Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. RESULTS: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). CONCLUSION: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Phenotype Prevalence and Health-Related Quality of Life of Lebanese Women With Polycystic Ovary Syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Our study aimed to assess, for the first time, the phenotype prevalence and the health-related quality of life of Lebanese women with PCOS. METHODS: This was a cross-sectional study conducted on 322 Lebanese women with PCOS, using a questionnaire containing sociodemographic data, comorbidities, disease-related clinical questions, and the validated PCOS questionnaire (PCOSQ). The quality of life mean scores and phenotypes were compared and correlated among the different sociodemographic data, comorbidities, and disease-related questions. RESULTS: Phenotype A (67%) was the most common phenotype. High waist circumference and higher Body Mass Index (BMI) were reported mostly in classic phenotypes in comparison with nonclassic (P < .05). The mean total score of all PCOSQ domains was 3.61 ± 1.60. The mean score for each domain (from the greatest to the least serious concern) was menstrual problems (3.31 ± 1.26), emotion (3.33 ± 1.22), weight (3.41 ± 2.12), body hair (3.86 ± 1.79), and infertility (4.15 ± 1.61). Age was negatively correlated only to weight domain score (r = -0.17, P = .002). BMI was associated only with emotion and weight domain scores (P = .017 and P < .001, respectively). A bigger impairment in nearly all subscales of the PCOSQ in patients presenting with abdominal obesity, glucose intolerance, and increased blood pressure was noted (P < .05). CONCLUSION: Most Lebanese women with PCOS present phenotype A and have a serious impairment in their health-related quality of life, particularly in the menstrual and emotional domains. This highlights the need for community and individual support.

Assessment of dynamic balance during walking in patients with adult spinal deformity.

PURPOSE: To assess dynamic postural alignment in ASD during walking using a subject-specific 3D approach. METHODS: 69 ASD (51 ± 20 years, 77%F) and 62 controls (34 ± 13 years, 62%F) underwent gait analysis along with full-body biplanar Xrays and filled HRQoL questionnaires. Spinopelvic and postural parameters were computed from 3D skeletal reconstructions, including radiographic odontoid to hip axis angle (ODHA) that evaluates the head's position over the pelvis (rODHA), in addition to rSVA and rPT. The 3D bones were then registered on each gait frame to compute the dynamic ODHA (dODHA), dSVA, and dPT. Patients with high dODHA (> mean + 1SD in controls) were classified as ASD-DU (dynamically unbalanced), otherwise as ASD-DB (dynamically balanced). Between-group comparisons and relationship between parameters were investigated. RESULTS: 26 patients were classified as ASD-DU having an average dODHA of 10.4° (ASD-DB: 1.2°, controls: 1.7°), dSVA of 112 mm (ASD-DB: 57 mm, controls: 43 mm), and dPT of 21° (ASD-DB: 18°, controls: 14°; all p < 0.001). On static radiographs, ASD-DU group showed more severe sagittal malalignment than ASD-DB, with more altered HRQoL outcomes. The ASD-DU group had an overall abnormal walking compared to ASD-DB & controls (gait deviation index: 81 versus 93 & 97 resp., p < 0.001) showing a reduced flexion/extension range of motion at the hips and knees with a slower gait speed and shorter step length. Dynamic ODHA was correlated to HRQoL scores. CONCLUSION: Dynamically unbalanced ASD had postural malalignment that persist during walking, associated with kinematic alterations in the trunk, pelvis, and lower limbs, making them more prone to falls. Dynamic-ODHA correlates better with HRQoL outcomes than dSVA and dPT.

Global malalignment in adolescent idiopathic scoliosis: the axial deformity is the main driver.

PURPOSE: To evaluate the global alignment of non-operated subjects with adolescent idiopathic scoliosis. METHOD: A total of 254 subjects with AIS and 64 controls underwent low dose biplanar X-rays and had their spine, pelvis, and rib cage reconstructed in 3D. Global alignment was measured in the sagittal and frontal planes by calculating the OD-HA angle (between C2 dens to hip axis with the vertical). Subjects with AIS were classified as malaligned if the OD-HA was > 95th percentile relative to controls. RESULTS: The sagittal OD-HA in AIS remained within the normal ranges. In the frontal plane, 182 AIS were normally aligned (Group 1, OD-HA = 0.9°) but 72 were malaligned (Group 2, OD-HA = 2.9°). Group 2 had a more severe spinal deformity in the frontal and horizontal planes compared to Group 1 (Cobb: 42 ± 16° vs. 30 ± 18°; apical vertebral rotation AVR: 19 ± 10° vs. 12 ± 7°, all p < 0.05). Group 2 subjects were mainly classified as Lenke 5 or 6. 19/72 malaligned subjects had a mild deformity (Cobb < 30°) but a progressive scoliosis (severity index ≥ 0.6). The frontal OD-HA angle was found to be mainly determined (adjusted-R2 = 0.22) by the apical vertebral rotation and secondarily by the Lenke type. CONCLUSIONS: This study showed that frontal malalignment is more common in distal major structural scoliosis and its main driver is the apical vertebral rotation. This highlights the importance of monitoring the axial plane deformity in order to avoid worsening of the frontal global alignment.

