Asymptomatic Adult Volunteers Research Articles

Thoracolumbar Sagittal Morphology and Segmental Inclination: A Cross-sectional Cohort Study of Asymptomatic Adult Volunteers.

A cross-sectional cohort study. To present a normative value reference of spinal segmental inclination stratified by age and pelvic incidence (PI), and to clarify the impact of segmental inclination on spinal sagittal morphology. Thoracolumbar segmental inclination has been shown to correlate with the clinical outcomes of adult spinal deformity surgery. However, there currently exists no normative value reference in a large sample of asymptomatic population. Asymptomatic adult volunteers were enrolled from the community. All volunteers underwent a standing full-spine anteroposterior and lateral radiograph. Lumbar tilt (LT) and thoracic tilt (TT) were measured to quantify the segmental inclination of the lumbar and thoracic spine. Regional curvature, global balance and thoracolumbar apex were analyzed across different age and PI groups. The correlation between sagittal parameters and age was analyzed using Pearson correlation tests. A total of 618 volunteers were included with a mean age of 38.7 ± 17.1 years (range 18 to 82y). As age increased, the LT and TT significantly increased (P<0.001). The LT was significantly correlated with PI (r=0.410, P<0.001), with the low PI group exhibiting a greater negative LT. The TT remained constant across different PI groups. Compared to the young and middle-age groups, the thoracic apex and lumbar apex were located more caudally in the elderly group (P<0.001). Subjects with a more caudal lumbar apex exhibited a greater negative LT, and those with a more caudal thoracic apex exhibited a greater positive TT. The thoracic spine naturally adapts to a relatively neutral position, yet it tends to tilt forward with aging. The physiological lumbar inclination is predominantly determined by the PI value with a slight backward tilt, and tends to counteract the anterior truncal inclination with advanced age. Physiological segmental inclination should be considered in spinal surgical planning.

The Importance of Pelvic Obliquity in Assessing Spinal Coronal Alignment: Normative Values, Demographic, and Radiographic Correlations.

Prospective, cross-sectional study. In a geographically diverse population of asymptomatic volunteers, we sought to report the incidence of pelvic obliquity (PO), establish normative values of PO across patient factors, and assess the correlation of PO with radiographic parameters. PO is defined as the misalignment of the pelvis and can be assessed through several anatomic landmarks. Significant PO, whether caused by leg-length discrepancy or not, can lead to coronal malalignment which causes severe pain and disability. Significant emphasis has been placed on achieving appropriate sagittal alignment in recent decades; however, a greater understanding of coronal alignment is needed, and PO is a crucial aspect of evaluating the coronal plane in adult spinal deformity patients. Asymptomatic adult volunteers, ages 18-80 years, enrolled patients from 5 countries (France, Japan, Singapore, Tunisia, and the United States) in the "multiethnic alignment normative study" cohort (IRB 201812144). The included volunteers had no known spinal disorder(s), no significant neck or back pain (Visual Analog Scale: ≤2; Oswestry Disability Index: ≤20), and no abnormal alignment (Cobb ≤20°). PO was measured in the frontal plane as the distance between the highest points of each acetabulum, calculated along the vertical axis in millimeters (mm). The incidence of PO was defined as PO ≥10mm. Kruskal-Wallis, Wilcoxon rank-sum, Pearson correlation, and linear regression were used. A total of 467 patients were included, and PO values by age, sex, body mass index, and country were provided. The overall incidence of PO ≥10mm was 4.3%, and a nonsignificant trend toward increased PO with age was seen ( P = 0.077). No significant differences were seen in PO between sex, ethnicity, or body mass index groups. No significant correlation existed between PO and other commonly used coronal radiographic measurements. PO ≥10mm occurred in 4.3% of asymptomatic volunteers. Despite the importance of recognizing PO in preventing coronal malalignment, PO did not seem to be associated with other radiographic and demographic information, which underscores the importance of intentionally assessing for any PO before surgery. These results in an asymptomatic population provide a foundation for studying PO in patients with spinal pathology.

