 2022. Syringo-subarachnoid shunt placement with direct tube or T-tube via the DREZ approach was performed. The modified Japanese Orthopaedic Association low back pain scale was used to investigate the severity of clinical symptoms. Magnetic resonance imaging was used to investigate therapeutic efficacy（reduction of the cavity volume by >10% was considered an improvement and 50% was considered a significant improvement). RESULTS: Incision length of the spinal cortex in the direct tube group was shorter than in the T-tube group (3.10 ± 0.28 cm vs. 5.03 ± 0.19 cm), with a significant difference between the 2 groups (t = -52.56, P < 0.001). Modified Japanese Orthopaedic Association score 3 months postoperatively was significantly better than the preoperative score in both the direct tube group（t = 40.954, P < 0.001） and the T-tube group（t = 24.769, P < 0.001）. Statistical comparison revealed there was no difference in imaging improvement between the direct tube group and T-tube group 3 months (χ2 = 0.20, P = 0.655) and 12 months (χ2 = 0.21, P = 0.647) postoperatively. CONCLUSIONS: Syringo-subarachnoid shunt placement with direct tube via the DREZ approach for treatment of eccentric syringomyelia is safer than with T-tube via the DREZ approach due to smaller incision length and less of a space-occupying effect with same therapeutic efficacy.

Free-hand technique of C7 pedicle screw insertion using a simply defined entry point without fluoroscopic guidance for cervical spondylotic myelopathy patients with C3 to C6 instrumented by lateral mass screws: a retrospective cohort study.

BACKGROUND: Nowadays, both lateral mass screw (LMS) and pedicle screw were effective instrumentation for posterior stabilization of cervical spine. This study aims to evaluate the feasibility of a new free-hand technique of C7 pedicle screw insertion without fluoroscopic guidance for cervical spondylotic myelopathy (CSM) patients with C3 to C6 instrumented by lateral mass screws. METHODS: A total of 53 CSM patients underwent lateral mass screws instrumentation at C3 to C6 levels and pedicle screw instrumentation at C7 level were included. The preoperative 3-dimenional computed tomography (CT) reconstruction images of cervical spine were used to determine 2 different C7 pedicle screw trajectories. Trajectory A passed through the axis of the C7 pedicle while trajectory B selected the midpoint of the base of C7 superior facet as the entry point. All these 53 patients had the C7 pedicle screw inserted through trajectory B by free-hand without fluoroscopic guidance and the postoperative CT images were obtained to evaluate the accuracy of C7 pedicle screw insertion. RESULTS: Trajectory B had smaller transverse angle, smaller screw length, and smaller screw width but both similar sagittal angle and similar pedicle height when compared with trajectory A. A total of 106 pedicle screws were inserted at C7 through trajectory B and only 8 screws were displaced with the accuracy of screw placement as high as 92.5%. CONCLUSION: In CSM patients with C3 to C6 instrumented by LMS, using trajectory B for C7 pedicle screw insertion is easy to both identify the entry point and facilitate the rod insertion.

[Binocular loupe assisted mini-lateral and medial incisions in lateral position for release of elbow stiffness].