Alterations of gait kinematics depend on the deformity type in the setting of adult spinal deformity.

PURPOSE: To evaluate 3D kinematic alterations during gait in Adult Spinal Deformity (ASD) subjects with different deformity presentations. METHODS: One hundred nineteen primary ASD (51 ± 19y, 90F), age and sex-matched to 60 controls, underwent 3D gait analysis with subsequent calculation of 3D lower limb, trunk and segmental spine kinematics as well as the gait deviation index (GDI). ASD were classified into three groups: 51 with sagittal malalignment (ASD-Sag: SVA > 50 mm, PT > 25°, and/or PI-LL > 10°), 28 with only frontal deformity (ASD-Front: Cobb > 20°) and 40 with only hyperkyphosis (ASD-HyperTK: TK > 60°). Kinematics were compared between groups. RESULTS: ASD-Sag had a decreased pelvic mobility compared to controls with a decreased ROM of hips (38 vs. 45°) and knees (51 vs. 61°). Furthermore, ASD-Sag exhibited a decreased walking speed (0.8 vs. 1.2 m/s) and GDI (80 vs. 95, all p < 0.05) making them more prone to falls. ASD-HyperTK showed similar patterns but in a less pronounced way. ASD-Front had normal walking patterns. GDI, knee flex/extension and walking speed were significantly associated with SVA and PT (r = 0.30-0.65). CONCLUSION: Sagittal spinal malalignment seems to be the driver of gait alterations in ASD. Patients with higher GT, SVA, PT or PI-LL tended to walk slower, with shorter steps in order to maintain stability with a limited flexibility in the pelvis, hips and knees. These changes were found to a lesser extent in ASD with only hyperkyphosis but not in those with only frontal deformity. 3D gait analysis is an objective tool to evaluate functionality in ASD patients depending on their type of spinal deformity. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Toward understanding the underlying mechanisms of pelvic tilt reserve in adult spinal deformity: the role of the 3D hip orientation.

PURPOSE: To explore 3D hip orientation in standing position in subjects with adult spinal deformity (ASD) presenting with different levels of compensatory mechanisms. METHODS: Subjects with ASD (n = 159) and controls (n = 68) underwent full-body biplanar X-rays with the calculation of 3D spinopelvic, postural and hip parameters. ASD subjects were grouped as ASD with knee flexion (ASD-KF) if they compensated by flexing their knees (knee flexion ≥ 5°), and ASD with knee extension (ASD-KE) otherwise (knee flexion < 5°). Spinopelvic, postural and hip parameters were compared between the three groups. Univariate and multivariate analyses were then computed between spinopelvic and hip parameters. RESULTS: ASD-KF had higher SVA (67 ± 66 mm vs. 2 ± 33 mm and 11 ± 21 mm), PT (27 ± 14° vs. 18 ± 9° and 11 ± 7°) and PI-LL mismatch (20 ± 26° vs - 1 ± 18° and - 13 ± 10°) when compared to ASD-KE and controls (all p < 0.05). ASD-KF also had a more tilted (34 ± 11° vs. 28 ± 9° and 26 ± 7°), anteverted (24 ± 6° vs. 20 ± 5° and 18 ± 4°) and abducted (59 ± 6° vs. 57 ± 4° and 56 ± 4°) acetabulum, with a higher posterior coverage (100 ± 6° vs. 97 ± 7° for ASD-KE) when compared to ASD-KE and controls (all p < 0.05). The main determinants of acetabular tilt, acetabular abduction and anterior acetabular coverage were PT, SVA and LL (adjusted R2 [0.12; 0.5]). CONCLUSIONS: ASD subjects compensating with knee flexion have altered hip orientation, characterized by increased posterior coverage (acetabular anteversion, tilt and posterior coverage) and decreased anterior coverage which can together lead to posterior femoro-acetabular impingement, thus limiting pelvic retroversion. This underlying mechanism could be potentially involved in the hip-spine syndrome.