The Thoracolumbar Inflection Point in a Population of Asymptomatic Volunteers: A Multi-Ethnic Alignment Normative Study Cohort Study.

Prospective cohort study. To show population variance in the Inflection Point (IP) and its role in defining maximum Thoracic Kyphosis (TK) and Lumbar Lordosis (LL). 468 asymptomatic adult volunteers were included in the Multi-Ethnic Normative Alignment Study (MEANS). To find parameters correlating with IP, the vertebrae and discs were numbered such that C7 was 0, T1 was 1, with T1-T2 disc being 1.5, etc. Statistical analysis was performed by a correlation matrix for IP and the 9 other selected parameters along with linear regressions. The overall mean IP was 12.44 approximately corresponding to T12-L1 disc with the median being 12.50, range was T8-L4. The cohort was then stratified by sex and ethnicity, but there was no significant difference in IP between groups. IP in younger subjects was 13 (L1), compared to 12.5 (T12-L1 disc) in older subjects (P < .05). IP was moderately correlated with the TK apex (r = .66). No strong correlation was found between IP and LL magnitude or apex, TK magnitude, sacral slope, or Pelvic Incidence (PI). In terms of other sagittal parameters, PI and LL demonstrated a significant positive correlation. PI and TK did not have a strong association. The mean IP was at the T12-L1 disc, however IP ranged from T8 to L4. Older subjects tended to have a relatively more cephalad IP. No radiographic variable was found to be a strong predictor of the IP. TK apex was found to have a moderate correlation.

Abstract 93: Utility of the Cytosponge for Aetiological Research in Esophageal Squamous Cell Carcinoma: Proof-of-Concept Pilot Study Using Tobacco-Specific Methylation Markers

Abstract Purpose: Esophageal cancer caused 544,076 deaths in 2020. It has two major subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). A geographically intriguing African Esophageal Cancer Corridor has very high incidence and mortality rates for ESCC. We propose that ESCC research in this corridor might benefit from leveraging advances in tools used for the early detection of EAC, namely using the esophageal sponge cytology. The Cytosponge™ was developed by the University of Cambridge Fitzgerald-laboratory. This pill-on-a-string is an endoscopy-alternative and may form an attractive appropriate health technology in Africa. However, use of the Cytosponge™ for ESCC research in Africa is limited to the CytoSCCAPE study which demonstrated high acceptability and safety of administering the device among 102 asymptomatic adult community volunteers in Kilimanjaro, Tanzania. Methods: In the present proof-of-concept pilot study, we investigated whether FFPE cytology blocks obtained in the CytoSCCAPE study could be used for exposure-specific methylation studies, via two objectives: (i) examine DNA yield from the cytology blocks and (ii) evaluating if the isolated DNA can be used for investigating DNA methylation-based exposure analysis. Here we performed pyrosequencing to compare DNA methylation status of established tobacco-specific methylation markers (CpG cg05575921 &amp; a nearby CpG locus) in ever compared to never tobacco users. Results: Among 102 participants (mean age 50 (SD 12) years, 52% female), 58% (N=58) had good DNA yield (&amp;gt;100 ng), 19 had poor DNA concentration (range 3-54.9ng) and 25 had low DNA concentration (range 60-104ng). In total, 49 (77%) samples passed the quantification stage out of 64 samples that were pyrosequenced. Among these 49 participants, median (IQR) cg05575921 methylation was low overall: 33% (27-44) and did not differ between the 8 ever and 41 never-tobacco users (p=0.85). Hypomethylation in tobacco consumers was not observed, in contrast to work published using blood DNA. Conclusion: We discuss possible reasons for this inconsistency, which include low cellularity and deparaffinization of FFPE sections and provide recommendations for future Cytosponge™ studies for ESCC etiological research. Citation Format: Hannah Simba, Fazlur Rahman Taludkar, Daniel Middleton, Blandina Mmbaga, Alex Mremi, Valerie McCormack. Utility of the Cytosponge for Aetiological Research in Esophageal Squamous Cell Carcinoma: Proof-of-Concept Pilot Study Using Tobacco-Specific Methylation Markers [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 93.

