Rare variant association analyses reveal the significant contribution of carbohydrate metabolic disturbance in severe adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), the predominant genetic-influenced scoliosis, results in spinal deformities without vertebral malformations. However, the molecular aetiology of AIS remains unclear. METHODS: Using genome/exome sequencing, we studied 368 patients with severe AIS (Cobb angle >40°) and 3794 controls from a Han Chinese cohort. We performed gene-based and pathway-based weighted rare variant association tests to assess the mutational burden of genes and established biological pathways. Differential expression analysis of muscle tissues from 14 patients with AIS and 15 controls was served for validation. RESULTS: SLC16A8, a lactate transporter linked to retinal glucose metabolism, was identified as a novel severe AIS-associated gene (p=3.08E-06, false discovery rate=0.009). Most AIS cases with deleterious SLC16A8 variants demonstrated early onset high myopia preceding scoliosis. Pathway-based burden test also revealed a significant enrichment in multiple carbohydrate metabolism pathways, especially galactose metabolism. Patients with deleterious variants in these genes demonstrated a significantly larger spinal curve. Genes related to catabolic processes and nutrient response showed divergent expression between AIS cases and controls, reinforcing our genomic findings. CONCLUSION: This study uncovers the pivotal role of genetic variants in carbohydrate metabolism in the development of AIS, unveiling new insights into its aetiology and potential treatment.

A Novel growth guidance system for early onset scoliosis: a preliminary in vitro study.

PURPOSE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. METHOD: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001). CONCLUSION: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Can the Sterilization Protocol Be Improved to Enhance the Healing of Allograft Tendons? An In Vivo Study in Rabbit Tendons.

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm2 versus 256 ± 43 /mm2, mean difference 188 /mm2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m2 versus 8 ± 4 kJ/m2, mean difference 8 kJ/m2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.

Is it necessary to extend fusion to L4 when correcting pediatric L5-S1 spondylolisthesis?

OBJECTIVE: The objective of this study was to investigate whether extending fusion to L4 is imperative in the surgical treatment of pediatric L5-S1 spondylolisthesis. METHODS: This retrospective analysis encompassed 68 pediatric cases of dysplastic L5-S1 spondylolisthesis who underwent posterior lumbar interbody fusion surgery at two hospitals. Patients were categorized into two groups based on the upper instrumented vertebra (group L4 and group L5). Data were collected from medical records and radiological images obtained preoperatively and at last follow-up. Radiographic parameters including slip percentage (SP), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), Spinal Deformity Study Group dysplastic lumbosacral angle (SDSG-LSA), pelvic tilt (PT), Dubousset's lumbosacral angle (Dub-LSA), sacral slope (SS), and severity index (SI) were measured. Surgery-related data and complication data were also collected. The incidence rates of complications were compared, including those of neurological deficit, adjacent-segment instability (ASI), and other complications. ASI was defined as progression of slippage > 3 mm or posterior opening > 5° in the adjacent segment. Clinical outcomes were assessed with the numeric rating scale (NRS) and the Oswestry Disability Index (ODI) scores. The follow-up period for all patients lasted a minimum of 2 years. RESULTS: Among all 68 patients, group L4 consisted of 15 patients and group L5 comprised 53 patients. The patients included in both groups had comparable baseline demographic characteristics and radiographic parameters. Postoperative SP and SDSG-LSA were significantly lower in group L5 (p < 0.05). No other postoperative radiographic differences were observed between groups. One patient in group L4 and 3 patients in group L5 experienced transient neurological deficits (p > 0.05). There were 13 cases of ASI in group L5 compared with none in group L4 (24.5% vs 0%, p > 0.05). Of the 13 patients with ASI, 4 underwent revision surgery due to L4-5 level instability and clinical symptoms. The remaining individuals exhibited no symptoms, and regular annual follow-up assessments are being conducted for all patients. The NRS and ODI scores at final follow-up did not exhibit any significant differences between the two groups. CONCLUSIONS: Fusion to L5 could achieve comparable satisfactory results to fixation to L4, albeit with increased likelihood of ASI. Extension of fusion to L4 may not be necessary for most patients with pediatric L5-S1 spondylolisthesis.

Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine.

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Optimal time window for initiating cefuroxime surgical antimicrobial prophylaxis in spinal fusion surgery: a nested case-control study.