Update on Biomarkers in Renal Cell Carcinoma.

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.

Efficacy and safety of the enzymatic mixture - Lipase, collagenase and hyaluronidase - In the treatment of moderate to severe submental fat: A prospective cohort study.

Purpose: To study the effect of the enzymatic mixture: Lipase, Collagenase and Hyaluronidase in the treatment of submental fat. Methods: A monocentric prospective cohort study including 10 female patients, aged between 18 and 65 years old, who received treatment for submental fat with a mixture of Lipase, Collagenase, and Hyaluronidase. The treatment protocol consisted of one treatment session every 21 days for a total of 3 sessions. In each session, 4 ml of the enzymatic mixture (1 ml of Collagenase GH PB20, 1 ml of Hyaluronidase PB 3000 and 2 ml of Lipase PB 500) + 2 ml of Lidocaine 2% were injected in the submental fat (SMF). Efficacy was assessed four weeks after the last session. Co-Primary Outcome was defined as the improvement of ≥ 1-point in Clinician-Reported and Patient-Reported Sub-mental Fat Rating Scales (CR-SMFRS and PR-SMFRS). Secondary Outcomes included score reductions in Patient-Reported Sub-mental Fat Impact Scale (PR-SMFIS), ≥10% reduction in submental fat pad thickness by ultrasound, and Subject Self-Rating Scale (SSRS) responses of 4, 5, or 6. Results: The Co-Primary outcome was achieved in 9 out of 10 patients. A considerable reduction of 22.8% in the PR-SMFIS was observed. Furthermore, 9 out of 10 patients expressed overall satisfaction with the treatment. Submental fat reduction of more than 10% was observed in 9 out of 10 patients in neutral position and in all patients in flexed position. Adverse effects were only limited to local reactions. Conclusion: The enzymatic mixture of Lipase, Collagenase and Hyaluronidase is an effective and safe minimally-invasive method for the reduction of SMF that can be used alone or in conjunction with other treatment modalities.

Kinematic adaptations from self-selected to fast speed walking in patients with adult spinal deformity.

PURPOSE: To investigate kinematic adaptations from self-selected to fast speed walking in ASD patients. METHODS: 115 primary ASD and 66 controls underwent biplanar radiographic X-rays and 3D gait analysis to calculate trunk, segmental spine and lower limb kinematics during self-selected and fast speed walking. Kinematic adaptation was calculated as the difference (Δ) between fast and self-selected speed walking. ASD with 7 or more limited kinematic adaptation parameters were classified as ASD-limited-KA, while those with less than 7 limited kinematic adaptation parameters were classified as ASD-mild-KA. RESULTS: 25 patients were classified as ASD-limited-KA and 90 as ASD-mild-KA. ASD-limited-KA patients walked with a lesser increase of pelvic rotation (Δ = 1.7 vs 5.5°), sagittal hip movement (Δ = 3.1 vs 7.4°) and shoulder-pelvis axial rotation (Δ = 3.4 vs 6.4°) compared to controls (all p < 0.05). ASD-limited-KA had an increased SVA (60.6 vs - 5.7 mm), PT (23.7 vs 11.9°), PI-LL (9.7 vs - 11.7°), knee flexion (9.2 vs - 0.4°) and a decreased LL (44.0 vs 61.4°) compared to controls (all p < 0.05). Kinematic and radiographic alterations were less pronounced in ASD-mild-KA. The limited increase of walking speed was correlated to the deteriorated physical component summary score of SF-36 (r = 0.37). DISCUSSION: Kinematic limitations during adaptation from self-selected to fast speed walking highlight an alteration of a daily life activity in ASD patients. ASD with limited kinematic adaptations showed more severe sagittal malalignment with an increased SVA, PT, PI-LL, and knee flexion, a decreased LL and the most deteriorated quality of life. This highlights the importance of 3D movement analysis in the evaluation of ASD.

Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes.

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.

Clinicodemographic characteristics of extraosseous ewing sarcoma: A comparative meta-analysis of pediatric and adult patients.