Variation in Lumbar Shape and Lordosis in a Large Asymptomatic Population: A MEANS Study.

Prospective, cross-sectional cohort study. To determine the relationship between lumbar shape and sagittal parameters. Understanding the lumbar shape is vital for deformity surgery. Normative sagittal parameters and spine shape remain unstudied in large, multiethnic, asymptomatic cohorts. A prospective, cross-sectional cohort of 468 asymptomatic volunteers between 18 and 80 years was enrolled across 5 countries. Demographic data and radiographic parameters such as pelvic incidence (PI) were collected. Pearson correlation test and linear regression were used to find the relationship between lumbar lordosis (LL) and other parameters. One-way analysis of variance and Welch 2-sample t test were performed to compare lumbar shape across such categories as PI and lumbar apex followed by post hoc Bonferroni correction if needed. PI was moderately correlated with proximal lumbar lordosis (pLL) ( r = -0.54) and weakly correlated with distal lumbar lordosis (dLL) ( r = -0.16). Thoracic kyphosis (T1-T12) was moderately correlated with pLL ( r = -0.35) and dLL ( r = -0.29). dLL was moderately correlated with LL ( r = 0.64). 2.6% (12/468) of subjects had lumbar apex at L2, 40.2% (188/468) at L3, 56.6% at L4 (265/468), and 0.6% (3/468) at other levels. Mean PI was different between volunteers with the apex at L3 and L4. A lower mean PI was associated with the apex at L4 (49.0°), whereas a higher mean PI was associated with the apex at L3 (55.8°). The mean PI-LL mismatch for volunteers was -5.4° with a range from -35° to 39.7°. PI-LL mismatch increased from a mean of -10.1° in volunteers with low PI to a mean of 2.2° in volunteers with high PI. Age was not correlated with LL ( P = 0.84). In asymptomatic adult volunteers, pLL showed a moderate correlation with PI and increased with PI, whereas dLL showed a weak correlation. The lumbar apex migrated proximally with increasing PI. Segmental lordosis and apex position instead of solely global lordosis should be emphasized. Level III.

Lumbar Lordosis Distribution in Asymptomatic Adult Volunteers: A Systematic Review.

Restoring lumbar lordosis is important for adult spinal deformity surgery. Several reports have suggested that lumbar lordosis distribution has a significant impact on the outcome of surgery, including lumbar distribution index (LDI), proximal lumbar lordosis (PLL), and distal lumbar lordosis (DLL). The features of lumbar lordosis distribution are inconclusive in asymptomatic adults. We sought to evaluate the variation of lumbar lordosis distribution (LDI, PLL, and DLL) and to identify associated factors in asymptomatic adult volunteers. We performed a systematic review of the Embase and Medline databases to identify studies in asymptomatic adult volunteers to evaluate lumbar lordosis distribution including LDI, PLL, and DLL. Twelve articles met eligibility criteria and were included in our review. The respective pooled estimates of mean and variance, respectively, were 65.10% (95% confidence interval [CI]: 62.61-67.58) and 13.70% in LDI, 16.51° (95% CI: 5.54-27.49) and 11.46° in PLL, and 35.47° (95% CI: 32.79-38.18) and 9.10° in DLL. Lumbar lordosis distribution was associated with race, age, sex, body mass index, pelvic incidence, and Roussouly classification. This systematic review found that despite a wide variation in LDI and PLL, DLL is maintained in a narrower range in asymptomatic adult volunteers, especially in white populations. Distal lumbar lordosis may be a more reliable radiographic parameter to restore the lumbar lordosis distribution in preoperative planning.

Normalization technique to build patient specific muscle model in finite element head neck spine.