BACKGROUND CONTEXT: Surgical site infections (SSI) are one of the common complications following spinal fusion surgery. Unfortunately, several studies had shown conflicting results regarding optimal timing of surgical antimicrobial prophylaxis (SAP) administration. Due to limitations in population homogeneity and sample size, these studies have not provided significant statistical correlations or clear practical recommendations. PURPOSE: The purpose of the study was to investigate the impact of timing of cefuroxime SAP on the risk of SSI in patients undergoing spinal fusion surgery, and to determine the optimal timing of administration. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: This was a retrospective nested case-control study. All consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021 formed a retrospective cohort. For each SSI case, 2 controls free of SSI at the time of the index date of their corresponding case were selected, matched by age, sex, and calendar year. Electronic record and radiographic data were reviewed retrospectively in electronic database. SAP related data included timing of administration, preoperative dose, intraoperative second dose, and postoperative use. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Subsequently, subgroup analyses were conducted to assess the robustness of the statistical associations. RESULTS: According to the pre-planned statistical scheme and matching factors, we matched 236 controls for these SSI cases, and the subsequent statistical analysis was performed on these 354 patients. After adjusting for confounding factors, the results indicated that the risk of SSI was 70% higher in the group receiving SAP 31 to 60 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=1.732, 95%CI 1.031-2.910, p=.038). Additionally, the risk of SSI was 150% higher in the group receiving SAP 61 to 120 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=2.532, 95%CI 1.250-5.128, p=.010). In subgroup analysis, this statistical trend persisted for both deformity surgeries and different SSI classifications. CONCLUSION: Administering cefuroxime SAP within 30 minutes before skin incision significantly reduces the risk of SSI, whether they are deep or superficial, in spinal fusion surgery. This pattern remains consistent among spinal deformity patients.

Early mobilization can reduce the incidence of surgical site infections in patients undergoing spinal fusion surgery: A nested case-control study.

BACKGROUND: To examine the influence of early mobilization on the risk of surgical site infections (SSI) in patients undergoing spinal fusion surgery. METHODS: The retrospective cohort consisted of all consecutive patients who underwent spinal fusion surgery at our institution. For each case of SSI, 2 control patients without SSI at the corresponding index date were selected. Mobilization was predefined as "delayed" if it occurred more than 36 hours postoperatively. To account for potential confounding variables, we performed further adjustments using conditional logistic regression models. Subgroup analyses were conducted to evaluate the robustness of the statistical associations. RESULTS: Following the predefined statistical protocol and matching criteria, we matched 236 control cases to the SSI cases. Upon adjustment for confounding factors, our findings revealed that the risk of SSI was 120% higher in the group beginning mobilization more than 36 hours after surgery compared to the group beginning mobilization within 36 hours postoperatively (odds ratio = 2.206, 95% confidence interval 1.169-4.166, P = .015). In subgroup analyses, this statistical trend remained consistent. CONCLUSIONS: Early mobilization within 36 hours following spinal fusion surgery significantly reduces the risk of SSI. This pattern of reduced risk remains consistent among patients with degenerative diseases or spinal deformities.

Effect Modification of COVID-19 Symptoms on the Association Between Timing of Surgery and Postoperative Complications in Pediatric Spinal Deformity: A Prospective Cohort Study.

OBJECTIVE: The purpose of this study was to explore the optimal timing and associated risks of pediatric spinal deformity surgery during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: All consecutive surgical cases for spinal deformity between September 2022 and May 2023 were included. The population was divided into several categories according to the time from diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to the day of surgery. Postoperative complications were analyzed using logistic regression, and we simultaneously showed the results from the crude model, minimally adjusted model, and fully adjusted model. RESULTS: A total of 81 consecutive patients were enrolled. In the fully adjusted model, compared with pre-COVID-19 patients, peri-COVID-19 patients had a 4.5-fold increased risk of postoperative complications (odds ratio = 5.5, 95% confidence interval 1.1-27.2, P = 0.037), early post-COVID-19 patients had a 2.3-fold increased risk (odds ratio= 3.3, 95% confidence interval 0.7-16.1, P = 0.133), and late post-COVID-19 patients were at essentially equal risk. In asymptomatic population, early post-COVID-19 patients and late post-COVID-19 patients appeared to be at equal risk compared with pre-COVID-19 patients. For patients with persistent symptoms, is necessary to wait at least 8 weeks or even longer after SARS-CoV-2 infection. Interaction tests demonstrated that the effect of the timing of surgery on postoperative complications significantly differed in populations with different symptoms. CONCLUSIONS: Surgery for pediatric spinal deformity should be postponed until 8 weeks after SARS-CoV-2 infection in cases with COVID-19-related symptoms within 2 weeks prior to surgery; whereas, for those who are asymptomatic within 2 weeks prior to surgery, an interval of 4 weeks seemed to be sufficient.