Background: Evidence suggests different presentation patterns and prognosis of extraosseous Ewing Sarcoma (EES) based on age. Thus, we carried out this study to test the difference between children and adult EES cases regarding clinicodemographic characteristics and prognosis. Methods: A total of 4 databases were explored yielding 18 relevant studies for data synthesis. Outcomes included the comparison of demographic and clinical characteristics as well as prognosis between children and adults with EES. Log odds ratio (logOR) and its 95% confidence interval (CI) were pooled across studies. Statistical models/methods were selected based on heterogeneity. Results: Our analysis included a total of 1261 children and 1256 adults. When we compared these two age categories, we did not observe a significant difference in the risk of developing EES [logOR = -0.13; 95% CI: -0.65: 0.39; I2 = 88.42%]. No significant differences regarding gender, tumor location, and size (≤5 vs. >5 cm), EWSR1 positivity, or management modality. We did not observe significant difference regarding clinical outcomes, such as 5-year overall survival and event-free survival, recurrence, mortality, no evidence of disease, and secondary metastasis. Conclusions: Our findings highlight the absence of an association between the age category of patients and the incidence of EES, as well as its clinical outcomes.

Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma.

Patients with metastatic clear cell renal cell carcinoma (mccRCC) experience highly heterogeneous outcomes when treated with standard-of-care systemic regimens. Therefore, valid biomarkers are needed to predict the clinical response to these therapies and help guide management. In this review, the authors outline relevant and promising biomarkers for patients with mccRCC receiving systemic therapies, with a focus on immunotherapy-based regimens.

Novel Immune Therapies for Renal Cell Carcinoma: Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes.

Immunotherapy has revolutionized treatment for patients with advanced and metastatic renal cell carcinoma. Nevertheless, many patients do not benefit or eventually relapse, highlighting the need for novel immune targets to overcome primary and acquired resistance. This review discusses 2 strategies currently being investigated: disabling inhibitory stimuli that maintain immunosuppression ("brakes") and priming the immune system to target tumoral cells ("gas pedals"). We explore each class of novel immunotherapy, including the rationale behind it, supporting preclinical and clinical evidence, and limitations.

Novel Targeted Therapies for Renal Cell Carcinoma: Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition.

Targeted therapies have revolutionized the treatment of renal cell carcinoma (RCC). The VHL/HIF pathway is responsible for the regulation of oxygen homeostasis and is frequently altered in RCC. Targeting this pathway as well as the mTOR pathway have yielded remarkable advances in the treatment of RCC. Here, we review the most promising novel targeted therapies for the treatment of RCC, including HIF2α, MET, metabolic targeting, and epigenomic reprogramming.

ASD with high pelvic retroversion develop changes in their acetabular orientation during walking.

Introduction: It was hypothesized that pelvic retroversion in Adult Spinal Deformity (ASD) can be related to an increased hip loading explaining the occurrence of hip-spine syndrome. Research question: How pelvic retroversion can modify acetabular orientation in ASD during walking? Methods: 89 primary ASD and 37 controls underwent 3D gait analysis and full-body biplanar X-rays. Classic spinopelvic parameters were calculated from 3D skeletal reconstructions in addition to acetabular anteversion, abduction, tilt, and coverage. Then, 3D bones were registered on each gait frame to compute the dynamic value of the radiographic parameters during walking. ASD patients having a high PT were grouped as ASD-highPT, otherwise as ASD-normPT. Control group was divided in: C-aged and C-young, age matched to ASD-hightPT and ASD-normPT respectively. Results: 25/89 patients were classified as ASD-highPT having a radiographic PT of 31° (vs 12° in other groups, p â€‹< â€‹0.001). On static radiograph, ASD-highPT showed more severe postural malalignment than the other groups: ODHA â€‹= â€‹5°, L1L5 â€‹= â€‹17°, SVA â€‹= â€‹57.4 â€‹mm (vs 2°, 48° and 5 â€‹mm resp. in other groups,all p â€‹< â€‹0.001). During gait, ASD-highPT presented a higher dynamic pelvic retroversion of 30° (vs 15° in C-aged), along with a higher acetabular anteversion of 24° (vs 20°), external coverage of 38° (vs 29°) and a lower anterior coverage of 52° (vs 58°,all p â€‹< â€‹0.05). Conclusion: ASD patients with severe pelvic retroversion showed an increased acetabular anteversion, external coverage and lower anterior coverage during gait. These changes in acetabular orientation, computed during walking, were shown to be related to hip osteoarthritis.

Spinopelvic Adaptations in Standing and Sitting Positions in Patients With Adult Spinal Deformity.

