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Purpose: Objectives in scoliosis corrective surgery include restoration of normal sagittal and coronal parameters to achieve patient satisfaction. HRQLs improvements remain limited after corrective surgery. The aim of this study was to evaluate the HRQL subclass variability specific to the sagittal and coronal correction in adult scoliosis surgery. Methods: This multi-centre prospective analysis of consecutive adult spinal deformity (ASD) patients, from five European centres, only included multilevel instrumentation for scoliosis. d-(delta) values for each parameter represented pre to post-operative changes. Parameters included demographics, baseline, 1- and 2-year. HRQL outcomes (Oswestry disability index (ODI), Scoliosis Research Society (SRS)-22 and Short Form (SF36)), sagittal correction including relative spinopelvic alignment (dRSA) and coronal correction including major Cobb (dCobb) angles. Results: A total of 353 patients reached 1-year and 2-year follow up. All HRQL total scores significantly improved postoperatively, including ODI, SRS-22 and SF36. HRQL subclasses which displayed persistent improvements correlated to dRSA included sex-life, self-image, fatigue, vitality, social functioning. The only HRQL subclass improvement that correlated with dCobb was self-image. Conclusion: Adult scoliosis surgery improves overall HRQL, having a minimal effect on each variable. Importantly, greater coronal deformity correction affects only greater self-image scores, whereas with greater sagittal correction there are many greater HRQL sub-class impacts. Correction and restoration of coronal balance is one of the surgical goals in adult scoliosis but the degree to which Cobb angle is corrected, apart from self-image, does not correlate with gains in sub-classes of HRQL. These results need to be taken into account when planning surgery. [ABSTRACT FROM AUTHOR]

Study Design: Multicentric, retrospective analysis of prospectively collected data., Objective: To utilize machine-learning (ML) for clustering and management prediction (conservative vs. operative) in surgically treated adult spine deformity (ASD) patients, and to compare the attainment of the Minimum Clinically Important Difference (MCID) between predicted surgical and conservative patients., Summary of Background Data: Management choice in ASD is complex. ML can identity patient clusters and predicted treatment, but it is unclear whether patients treated according to the prediction also show better clinical outcomes., Methods: ASD patients (2-year follow-up) were divided into groups using k-means clustering. Management choice was predicted among operated patients in each cluster. The MCID for the Oswestry Disability Index (ODI) and the Scoliosis Research Society-22 (SRS-22) was calculated and compared between patients with and without surgical prediction., Results: In Cluster 1 (idiopathic scoliosis, n=675, 150 surgeries), 57% of patients had a conservative prediction. Of these, 52% and 49% achieved MCID for ODI and SRS-22, respectively, compared to 68% and 75% for those with surgical predictions (OR=2 and 3.1, respectively).In Cluster 2 (moderate sagittal imbalance, n=561, 200 surgeries), 12% had a conservative prediction. Of these, 29% and 46% achieved MCID for ODI and SRS-22, respectively, compared to 47% and 56% for those with surgical predictions.In Cluster 3 (significant sagittal imbalance, n=537, 197 surgeries), 17% had a conservative prediction. Of these, 12% and 15% achieved MCID for ODI and SRS-22, respectively, compared to 37% and 45% for those with surgical predictions (OR=4.2 and 4.5, respectively)., Conclusion: Patients with a concordant surgical prediction and management had higher odds of achieving the MCID, indicating a good correlation between prediction and clinical outcomes. In Cluster 3, the low percentage of patients with conservative prediction achieving the MCID suggests that machine learning could well identify patients with poor clinical outcomes., Competing Interests: Conflict of interest: AlBa, DL, SH, CR, AnBu: none; LB Consultant: Spineart, Spinevision; IO: Royalties : Spineart, alphatec, Clariance, Consultant : Medtronic, Depuy, spinevision Research support : Medtronic, Depuy; JP Consultant: Medtronic, Grants: medtronic Depuy; FP: Research support: DePuySpine Synthes / Medtronic / Nuvasive / Orthofix / SpineArt Consultant: Medtronic / Nuvasive; AA: Consultancy: Globus, Zimvie, Research Grant: Depuy, Medtronic Royalty: Zimvie; FK: Depuy Spine Speakers Bureau and Research Grant; YPC: Consultant: Clariance, Stryker, Ceraver, Spinevision, Research Grants: Clariance, Stryker, Medtronic; CY: Consultant, Medtronic. All conflict of interest are not relevant to the present study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Outpatient lumbar decompression surgeries have been successfully performed in France for over twenty years, earning acceptance. However, outpatient instrumented lumbar spine procedures and arthroplasties