Finite element models of the head and neck are widely used in automotive and clinical fields to understand spinal biomechanics. These models are developed based on CT and MRI scans of the subjects, but historically the muscle data are obtained from cadaveric specimen. The cadaver data is often obtained from older specimens which commonly have undergone degenerative changes resulting in reduction in muscle cross section area. The objective of the current study is to compare the muscle cross-section area used by various finite element models of neck muscles used in the literature and to develop a normalization technique to scale the MRI muscle cross-section area with those available in the literature. Four male and seven female healthy asymptomatic young adult volunteers enrolled in the study after obtaining necessary approval from Institutional Review Board. T1 and T2 weighted magnetic resonance imaging was performed in neutral upright sitting position wearing military helmet. Muscle cross sectional area was obtained for multifidus muscles from the MRI images. Data was compared with those in the literature. Based on the literature review of prior studies, the cross-sectional area of cadaver specimens was smaller than the MRI obtained muscle area. Multifidus muscle scaling factor was obtained by ratio of sum of MRI cross section area with that of cadaver data. Based on the analysis, the scaling factor for male data is 1.6 and for female data is 1.3. the cadaver data can be multiplied by the scaling factor to obtain the MRI specific cross-sectional area. A Normalization technique was developed for scaling MRI data into finite element model. This technique can be used in developing subject specific finite element model of spine which has applications in clinical, automotive, and military environment.

Introduction of a Novel "Segmentation Line" to Analyze the Variations in Segmental Lordosis, Location of the Lumbar Apex, and Their Correlation with Spinopelvic Parameters in Asymptomatic Adults.

Study Design Cross-sectional study.Purpose This study aimed to understand the sagittal spinopelvic parameters, segmental lumbar parameters, and lumbar apex location in asymptomatic adults and analyze their correlations with each other.Overview of Literature Roussouly and his colleagues reported that pelvic incidence (PI) influences the lower arc of lumbar lordosis, whereas Pesenti and his colleagues reported that PI influences only the proximal part of lordosis and not the distal part. Both studies have their shortcomings.Methods One hundred asymptomatic adult volunteers (mean age, 29.1±7.9 years; 69 males, 31 females) who satisfied the selection criteria were enrolled in this study. Standing antero-posterior and lateral whole spine and pelvis X-rays were performed, and the radiographic parameters were analyzed. We introduced a “segmentation line” bisecting the apical vertebra/disk to divide the upper arc of lumbar lordosis (ULL) and lower arc of lumbar lordosis (LLL).Results The mean PI was 48.02°, ULL 29.12°, LLL 16.02°, total lumbar lordosis (TLL) 45.14°, lumbar tilt angle 4.73°, and location of the apex of lumbar lordosis (LLA) 4.11°. The location of the lumbar apex moved higher as the PI increased. The PI was strongly positively correlated with the LLL (r =0.582, p <0.001) and TLL (r =0.579, p <0.001) but not with the ULL (r =0.196, p =0.05). The LLA was strongly positively correlated with the ULL (r =0.349, p <0.001), negatively with the LLL (r =−0.63, p <0.001), and not correlated with the TLL (r =−0.177, p =0.078).Conclusions The PI influences the location of the lumbar apex, the LLL, and the TLL but not the ULL. The location of the lumbar apex significantly influences the segmental lordosis but not the TLL.

Age- and Gender-based Global Sagittal Spinal Alignment in Asymptomatic Adult Volunteers: Results of the Multiethnic Alignment Normative Study (MEANS)

Multicenter Cohort. Assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender. Our understanding of ideal sagittal alignment is still evolving. The Multiethnic Alignment Normative Study (MEANS) investigated skeletal alignment of the largest multiethnic cohort of asymptomatic adult volunteers. We aim to assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender. Asymptomatic volunteers between the ages of 18-80 years were enrolled prospectively and then analyzed retrospectively from six different centers. Volunteers included reported no significant neck or back pain, nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low-dose stereoradiograph. MEANS consisted of 468 volunteers with a mean age of 40.4±14.8 years. Thoracic kyphosis (TK) from T4 to T12 showed a mean of 37.4±10.9°. The average L1-S1 lumbar lordosis (LL) was -57.4±11.3°. LL did not show significant differences across the five age groups. TK showed a significant difference based on age ( P <0.0001). Sagittal vertical axis increased across age groups from -14.2mm in young adults to 17.0mm in patients >64. Similar trend was seen for T1 pelvic angle with a mean of 5.0° in young adults and 13.7° in those older than age 64. Knee flexion increased across age groups without a significant change in odontoid-knee distance which is a surrogate for the center of the head aligned over the knees. In asymptomatic volunteers, sagittal alignment parameters showed a slow and steady change across age groups exemplified by an increase in TK. However, LL did not show a significant decrease across age groups. Volunteers used compensatory mechanisms such as slight pelvis retroversion, knee flexion, and neck extension to maintain an aligned sagittal posture with their head centered over their knees (odontoid-knee). 3.