Purpose To describe spinopelvic adaptations in the standing and sitting positions in patients with adult spinal deformity (ASD). Methods Ninety-five patients with ASD and 32 controls completed health-related quality of life (HRQOL) questionnaires: short form 36 (SF36), Oswestry Disability Index (ODI), and visual analog scale (VAS) for pain. They underwent biplanar radiography in both standing and sitting positions. Patients with ASD were divided into ASD-front (frontal deformity Cobb > 20°, n = 24), ASD-sag (sagittal vertical axis (SVA) > 50 mm, pelvic tilt (PT) > 25°, or pelvic incidence (PI)-lumbar lordosis (LL) > 10°, n = 40), and ASD-hyper thoracic kyphosis (TK >60°, n = 31) groups. Flexibility was defined as the difference (Δ) in radiographic parameters between the standing and sitting positions. The radiographic parameters were compared between the groups. Correlations between HRQOL scores were evaluated. Results All participants increased their SVA from standing to sitting (ΔSVA<0), except for patients with ASD-sag, who tended to decrease their SVA (78-62 mm) and maximize their pelvic retroversion (27-40° vs 10-34° in controls, p<0.001). They also showed reduced thoracic and lumbar flexibility (ΔLL = 3.4 vs 37.1°; ΔTK = -1.7 vs 9.4° in controls, p<0.001). ASD-hyperTK showed a decreased PT while sitting (28.9 vs 34.4° in controls, p<0.001); they tended to decrease their LL and TK but could not reach values for controls (ΔLL = 22.8 vs 37.1° and ΔTK = 5.2 vs 9.4°, p<0.001). The ASD-front had normal standing and sitting postures. ΔSVA and ΔLL were negatively correlated with the physical component scale (PCS of SF36) and ODI (r = -0.39 and r = -0.46, respectively). Conclusion Patients with ASD present with different spinopelvic postures and adaptations from standing to sitting positions, with those having sagittal malalignment most affected. In addition, changes in standing and sitting postures were related to HRQOL outcomes. Therefore, surgeons should consider patient sitting adaptations in surgical planning and spinal fusion. Future studies on ASD should evaluate whether physical therapy or spinal surgery can improve sitting posture and QOL, especially for those with high SVA or PT.

Reliability assessment of cervical spine parameters measured on full-body radiographs in asymptomatic subjects and patients with spinal deformity.

BACKGROUND: Cervical spinal alignment is usually assessed on full-body radiographs allowing for the concomitant evaluation of possible compensatory mechanisms that may occur at any level in the setting of postural malalignment. HYPOTHESIS: Cervical parameters measured on full-body radiographs are reliable. PATIENTS AND METHODS: A total of 70 subjects were included and divided in 3 groups: asymptomatic adults (n=21), adolescents with idiopathic scoliosis (n=20), and adults with spinal deformity (n=29), for whom full-body low-dose biplanar radiographs were obtained. Eighteen cervical parameters including gaze and cervical curvature, upper cervical spine, global cervical alignment, thoraco-cervical and cervico-pelvic parameters were measured by 4 operators, three times each. The intraclass correlation coefficient (ICC) and the 95% confidence interval (95% CI) where calculated for each parameter and compared between the 3 groups. RESULTS: ICC and the 95% CI were similar between the 3 groups. The measured parameters showed a very high repeatability (ICC>0.8) except for C0-C2, which presented an average repeatability (ICC=0.57). The cSVA, CTPA, C2-SPi, cranial offset, T1-SPi, CBVA and cranial tilt had a 95% CI<2 (° or cm). The TIA, T1-CL and C0-C2 had a 95% CI>6°. DISCUSSION: The poor visibility of the foramen magnum, hard palate, C7, T1, and the sternum on radiographs could explain why certain parameters showed a higher measurement error. The assessment of these error margins is essential for an accurate evaluation of cervical spinal deformities and a proper therapeutic approach. LEVEL OF EVIDENCE: III; retrospective analysis of prospectively collected data.

Gait kinematic alterations in subjects with adult spinal deformity and their radiological determinants.