are less documented. This study aimed to evaluate the feasibility, efficiency, and safety of outpatient lumbar instrumented surgery., Methods: A prospective single-center study involving three experienced surgeons was conducted from September 2020 to September 2021, with a minimum six-month postoperative follow-up. Inclusion criteria comprised patients aged 18 to 75 eligible for same-day discharge, undergoing single-level lumbar spinal fusion or arthroplasty via anterior or posterior Wiltse approach. The primary endpoint was assessing the percentage of successful outpatient discharges (within twelve hours), with secondary endpoints including perioperative/postoperative complications and discharge pain prescriptions in terms of frequency and severity., Results: Forty patients (mean age: 44 years; 16/24 male/female ratio) underwent surgery, including 18 lumbar arthroplasties, twelve ALIF, and ten TLIF procedures. The majority of surgeries were performed at L4-L5 (18 procedures) and L5-S1 levels (22 procedures). 95% (38/40) of patients were successfully discharged within twelve hours, with only two patients discharged the following day. No postoperative hematomas, serious adverse events, or revision surgeries were noted., Conclusion: 95% of patients were discharged successfully within twelve hours following outpatient lumbar fusion surgery, with a 100% patient satisfaction rate. Specific technical solutions were not necessary, and oral pain relief sufficed. Patient selection and education, including early pain management, played crucial roles in complication avoidance. This study underscores the safety of outpatient instrumented lumbar spine procedures, leading to cost reduction and expedited recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cockayne syndrome (CS) is a premature ageing condition characterized by microcephaly, growth failure, and neurodegeneration. It is caused by mutations in ERCC6 or ERCC8 encoding for Cockayne syndrome B (CSB) and A (CSA) proteins, respectively. CSA and CSB have well-characterized roles in transcription-coupled nucleotide excision repair, responsible for removing bulky DNA lesions, including those caused by UV irradiation. Here, we report that CSA dysfunction causes defects in the nuclear envelope (NE) integrity. NE dysfunction is characteristic of progeroid disorders caused by a mutation in NE proteins, such as Hutchinson-Gilford progeria syndrome. However, it has never been reported in Cockayne syndrome. We observed CSA dysfunction affected LEMD2 incorporation at the NE and increased actin stress fibers that contributed to enhanced mechanical stress to the NE. Altogether, these led to NE abnormalities associated with the activation of the cGAS/STING pathway. Targeting the linker of the nucleoskeleton and cytoskeleton complex was sufficient to rescue these phenotypes. This work reveals NE dysfunction in a progeroid syndrome caused by mutations in a DNA damage repair protein, reinforcing the connection between NE deregulation and ageing., (© 2024 Yang et al.)

Study Design: Retrospective analysis of prospectively collected data., Objective: To identify the best definition of primary anteverted pelvis in the setting of adult spine deformity (ASD), and to investigate whether this is a pathologic setting that requires surgical correction., Summary of Background Data: While pelvic retroversion has been thoroughly investigated, pelvic anteversion (AP) is a far lesser discussed topic. Four different AP definitions have been proposed, and AP has been described as a normal or pathologic entity by different authors., Materials and Methods: All patients consulting for ASD at the five participating sites were included. First, the four definitions of AP were compared with descriptive statistics (anatomic method-Pelvic Tilt <0°; Relative Pelvic Version method-RPV >5°; Roussouly method-Pelvic Incidence (PI)<50° and Sacral Slope (SS)>35°); low PT method-PT/PI <25th percentile). Second a subgroup analysis among operated AP patients with a two-year follow-up was performed. Complication rate, radiographic parameters, and clinical scores (ODI, SF-36) were compared in a multivariate analysis between patients who did and did not maintain an AP at the 2-year follow-up., Results: A total of 1163 patients were available for the first analysis. The RPV method seemed to be the most appropriate to define AP in ASD patient. For the second analysis, data on 410 subjects were available, and most of them were young adults with idiopathic scoliosis that did not require pelvic fixation. AP patients who maintained an AP after ASD surgery presented comparable radiographic and clinical outcomes to the patients who presented a normoverted/retroverted pelvis after surgery., Conclusions: According to the results of the presented study, the RPV method is the most appropriate to define primary AP, which is not a pathologic condition and is most often observed in young adults with idiopathic scoliosis. Anteverted pelvis does not require direct surgical correction in this patient group., Competing Interests: LB Consultant: Spineart, Spinevision; I.O.: Royalties : Spineart, alphatec, Clariance, Consultant : Medtronic, Depuy, spinevision Research support : Medtronic, Depuy; JP Consultant: Medtronic, Grants: Medtronic Depuy; F.P.: Research support: DePuySpine Synthes/Medtronic/Nuvasive/Orthofix/SpineArt Consultant: Medtronic/Nuvasive; A.A.: Consultancy: Globus, Zimvie, Research Grant: Depuy, Medtronic Royalty: Zimvie; F.K.: Depuy Spine Speakers Bureau and Research Grant; YPC: Consultant: Clariance, Stryker, Ceraver, Spinevision, Research Grants: Clariance, Stryker, Medtronic; C.Y.: Consultant, Medtronic. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The E3 ubiquitin ligase thyroid hormone receptor interacting protein 12 (TRIP12) has been implicated in pancreatic adenocarcinoma (PDAC) through its role in mediating the degradation of pancreas transcription factor 1a (PTF1a). PTF1a is a transcription factor essential for the acinar differentiation state that is notably diminished during the early steps of pancreatic carcinogenesis. Despite these findings, the direct involvement of TRIP12 in the onset of pancreatic cancer has yet to be established. In this study, we demonstrated that TRIP12 protein was significantly upregulated in human pancreatic preneoplastic lesions. Furthermore, we observed that TRIP12 overexpression varied within PDAC samples and PDAC-derived cell lines. We further demonstrated that TRIP12 was required for PDAC-derived cell growth and for the expression of E2F-targeted genes. Acinar-to-ductal cell metaplasia (ADM) is a reversible process that reflects the high plasticity of acinar cells. ADM becomes irreversible in the presence of oncogenic Kras mutations and leads to the formation of preneoplastic lesions. Using two genetically modified mouse models, we showed that a loss of TRIP12 prevented acini from developing ADM in response to pancreatic injury. With two additional mouse models, we further discovered that a depletion of TRIP12 prevented the formation of Kras G12D -induced preneoplastic lesions and impaired metastasis formation in the presence of mutated Kras G12D and Trp53 R172H genes. In summary our study identified an overexpression of TRIP12 from the early stages of pancreatic carcinogenesis and proposed this E3 ubiquitin ligase as a novel regulator of acinar plasticity with an important dual role in initiation and metastatic steps of PDAC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Purpose: To assess, in a large population of Adult Spinal Deformity (ASD) patients, the true interest of varying the upper anchors as a protective measure against Proximal Junctional Kyphosis (PJK), by analyzing and comparing 2 groups of patients defined according to their proximal construct. Another objective of the study is to look for any other factors, radiological or clinical, that would affect the occurrence of the proximal failure., Methods: Retrospective review of a prospective ASD database collected from 5 centers. Inclusion criteria were age of at least 18 years, presence of a spinal deformity with instrumentation from T12 or above to the pelvis, with minimum 2 years of follow-up. Demographic data, spinopelvic parameters, functional outcomes and complications were collected. Multiple logistic regression analysis was performed to identify the risk factors that would affect the occurrence of PJK., Results: 254 patients were included. 166 in the group "screws proximally" (SP) and 88 in the group "hooks proximally" (HP). There was no difference between both groups for PJK (p = 0.967). The occurrence of PJK was rather associated with greater age and BMI, higher preoperative kyphosis, worst preoperative SRS22 and SF36 scores, greater postoperative Sagittal Vertical Axis (SVA), coronal malalignment and kyphosis., Conclusion: The use of proximal hooks was not effective to prevent PJK after ASD surgery, when compared to proximal screws. Worse preoperative functional outcomes and worse postoperative sagittal and also coronal malalignment were the main drivers for the occurrence of PJK regardless the type of proximal implant., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The Minimal Clinically Important Difference (MCID) is crucial to evaluate management outcomes, but different thresholds have been obtained in different works. Part of this variability is due to measurement error and influence of the database, both essential for calculating the MCID. The aim of this study was to introduce the association of the ROC method in the anchor-based MCID calculation for ODI, SRS-22r, and SF-36, to objectively set the threshold for the anchor-based MCID in an adult spine deformity (ASD) population., Methods: Multicentric study based on a prospective database of consecutively operated ASD patients. An anchor question was used to assess patients' quality of life after surgery. Different approaches were used to calculate the MCID and then compared: SEM (Standard Error of Measurement), MDC (Minimal Detectable Change), and anchor-based MCID with ROC method., Results: 516 patients were included. Those who responded with 6 and 7 to the anchor question were considered improved. The MCID ranges obtained with the ROC method exhibited the lowest variability. Prediction error rates ranged from 31% (SRS-22r) to 41% (SF-36 MCS). The MCID ranges spanned between 12 and 15 for ODI, 0.6 and 0.73 for SRS-22r, 6.62 and 7.41 for SF-36 PCS, and between 2.69 and 5.63 for SF-36 MCS., Conclusion: The ROC method proposes an MCID range with error rate, and can objectively determine the threshold for distinguishing improved and non-improved patients. As the MCID correlates with the utilized database and error of measurement, each study should compute its own MCID for each PROM to allow comparison among different publications., Level of Evidence: II., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The relationship between rod curvature and postoperative radiographic results is a debated topic. One of the reasons of the heterogeneity of the observed results might reside in the lack of a validated and widely employed method to measure the curvature of the rods. Aim of this study was to present and validate a novel method for rod measurement, which is based on routine X-rays and utilizes a regression algorithm that limits manual measurements and the related errors., Methods: Data from 20 adolescent idiopathic scoliosis/Scheuermann kyphosis (AIS/SK) patients and 35 adult spine deformity (ASD) patients for analysis, with 112 rods in total. An orthogonal reference grid was overlaid on the lateral X-ray; seven points were then marked along each rod and their coordinates recorded in a table. Using these coordinates, a third-order polynomial regression was applied to obtain the rod curvature equation (correlation coefficients > 0.97). Three observers (one surgeon, one experienced and one inexperienced observer) independently applied the developed method to measure the rod angulation of the included patients and performed the measurements twice. The reliability of the method was evaluated in terms of intraclass correlation coefficient (ICC), Bland-Altmann plot and 2S R ., Results: The intra-observer ICCs for all measurements exceed 0.85, indicating an excellent correlation. For the AIS/SK group, the surgeon showed a slightly lower reliability compared to the other two evaluators (0.93 vs 0.98 and 0.98). However, the surgeon showed a higher reliability in measurements of the rods at the lumbar level, both for L1-S1 and L4-S1 (0.98 vs 0.96 and 0.89; 0.97 vs. 0.85 and 0.91, respectively). The variability also showed excellent results, with a mean variability ranging from 1.09° to 3.76°. The inter-observer ICCs for the three measurement groups showed an excellent reliability for the AIS/SK group (0.98). The reliability was slightly lower but still excellent for the lumbar measurements in ASD patients at L1-S1 (0.89) and L4-S1 (0.83). The results of the 2S R for each measured segment were 4.4° for T5-T11, 5.4° for L1-S1 and 5.5° for L4-S1., Conclusion: The described method represents a reliable and reproducible way to measure rod curvature. This method is based on routine X-rays and utilizes a regression algorithm that limits manual measurements and the related errors., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Purpose: To compare the sagittal alignment of patients with diverse mechanical complications (MCs) following adult spinal deformity (ASD) surgery with that of patients without MCs., Methods: A total of 371 patients who underwent ASD surgery were enrolled. The sagittal spinopelvic parameters were measured preoperatively and at the 6-month and last follow-up, and the global alignment and proportion (GAP) score was calculated. The subjects were divided into non-MC and MCs groups, and the MCs group was further divided into rod fracture (RF), screw breakage (SB), screw dislodgement (SD) and proximal junctional kyphosis (PJK) subgroups., Results: Preoperatively, the RF group had greater thoracolumbar kyphosis (TLK) and relative upper lumbar lordosis (RULL); the SB group had the largest pelvic incidence (PI) and lumbar lordosis (LL); the SD group had the least global sagittal imbalance; and the PJK group had the highest thoracic kyphosis (TK), TLK and RULL. At the last follow-up, the RF and SB groups featured a large PI minus LL (PI-LL), while the PJK group featured a prominent TK; all the MCs subgroups had sagittal malalignment and a higher GAP score, and the SB group had the most severe cases. Logistic regressions showed that the relative spinopelvic alignment (RSA) score was correlated with RF, SB and SD, while the RSA and age scores were associated with PJK., Conclusion: Each patient with MCs had individual characteristics in the sagittal plane following ASD surgery, which may be helpful to understand the pathophysiology of poor sagittal alignment with its subsequent MCs and guide an eventual revision strategy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)