Phantom-based correction for standardization of myocardial native T1 and extracellular volume fraction in healthy subjects at 3-Tesla cardiac magnetic resonance imaging

ObjectivesTo investigate the effect of the phantom-based correction method for standardizing myocardial native T1 and extracellular volume fraction (ECV) in healthy subjects.MethodsSeventy-one healthy asymptomatic adult (≥ 20 years) volunteers of five different age groups (34 men and 37 women, 45.5 ± 15.5 years) were prospectively enrolled in three academic hospitals. Cardiac MRI including Modified Look - Locker Inversion recovery T1 mapping sequence was performed using a 3-Tesla system with a different type of scanner for each hospital. Native T1 and ECV were measured in the short-axis T1 map and analyzed for mean values of the 16 entire segments. The myocardial T1 value of each subject was corrected based on the site-specific equation derived from the T1 Mapping and ECV Standardization phantom. The global native T1 and ECV were compared between institutions before and after phantom-based correction, and the variation in native T1 and ECV among institutions was assessed using a coefficient of variation (CoV).ResultsThe global native T1 value significantly differed between the institutions (1198.7 ± 32.1 ms, institution A; 1217.7 ± 39.9 ms, institution B; 1232.7 ± 31.1 ms, institution C; p = 0.002), but the mean ECV did not (26.6–27.5%, p = 0.355). After phantom-based correction, the global native T1 and ECV were 1289.7 ± 32.4 ms and 25.0 ± 2.7%, respectively, and CoV for native T1 between the three institutions decreased from 3.0 to 2.5%. The corrected native T1 value did not significantly differ between institutions (1284.5 ± 31.5 ms, institution A; 1296.5 ± 39.1 ms, institution B; 1291.3 ± 29.3 ms, institution C; p = 0.440), and neither did the ECV (24.4–25.9%, p = 0.078).ConclusionsThe phantom-based correction method can provide standardized reference T1 values in healthy subjects.Key Points• After phantom-based correction, the global native T1 of 16 entire myocardial segments on 3-T cardiac MRI is 1289.4 ± 32.4 ms, and the extracellular volume fraction was 25.0 ± 2.7% for healthy subjects.• After phantom - based correction was applied, the differences in the global native T1 among institutions became insignificant, and the CoV also decreased from 3.0 to 2.5%.

Age and Gender Based Spinopelvic and Regional Spinal Alignment in Asymptomatic Adult Volunteers: Results of the Multi-Ethnic Alignment Normative Study (MEANS).