Objective: To analyze the effectiveness of binocular loupe assisted mini-lateral and medial incisions in lateral position for the release of elbow stiffness. Methods: The clinical data of 16 patients with elbow stiffness treated with binocular loupe assisted mini-internal and external incisions in lateral position release between January 2021 and December 2022 were retrospectively analyzed. There were 9 males and 7 females, aged from 19 to 57 years, with a median age of 33.5 years. Etiologies included olecranon fracture in 6 cases, elbow dislocation in 4 cases, medial epicondyle fracture in 2 cases, radial head fracture in 4 cases, terrible triad of elbow joint in 2 cases, supracondylar fracture of humerus in 1 case, coronoid process fracture of ulna in 1 case, and humerus fracture in 1 case, with 5 cases presenting a combination of two etiologies. The duration of symptoms ranged from 5 to 60 months, with a median of 8 months. Preoperatively, 12 cases had concomitant ulnar nerve numbness, and 6 cases exhibited ectopic ossification. The preoperative range of motion for elbow flexion and extension was (58.63±22.30)°, the visual analogue scale (VAS) score was 4.3±1.6, and the Mayo score was 71.9±7.5. Incision lengths for both lateral and medial approaches were recorded, as well as the occurrence of complications. Clinical outcomes were evaluated using Mayo scores, VAS scores, and elbow range of motion both preoperatively and postoperatively. Results: The lateral incision lengths for all patients ranged from 3.0 to 4.8 cm, with an average of 4.1 cm. The medial incision lengths ranged from 2.4 to 4.2 cm, with an average of 3.0 cm. The follow-up duration ranged from 6 to 19 months and a mean of 9.2 months. At last follow-up, 1 patient reported moderate elbow joint pain, and 3 cases exhibited residual mild ulnar nerve numbness. The other patients had no complications such as new heterotopic ossification and ulnar nerve paralysis, which hindered the movement of elbow joint. At last follow-up, the elbow range of motion was (130.44±9.75)°, the VAS score was 1.1±1.0, and the Mayo score was 99.1±3.8, which significantly improved when compared to the preoperative ones ( t=-12.418, P<0.001; t=6.419, P<0.001; t=-13.330, P<0.001). Conclusion: The binocular loupe assisted mini-lateral and medial incisions in lateral position integrated the advantages of traditional open and arthroscopic technique, which demonstrated satisfying safety and effectivity for the release of elbow contracture, but it is not indicated for patients with posterior medial heterolateral heterotopic ossification.

Multicargo-loaded inverse opal gelatin hydrogel microparticles for promoting bacteria-infected wound healing.

Nowadays, many strategies have been developed to design biomaterials to accelerate bacteria-infected wound healing. Here, we presented a new type of multicargo-loaded inverse opal hydrogel microparticle (IOHM) for regulating oxidative stress, antibiosis, and angiogenesis of the bacteria-infected wound. The methacrylate acylated gelatin (GelMA)-based inverse opal hydrogel microparticles (IOHMs) were obtained by using the colloidal crystal microparticles as templates, and fullerol, silver nanoparticles (Ag NPs), and vascular endothelial growth factor (VEGF) were loaded in IOHMs. The developed multicargo-loaded IOHMs displayed good size distribution and biocompatibility, and when they were applied in cell culture, bacteria culture, and animal experiments, they exhibited excellent anti-oxidative stress properties, antibacterial properties, and angiogenesis. These characteristics of the developed multicargo-loaded IOHMs make them ideal for bacteria-infected wound healing.

Assessing Neurologic Complications in Thoracic Three-Column Osteotomy: A Clinical Application of a Novel MRI-Based Classification Approach.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To investigate the occurrence of neurologic complications in patients undergoing thoracic three-column osteotomy (3CO) utilizing an MRI-based classification that assesses spinal cord shape and the presence of cerebrospinal fluid (CSF) at the curve apex, and evaluate its prognostic capacity for postoperative neurologic deficits. SUMMARY OF BACKGROUND DATA: Recent advancements in correction techniques have improved outcomes for severe spinal deformity patients undergoing 3CO. A novel MRI-based spinal cord classification system was introduced, but its validation and association with postoperative complications remain unexplored. MATERIALS AND METHODS: Between September 2012 and September 2018, a retrospective analysis was conducted on 158 adult patients with spinal deformities undergoing 3CO. Radiographic parameters were measured. T2-weighted axial MRI was employed to describe spinal cord morphology at the apex. Intraoperative neurophysiologic monitoring (INOM) alerts were recorded, and preoperative and postoperative neurologic functions were assessed using the Frankel score. Categorical data were compared using the Chi-Square or Fisher's exact test. The paired t-test was utilized to assess the mean difference between pre- and postoperative measurements, while the one-way ANOVA and independent t-test were employed for comparative analyses among the different spinal cord types. RESULTS: Patients were categorized into three groups: type 1, type 2, and type 3, consisting of 12, 85, and 61 patients. Patients with type 3 morphology exhibited larger Cobb angles of the main curve (P<.001). This disparity persisted both postoperatively and during follow-up (P<.05). IONM alerts were triggered in 32 patients (20.3%), with a distribution of one case in type 1, six cases in type 2, and 22 cases in type 3 morphologies (P<.001). New neurologic deficits were observed in 15 patients (9.5%), with one, three, and 11 cases in type 1, 2, and 3 morphologies, respectively. CONCLUSIONS: Patients with type 3 morphology exhibited greater spinal deformity severity, higher likelihood of preoperative neurologic deficits, and an elevated risk of postoperative neurologic complications. This underscores the utility of the classification as a tool for predicting postoperative neurologic complications in patients undergoing thoracic 3CO. LEVEL OF EVIDENCE: Level IV.