Dual Growing Rods and the Apical Control Technique for Treating Congenital Early-Onset Scoliosis: Lessons Learned.

BACKGROUND: Congenital early-onset scoliosis (CEOS) is characterized by a spectrum of vertebral anomalies, including formation failures and segmentation failures at the apex segment, which makes CEOS different from other etiologies of early-onset scoliosis. To date, studies on patients who have graduated from CEOS treatment using traditional dual growing rods (TDGR) have been scarce, and the preliminary results of TDGR with or without the apical control technique (ACT) have varied. We therefore compared the final outcomes of patients with CEOS who graduated from TDGR with or without the ACT. METHODS: A retrospective study of patients with CEOS who had graduated from TDGR treatment performed from 2007 to 2020 was conducted. Graduation included final fusion or observation after reaching skeletal maturity. Patients were divided into the ACT-TDGR group (apical vertebrectomy and/or hemivertebrectomy with short fusion and TDGR) and the TDGR-only group. Demographic characteristics, radiographic data, patient-reported clinical outcomes, pulmonary function, and complications were analyzed. RESULTS: A total of 41 patients with CEOS were enrolled: 13 in the ACT-TDGR group and 28 in the TDGR-only group. The lengthening intervals were longer in the ACT-TDGR group (mean [and standard deviation], 1.26 ± 0.66 years) than in the TDGR-only group (0.80 ± 0.27 years). The preoperative main curve was larger in the ACT-TDGR group (80.53° ± 19.50°) than in the TDGR-only group (64.11° ± 17.50°). The residual curve was comparable between groups (26.31° ± 12.82° in the ACT-TDGR group compared with 27.76° ± 15.0° in the TDGR group) at the latest follow-up. The changes in apical vertebral rotation and thoracic rotation were significantly larger in the ACT-TDGR group. Patients had comparable T1-12 and T1-S1 heights, pulmonary function, and 22-item Scoliosis Research Society (SRS-22) scores at the latest follow-up. The mean number of mechanical-related complications per patient was lower in the ACT-TDGR group (0.77 ± 0.73) than in the TDGR-only group (1.54 ± 1.43). Seventeen patients underwent final fusion. CONCLUSIONS: In this small-scale study, we observed that both ACT-TDGR and TDGR-only could correct the deformity while allowing for spinal growth in patients with CEOS. ACT-TDGR yielded better correction in severe cases and did not have a deleterious effect on spinal height. A large number of cases will be needed to validate the clinical value of the ACT. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Determinants of Diarrhea Among Children Aged 1 to 6 Years in Flood-Affected Areas of Pakistan: A Cross-Sectional Study.

Frequent floods can contribute to the spread of various diseases and complications, some of which may result in diarrhea, especially among children. The current study aimed to find the determinants of diarrhea among children aged 1-6 years in flood-affected areas in Khyber Pakhtunkhwa, Pakistan. A cross-sectional study was conducted in flood-affected districts. Data regarding sociodemographic information related to diarrhea and anthropometric data were collected through a validated questionnaire. Logistic regression was used to find the determinants of diarrhea. In the presence of diarrhea, the prevalences found of stunting, wasting, and being underweight were 75.2%, 76.5%, and 74.1%, respectively, which is higher than those in children without diarrhea (stunting, 24.8%; wasting, 23.5%; and being underweight, 25.9%). In bivariate regression, children aged 2-4 years (odds ratio [OR] = 1.65, P < 0.05), large family size (OR = 7.46, P < 0.01), low income (OR = 2.55, < 0.001), bathing in ponds (OR = 3.05, P < 0.05), drinking of untreated water (OR = 3, P < 0.05), flooding (OR = 1.8, P < 0.05), children living in mud houses (OR = 1.5, P < 0.05), and usage of utensils without lids (OR = 1.96, P < 0.001) were significantly associated with occurrence of diarrhea. In multivariate regression, the identified risk factors (P < 0.05) for diarrhea in flood-affected areas included illiterate mothers, flooding, large family size, households without livestock, poor water quality, untreated water, and lack of toilet facilities. In conclusion, addressing the determinants of diarrhea identified in this study is crucial for mitigating the impact of frequent floods on children in flood-affected areas. Moreover, the higher prevalence of malnutrition underscores the urgent need for comprehensive strategies and proper water, sanitation, and hygiene programs to reduce the occurrence and determinants of diarrhea.