Spinal alignment can have a significant impact on a patient's overall quality of life. Predicting the ideal sagittal spinal alignment of a specific individual is still a difficult task. The Multi-Ethnic Alignment Normative Study (MEANS) investigated skeletal alignment, including the spine and lower extremities, of the largest multi-ethnic cohort of asymptomatic adult volunteers. In this analysis, the authors aim to assess normative values of spinopelvic parameters and the regional cervical, thoracic, and lumbar spinal alignment in asymptomatic volunteers stratified by age and sex. Asymptomatic volunteers between ages 18 and 80 years were enrolled prospectively from centers in France, Japan, Singapore, Tunisia, and the United States. Volunteers included reported no significant neck or back pain (Visual Analog Scale ≤2), nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low-dose stereoradiograph. MEANS consisted of 468 volunteers with a mean age of 40.4±14.8 years. Mean cervical lordosis from C2 to C7 was -0.4±12.7°. The T1-slope averaged 23.0±7.9° and showed strong correlation ( r =0.87) with the C7-slope mean of 19.8±8.6°. Thoracic kyphosis (TK) from T4 to T12 showed a mean of 37.4±10.9°. Average L1-S1 lumbar lordosis (LL) was -57.4±11.3°. The mean pelvic incidence (PI) measured 52.0±10.7° and pelvic tilt was 12.5±7.3°. Sacral slope averaged 39.5±8.2°. The average PI-LL was -5.4±10.7°. Approximately 60% of volunteers met the PI-LL criteria within ±10°, 8.3% were ≥10°, while 32.1% were ≤-10°. LL showed moderate correlation with PI ( r =0.53) and TK ( r =0.50), while there was no correlation between TK and PI. Multiple linear regression including PI, TK, and age resulted in the following equation LL=14.6+0.57 (PI)+0.57 (TK)-0.2 (age) ( r =0.75). LL did not change with increasing age in asymptomatic volunteers. However, TK did increase with age leading to an increase in T1-slope and a compensatory increase in cervical lordosis. TK did not correlate with PI and was an independent variable in the prediction of LL. Level II-prospective cohort study.

Correlation analysis of the PI-LL mismatch according to the pelvic incidence from a database of 468 asymptomatic volunteers.

Previous studies on adults with degenerative scoliosis (ADS) have been fixed the threshold of PI-LL mismatch less than 10° for achieving good clinical outcomes. Recent studies discussed that PI-LL mismatch should consider individual pelvic incidence (PI) and should be set first in a normal population. The purpose of this study is to assess the variability of PI-LL mismatch according to PI in an asymptomatic population. Full-body low dose stereoradiographic evaluation was done in a multi-ethnic cohort of 468 asymptomatic adult volunteers. Patients were clustered in three groups depending on individual PI values: PI < 45°, 45° < PI < 60° and PI > 60°. 3D measurements were performed using a commercially available 2D/3D modeling software to establish a correlation of PI with other spinopelvic parameters. ANOVA and Tukey's HSD for post-hoc analysis were used to determine the differences between the three groups. In our asymptomatic population, the mean value of PI-LL mismatch is -5.4° ± 10.7°. Clusterization of the population reveals significant differences in the distribution of L1S1 lordosis, pelvic tilt and PI-LL with positive linear correlation according to PI values. As an interestingly result, PI-LL mismatch is equal to 0° when PI is around 64°. The present study demonstrated that PI-LL mismatch is negative in an asymptomatic population (-5.4° ± 10.7°) and the value should be customized to each patient to be able to restore the appropriate lordosis in ADS. The PI-LL mismatch is given by the formula PI-LL = -28.5 + 0.44 × PI.

High resolution T2∗ mapping in assessment of knee articular cartilage on 3T MRI

ObjectiveTo evaluate the spectrum of T2∗ values in healthy cartilage of young asymptomatic adults on high resolution 3T MRI. MethodsA total of 50 asymptomatic adult volunteers with age ranging from 18 to 35 years were enrolled for the study with the purpose of assessing T2∗ values in healthy cartilage without any degenerative changes. The articular cartilage was assessed on two sections, one each through the medial and lateral compartments. The cartilage was segmented into 8 regions through the tibio-femoral and patella-femoral joints. Further post processing was done using multiple ROI placement to delineate ROI areas for calculation of full thickness and zonal (superficial and deep) T2∗ values. Thus, a total of 1200 ROI areas (50 volunteers, 8 segments, and 3 areas for each segment) were assessed. ResultsThe results revealed a superior bulk T2∗ value of 29.2 ± 3.6 ms from the posterior medial femoral cartilage and 26.1 ± 3.1 ms from the patellar region. Intermediate values were obtained from posterior lateral femoral cartilage, central femoral cartilage, and trochlea. The tibial plateau cartilage had the lowest values – 19.6 ± 2.6 ms for the medial tibial plateau and 20.6 ± 2.8 ms for lateral tibial plateau. The study demonstrated substantial regional physiological variation existing in the T2∗ values across various regions of the knee joint, which could be attributed to varying amounts of shearing forces across the joint. No significant differences were noted in bulk T2∗ values between the two genders, with only the trochlear segment revealing significantly increased values in males (p = 0.007). All the cartilage segments revealed significantly increased T2∗ values in the superficial zone as compared to the deep zone. ConclusionThere is a significant regional difference in the bulk T2∗ values of articular cartilage in a normal physiological state across various joint segments. A zonal gradient with increasing values from the deep to the superficial zone also exists. These findings can prove invaluable in assessing changes in T2∗ values occurring in diseased/degenerative cartilage.