Validation of Roussouly classification in predicting the occurrence of adjacent segment disease after short-level lumbar fusion surgery.

BACKGROUND: Recent studies demonstrated that restoring sagittal alignment to the original Roussouly type can remarkably reduce complication rates after adult spinal deformity surgery. However, there is still no data proving the benefit of maintaining ideal Roussouly shape in the lumbar degenerative diseases and its association with the development of adjacent segment disease (ASD). Thus, this study was performed to validate the usefulness of Roussouly classification to predict the occurrence of ASD after lumbar fusion surgery. MATERIALS AND METHODS: This study retrospectively reviewed 234 consecutive patients with lumbar degenerative diseases who underwent 1- or 2-level fusion surgery. Demographic and radiographic data were compared between ASD and non-ASD groups. The patients were classified by both "theoretical" [based on pelvic incidence (PI)] and "current" (based on sacral slope) Roussouly types. The patients were defined as "matched" if their "current" shapes matched the "theoretical" types and otherwise as "mismatched". The logistic regression analysis was performed to identify the factors associated with ASD. Finally, clinical data and spinopelvic parameters of "theoretical" and "current" types were compared. RESULTS: With a mean follow-up duration of 70.6 months, evidence of ASD was found in the 68 cases. Postoperatively, ASD group had more "current" shapes classified as type 1 or 2 and fewer as type 3 than the non-ASD group (p < 0.001), but the distribution of "theoretical" types was similar between groups. Moreover, 80.9% (55/68) of patients with ASD were mismatched, while 48.2% (80/166) of patients without ASD were mismatched (p < 0.001). A multivariate analysis identified age [odds ratio (OR) = 1.058)], 2-level fusion (OR = 2.9830), postoperative distal lordosis (DL, OR = 0.949) and mismatched Roussouly type (OR = 4.629) as independent risk factors of ASD. Among the four "theoretical" types, type 2 had the lowest lumbar lordosis, DL, and segmental lordosis. When considering the "current" types, current type 2 was associated with higher rates of 2-level fusion, worse DL, and greater pelvic tilt compared with other current types. CONCLUSIONS: DL loss and mismatched Roussouly type were significant risk factors of ASD. To decrease the incidence of ASD, an appropriate value of DL should be achieved to restore sagittal alignment back to the ideal Roussouly type. LEVEL OF EVIDENCE: Level 4.

Repeated Ketamine Anesthesia during the Neonatal Period Impairs Hippocampal Neurogenesis and Long-Term Neurocognitive Function by Inhibiting Mfn2-Mediated Mitochondrial Fusion in Neural Stem Cells.