BACKGROUND: Adults with spinal deformity (ASD) are known to have postural malalignment affecting their quality of life. Classical evaluation and follow-up are usually based on full-body static radiographs and health related quality of life questionnaires. Despite being an essential daily life activity, formal gait assessment lacks in clinical practice. RESEARCH QUESTION: What are the main alterations in gait kinematics of ASD and their radiological determinants? METHODS: 52 ASD and 63 control subjects underwent full-body 3D gait analysis with calculation of joint kinematics and full-body biplanar X-rays with calculation of 3D postural parameters. Kinematics and postural parameters were compared between groups. Determinants of gait alterations among postural radiographic parameters were explored. RESULTS: ASD had increased sagittal vertical axis (SVA:34 ±â€¯59 vs -5 ±â€¯20 mm), pelvic tilt (PT:19 ±â€¯13 vs 11 ±â€¯6°) and frontal Cobb (25 ±â€¯21 vs 4 ±â€¯6°) compared to controls (all p < 0.001). ASD displayed decrease walking speed (0.9 ±â€¯0.3 vs 1.2 ±â€¯0.2 m/s), step length (0.58 ±â€¯0.11 vs 0.64 ±â€¯0.07 m) and increased single support (0.45 ±â€¯0.05 vs 0.42 ±â€¯0.04 s). ASD walked with decreased hip extension in stance (-3 ±â€¯10 vs -7 ±â€¯8°), increased knee flexion at initial contact and in stance (10 ±â€¯11 vs 5 ±â€¯10° and 19 ±â€¯7 vs 16 ±â€¯8° respectively), and decreased knee flexion/extension ROM (55 ±â€¯9 vs 59 ±â€¯7°). ASD had increased trunk flexion (12 ±â€¯12 vs 6 ±â€¯11°) and reduced dynamic lumbar lordosis (-11 ±â€¯12 vs -15 ±â€¯7°, all p < 0.001). Sagittal knee ROM, walking speed and step length were negatively determined by SVA; lack of lumbar lordosis during gait was negatively determined by radiological lumbar lordosis. SIGNIFICANCE: Static compensations in ASD persist during gait, where they exhibit a flexed attitude at the trunk, hips and knees, reduced hip and knee mobility and loss of dynamic lordosis. ASD walked at a slower pace with increased single and double support times that might contribute to their gait stability. These dynamic discrepancies were strongly related to static sagittal malalignment.

Alteration of the Sitting and Standing Movement in Adult Spinal Deformity.

Adults with spinal deformity (ASD) are known to have spinal malalignment affecting their quality of life and daily life activities. While walking kinematics were shown to be altered in ASD, other functional activities are yet to be evaluated such as sitting and standing, which are essential for patients' autonomy and quality of life perception. In this cross-sectional study, 93 ASD subjects (50 ± 20 years; 71 F) age and sex matched to 31 controls (45 ± 15 years; 18 F) underwent biplanar radiographic imaging with subsequent calculation of standing radiographic spinopelvic parameters. All subjects filled HRQOL questionnaires such as SF36 and ODI. ASD were further divided into 34 ASD-sag (with PT > 25° and/or SVA >5 cm and/or PI-LL >10°), 32 ASD-hyperTK (with only TK >60°), and 27 ASD-front (with only frontal malalignment: Cobb >20°). All subjects underwent 3D motion analysis during the sit-to-stand and stand-to-sit movements. The range of motion (ROM) and mean values of pelvis, lower limbs, thorax, head, and spinal segments were calculated on the kinematic waveforms. Kinematics were compared between groups and correlations to radiographic and HRQOL scores were computed. During sit-to-stand and stand-to-sit movements, ASD-sag had decreased pelvic anteversion (12.2 vs 15.2°), hip flexion (53.0 vs 62.2°), sagittal mobility in knees (87.1 vs 93.9°), and lumbar mobility (L1L3-L3L5: -9.1 vs -6.8°, all p < 0.05) compared with controls. ASD-hyperTK showed increased dynamic lordosis (L1L3-L3L5: -9.1 vs -6.8°), segmental thoracic kyphosis (T2T10-T10L1: 32.0 vs 17.2°, C7T2-T2T10: 30.4 vs 17.7°), and thoracolumbar extension (T10L1-L1L3: -12.4 vs -5.5°, all p < 0.05) compared with controls. They also had increased mobility at the thoracolumbar and upper-thoracic spine. Both ASD-sag and ASD-hyperTK maintained a flexed trunk, an extended head along with an increased trunk and head sagittal ROM. Kinematic alterations were correlated to radiographic parameters and HRQOL scores. Even after controlling for demographic factors, dynamic trunk flexion was determined by TK and PI-LL mismatch (adj. R 2 = 0.44). Lumbar sagittal ROM was determined by PI-LL mismatch (adj. R 2 = 0.13). In conclusion, the type of spinal deformity in ASD seems to determine the strategy used for sitting and standing. Future studies should evaluate whether surgical correction of the deformity could restore sitting and standing kinematics and ultimately improve quality of life.