Outcomes of Ponte osteotomy combined with posterior lumbar interbody fusion for reconstruction of coronal and sagittal balance in degenerative scoliosis.

PURPOSE: The purpose of the study was to evaluate the clinical efficacy and safety of using Ponte osteotomy combined with posterior lumbar interbody fusion in the treatment of patients with degenerative scoliosis. METHOD: The medical records and imaging data of degenerative scoliosis patients in our department from 2013 to 2022 were retrospectively collected. A total of 47 patients were included, including 16 male patients and 31 female patients. The mean follow-up was 47.8 months. Whole spine X-rays in the standing position were performed on all patients preoperatively, postoperatively, and at the latest follow-up. The length of hospital stay, complications, operative duration, estimated blood loss, instrumented segment, fused segment, clinical scores, and various radiological indicators were recorded. RESULTS: The coronal vertical axis improved from 3.1 ± 1.9 cm preoperatively to 1.2 ± 1.0 cm postoperatively with an average reduction of 1.9 ± 1.7 cm. The preoperative coronal Cobb angle was 18.1 ± 10.6°, the immediate postoperative Cobb angle was 6.6 ± 3.9°, and the Cobb angle at the last follow-up was 5.8 ± 3.7°. The sagittal vertical axis decreased from 5.6 ± 3.7 cm preoperatively to 2.7 ± 1.9 cm immediately after the operation and was well maintained at the last follow-up (3.1 ± 2.5 cm). Lumbar lordosis increased from 22.2 ± 10.2° preoperatively to 40.4 ± 8.3° postoperatively and 36.0 ± 8.8° at the last follow-up. The ODI score, VAS low back pain score, and VAS leg pain score were also improved to varying degrees. CONCLUSION: Ponte osteotomy combined with posterior lumbar interbody fusion can significantly improve coronal and sagittal plane deformities and postoperative functional scores in patients with adult degenerative scoliosis.

Prognostic Nutritional Index Is a Predictive Marker for Health-Related Quality of Life in Patients with Adult Degenerative Scoliosis.

Our aim was to ascertain whether the prognostic nutritional index (PNI), could predict the health-related quality of life (HRQOL) in patients with adult degenerative scoliosis (ADS) undergoing corrective surgery. We conducted a retrospective analysis of consecutive patients diagnosed with ADS between January 2013 and June 2021. Three nutritional parameters were employed for analysis (PNI, anemia, and hypoalbuminemia). We utilized the Scoliosis Research Society-22 (SRS-22) questionnaire and the Oswestry Disability Index (ODI) questionnaire to assess clinical outcomes. Following the epidemiology guidelines, we presented results from three different models: the crude model, minimally adjusted model, and fully adjusted model. A total of 316 ADS patients were included in the statistical analysis. There was no significant difference in sagittal plane radiographic parameters between the two groups. After adjusting for important confounding factors, PNI was an independent predictor of postoperative HRQOL. Specifically, for each one-unit increase in PNI, there was an approximately 20% higher likelihood of patients achieving a better HRQOL. Furthermore, we did not observe an association between hemoglobin levels or albumin levels and HRQOL. In this study, PNI has been demonstrated to be correlated with the postoperative HRQOL in patients with ADS undergoing corrective surgery.

The role and mechanism of inflammatory response to growing rod implantation in early onset scoliosis.

Growing rod implantation, a surgery treatment for EOS (early onset scoliosis), may cause a kind of chronic inflammation called metalosis and all other implant-related complications because of the metal debris released by the implants as a result of fraction and corrosion. There is no complete explanation of immunologic mechanisms of metalosis up to now. This review demonstrates the researches on metalosis from the clinical issues down to basic immunologic mechanisms. Adverse reactions of metal implants are mainly the formation of NLRP3 (nod-like receptor protein 3) inflammasome, primed by TLR4 (toll-like receptor protein 4), activated by phagocytosis and often accompanied by type Ⅳ hypersensitive reaction. Recent studies found that TNF-α (tumor necrosis factor α) also participates in priming, and activation of inflammasome requires disturbance of lysosome and release of cathepsin B. Ca-074Me and MCC950 are therapeutic interventions worth exploring in aseptic loosening of orthopedic implants.