The mechanism of ketamine-induced neurotoxicity development remains elusive. Mitochondrial fusion/fission dynamics play a critical role in regulating neurogenesis. Therefore, this study was aimed to evaluate whether mitochondrial dynamics were involved in ketamine-induced impairment of neurogenesis in neonatal rats and long-term synaptic plasticity dysfunction. In the in vivo study, postnatal day 7 (PND-7) rats received intraperitoneal (i.p.) injection of 40 mg/kg ketamine for four consecutive times at 1 h intervals. The present findings revealed that ketamine induced mitochondrial fusion dysfunction in hippocampal neural stem cells (NSCs) by downregulating Mitofusin 2 (Mfn2) expression. In the in vitro study, ketamine treatment at 100 µM for 6 h significantly decreased the Mfn2 expression, and increased ROS generation, decreased mitochondrial membrane potential and ATP levels in cultured hippocampal NSCs. For the interventional study, lentivirus (LV) overexpressing Mfn2 (LV-Mfn2) or control LV vehicle was microinjected into the hippocampal dentate gyrus (DG) 4 days before ketamine administration. Targeted Mfn2 overexpression in the DG region could restore mitochondrial fusion in NSCs and reverse the inhibitory effect of ketamine on NSC proliferation and its faciliatory effect on neuronal differentiation. In addition, synaptic plasticity was evaluated by transmission electron microscopy, Golgi-Cox staining and long-term potentiation (LTP) recordings at 24 h after the end of the behavioral test. Preconditioning with LV-Mfn2 improved long-term cognitive dysfunction after repeated neonatal ketamine exposure by reversing the inhibitory effect of ketamine on synaptic plasticity in the hippocampal DG. The present findings demonstrated that Mfn2-mediated mitochondrial fusion dysfunction plays a critical role in the impairment of long-term neurocognitive function and synaptic plasticity caused by repeated neonatal ketamine exposure by interfering with hippocampal neurogenesis. Thus, Mfn2 might be a novel therapeutic target for the prevention of the developmental neurotoxicity of ketamine.

L4/5 Disc Herniation: Not Unusually Accompanied with L5/S1 Low-Grade Spondylolytic Spondylolisthesis.

OBJECTIVE: Isthmic spondylolisthesis (IS) is distinguished by a congenital defect or acquired fracture of the pars interarticularis. Numerous studies on L5 low-grade IS have been carried out; however, there is a paucity of data regarding the condition of L5 IS concomitant with L4/5 disc herniation. This study aimed to identify the incidence rate and to illustrate the possible risk factors for L4/5 disc herniation in L5 low-grade IS patients. METHODS: A total of 268 consecutive patients diagnosed as L5/S1 low-grade IS between May 2017 and May 2022 were retrospectively enrolled in this study. Depending on the presence of L4/5 disc herniation or not, patients were divided into an L4/5 disc herniation group (L4/5 DH) and an L4/5 non-disc herniation group (L4/5 non-DH). Radiographic parameters were measured, and the ratios of L4-S1 segmental lordosis (SL) to lumbar lordosis (LDI), L4 inferior endplate (IEP) to L5 superior endplate (SEP) (L4 IEP/L5 SEP), and L5 IEP to S1 SEP (L5 IEP/S1 SEP) were compared between groups. The Pfirrmann grade of the L4/5 disc and the L5/S1 disc, and Roussouly classifications of each patient were also recorded. Univariate analysis (including independent-samples t-test and χ2 -test) and multiple logistic regression analysis were performed to analyze the data. RESULTS: There were 40 patients (14.9%) in the L4/5 DH group. The Roussouly classification differed significantly between groups. As demonstrated by the Pfirrmann grade, the L4/5 DH group showed more advanced disc degeneration at L4/5 than the L4/5 non-DH group. In contrast to the L4/5 non-DH group, the L4/5 DH group had a significantly larger L4 IEP, L4 IEP/L5 SEP, S1 SEP, and LDI while smaller L4/5 disc angle, L4/5 disc height, slip percentage, lumbar lordosis, and sacral slope. Multivariate logistic regression analysis revealed that higher L4/5 disc Pfirrmann grade (p = 0.004), decreased L4/5 disc height (p < 0.001), and lower L5 slip percentage (p = 0.022) were significantly associated with the occurrence of L4/5 DH. CONCLUSIONS: L4/5 disc herniation is not unusually accompanied by L5/S1 low-grade IS. Advanced L4/5 disc degeneration, decreased L4/5 disc height, and lower L5 slip percentage might be significantly associated with L4/5 disc herniation.