Traditional Dual Growing Rods With 2 Different Apical Control Techniques in the Treatment of Early-Onset Scoliosis.

OBJECTIVE: Based on traditional dual growing rods (TDGR), apical control techniques (ACTs) were introduced as adjuvant procedures to improve deformity correction at the apex segment in the treatment of early-onset scoliosis (EOS). We aimed to explore whether TDGR+ ACTs have different indications, attain more deformity correction, have negative effects on spinal growth, and have different complications. METHODS: Between 2004 and 2019, a retrospective study of EOS patients treated with TDGR with or without ACTs was conducted and divided into 3 groups: TDGR group; hybrid technique (HT) group: Vertebrectomy/hemivertebrectomy with short fusion and TDGR; ACPS group: apical convex control pedicle screws (ACPS) and TDGR. Demographic, radiographic parameters, clinical outcomes, complications, and revisions were analyzed and compared. RESULTS: Seventy-eight EOS patients were enrolled. The preoperative main curve was the largest in the HT group. ACPS group had the smallest residual curve (19° ± 8.9°) and apical vertebral translation (12.0 ± 9.0 mm) at the latest follow-up, followed by the HT group (30° ± 17.4°, 22.1 ± 13.4 mm) and TDGR group (30° ± 13.2°, 32.8 ± 17.1 mm). ACPS group had the largest T1-12 height and T1-S1 height after index surgery. Complications and revisions in the ACTs groups was lower than the TDGR group. Scoliosis Research Society-22 self-image questionnaire was superior in the ACPS group. CONCLUSION: According to our intermediate results, TDGR+ACTs could improve correction ability of apex deformity. ACTs had little deleterious effects on spinal height during the lengthening procedures, with a lower complication rate than TDGR. TDGR+ACTs might be a supplemental option for suitable EOS patients.

Risk factors for intensive care unit admission following correction surgery for adult spinal deformity.

OBJECTIVE: The literature currently available on the characteristics of patients who require intensive care unit (ICU) admission after correction surgery for adult spinal deformity is lacking; this study aimed to identify risk factors for postoperative ICU admission following correction surgery for adult spinal deformity. METHODS: A retrospective review of patients who underwent primary posterior-based spinal fusion from 2015 to 2023 was performed. According to the ward they returned to, patients were further divided into an ICU group and a non-ICU group. Univariate and multivariate analyses were performed to evaluate preoperative and perioperative parameters to identify independent risk factors for postoperative ICU admission in adult spinal deformity patients. RESULTS: A total of 274 patients were included, including 115 males (41.97%) and 159 females (58.03%). The mean age of the patients was 32.00 ± 11.16 years (19-77 years). Following adjusted analysis, the preoperative and perioperative factors that were independently associated with ICU admission were age, body mass index ≥ 28 kg/m2, neuromuscular spinal deformity, respiratory disease, grade III-IV American Society of Anesthesiologists (ASA) classification, a scoliosis Cobb angle ≥ 90°, a kyphosis Cobb angle ≥ 90°, and ≥ 12 fused segments. Compared with the non-ICU group, the ICU group had a higher incidence of complications, a longer hospital stay, and higher medical costs (P < 0.05). CONCLUSION: This study identified independent risk factors associated with postoperative ICU admission in adult spinal deformity patients; and explored relative measures to decrease or avoid the risk of postoperative ICU admission. Surgeons could use these data to develop and plan appropriate perioperative care processes in advance and provide consultation for family members before surgery.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is an essential transcriptional regulator of cartilage development and homeostasis. In humans, dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic and acampomelic dysplasia, and scoliosis. The mechanism of how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four novel pathogenic variants of SOX9 identified in a large cohort of patients with congenital vertebral malformations. Three of these heterozygous variants are in the HMG and DIM domains, and for the first time, we report a pathogenic variant within the transactivation middle (TAM) domain of SOX9 . Probands with these variants exhibit variable skeletal dysplasia, ranging from isolated vertebral malformation to acampomelic dysplasia. We also generated a Sox9 hypomorphic mutant mouse model bearing a microdeletion within the TAM domain ( Sox9 Asp272del ). We demonstrated that disturbance of the TAM domain with missense mutation or microdeletion results in reduced protein stability but does not affect the transcriptional activity of SOX9. Homozygous Sox9 Asp272del mice exhibited axial skeletal dysplasia including kinked tails, ribcage anomalies, and scoliosis, recapitulating phenotypes observed in human, while heterozygous mutants display a milder phenotype. Analysis of primary chondrocytes and the intervertebral discs in Sox9 Asp272del mutant mice revealed dysregulation of a panel of genes with major contributions of the extracellular matrix, angiogenesis, and ossification-related processes. In summary, our work identified the first pathologic variant of SOX9 within the TAM domain and demonstrated that this variant is associated with reduced SOX9 protein stability. Our finding suggests that reduced SOX9 stability caused by variants in the TAM domain may be responsible for the milder forms of axial skeleton dysplasia in humans.

The incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis.

BACKGROUND: Congenital scoliosis(CS) is associated with multiple organs defect, and cardiac abnormalities have been reported commonly associated with CS. Hemivertebra is caused by the failure of vertebral formation, which is a major constitute of CS. Till now, few studies focus on the incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis. We aimed to analyze the cardiac defect in CS patients with or without hemivertebra, and further explore the incidence of cardiac defect between different types of hemivertebra. METHODS: The ultrasonic cardiography (UCG) results of surgically treated congenital scoliosis (CS) patients between 2015 and 2018 were retrospectively analyzed. Patients were divided into hemivertebra group and non-hemivertebra group according to preoperative CT. Patients with hemivertebra was further divided into sub-group by single/multiple or fully/partially/mixed segmented hemivertebra. Demographic information, radiographic data and cardiac abnormalities were statistically compared between groups. RESULTS: A total of 329 patients were analyzed, including 216 patients with hemivertebra and 113 patients without hemivertebra. UCG results were abnormal in 89 cases (27.1%), including 41 males(12.5%) and 48 females(14.6%). Hemivertebra group had comparable incidence of cardiac abnormalities with non-hemivertebra group (p = 0.517). No significant difference in the incidence of UCG abnormalities between single and multiple hemivertebra group (P = 0.246). Binary logistic regression analysis showed that female sex with multiple hemivertebra was a risk factor for abnormal UCG (P = 0.009, OR = 3.449). Cardiac abnormalities was comparable among fully, partially and mixed segmented hemivertebra group(P = 0.264). In abnormal UCG, 33 patients with hemivertebra had non-valvular abnormalities, and 48.5% (16/33) were septal defects. 28 patients had valvular abnormalities, most of them were mitral valve abnormalities, especially mitral valve redundancy, prolapse and insufficiency(82.1%, 23/28). No significant difference between the incidence of non-valvular and valvular abnormalities in patients with hemivertebra (P = 0.581). CONCLUSIONS: The incidence of abnormal UCG results was approximately 28.2% in CS patients with hemivertebra. Female patients with multiple hemivertebra had a higher risk of UCG abnormalities. Mitral valve abnormalities were the most common abnormality of UCG found in CS patients with hemivertebra. TRIAL REGISTRATION: retrospectively registered.

Ten-year trends in surgical management of 1207 congenital scoliosis.

PURPOSE: To report and analyze development trends in the surgical treatment of congenital scoliosis (CS) in a large CS cohort over a 10-year period. METHODS: We retrospectively searched and extracted medical records of CS inpatients receiving posterior instrumented fusion surgery at our institute from January 2010 to December 2019. We analyzed information on demographics and surgical information, including the surgical approach, number of fused segments, use of osteotomy and titanium cage implantation, length of stay, intraoperative blood loss, and rates of complications and readmission. RESULTS: 1207 CS inpatients were included. In the past decade, the proportion of patients younger than 5 years increased from 15.5 to 26.9%. The average number of fused segments decreased from 9.24 to 7.48, and the proportion of patients treated with short-segment fusion increased from 13.4 to 30.3%. The proportion of patients treated with osteotomy and titanium cage implantation increased from 55.65% and 12.03% to 76.5% and 40.22%. The average length of stay and blood loss decreased from 16.5 days and 816.1 ml to 13.5 days and 501.7 ml. The complication and readmission rates also decreased during these ten years. CONCLUSION: During this ten-year period, the surgical treatment of CS at our institute showed trends toward a younger age at fusion, lower number of fused segments, higher rate of osteotomy and titanium cage implantation, reduced blood loss, shorter length of stay and lower rate complications and readmission. These results suggest performing osteotomy combined with titanium cage implantation at an earlier age can achieve fewer fused segments and complications.