The odontoid-CSVL distance in a global population of asymptomatic volunteers: normative values and implications for spinal coronal alignment.

In a population of asymptomatic volunteers across 5 countries, we sought to: (a) establish normative values of the Odontoid-Central Sacral Vertical Line (OD-CSVL) across patient factors, and (b) assess correlations of OD-CSVL with other radiographic parameters. A prospective, cross-sectional study of asymptomatic adult volunteers, ages 18-80years, were enrolled across 5 countries (France, Japan, Singapore, Tunisia, United States) forming the Multi-Ethnic Alignment Normative Study (MEANS) cohort. Included volunteers had no known spinal disorder(s), no significant neck/back pain (VAS ≤ 2; ODI ≤ 20), and no significant scoliosis (Cobb ≤ 20°). Radiographic measurements included commonly used coronal alignment parameters (mm) and angles (°). OD-CSVL was defined as the difference between the odontoid plumb line (line from the tip of the odontoid vertically down) and the CSVL (vertical line from the center of the sacrum). Chi-square, student's t tests, Kruskal-Wallis, Wilcoxon rank-sum, linear regression, and Pearson's correlation were used with significance at p < 0.05. 467 volunteers were included with normative OD-CSVL values by age decade, gender, BMI, and country. Mean ± SD OD-CSVL was 8.3mm ± 6.5mm and 31 (6.6%) volunteers were almost perfectly aligned (OD-CSVL < 1mm). A linear relationship was seen between OD-CSVL with both age (p < 0.001) and BMI (p = 0.015). Significant variation was seen between OD-CSVL and 5 different ethnicities (p = 0.004). OD-CSVL correlated best with other coronal radiographic parameters, C7-CSVL (r = 0.743, p < 0.001), OD-knee (r = 0.230, p < 0.001), CAM-knee (r = 0.612, p < 0.001), and regional TL cobb angle (r = 0.4214, p = 0.005). Among asymptomatic volunteers, increased OD-CSVL was significantly associated with increased age, increased BMI, and ethnicity, but not gender. OD-CSVL correlated strongest with C7-CSVL, TL cobb angle, OD-knee, and CAM-knee. OD-CSVL. These results support further study of OD-CSVL in symptomatic adult spine deformity patients.

Lumbar lordosis morphology correlates to pelvic incidence and erector spinae muscularity

The retrospective study aimed to investigate the relationship between lumbar lordosis morphology, pelvic incidence and paraspinal muscle. It enrolled asymptomatic adult volunteers aged between 18 and 45 years old. Lumbar lordosis morphology, consisting of total lumbar lordosis (LL), proximal lumbar lordosis (PLL), distal lumbar lordosis (DLL), lumbar lordosis apex (LLA) and inflexion point, was evaluated, as well as pelvic incidence (PI) and muscularity of erector spinae (ES) and multifidus. Pearson correlation was performed to analyze the relationship between each other parameter. Cases were stratified according to pelvic incidence (very low < 30°, low 30°–45°, moderate 45°–60°, and high > 60°), comparison between groups was performed by univariance analysis. 87 asymptomatic adult volunteers (33 females and 54 males) were included in the study. PLL revealed a correlation with LLA (r = 0.603, p = 0.002) and inflexion point (r = 0.536, p = 0.004), but did not DLL with LL apex (r = 0.204, p = 0.058) or inflexion point (r = 0.210, p = 0.051). PI revealed a greater correlation with PLL (r = −0.673, p < 0.001) than with DLL (r = −0.237, p = 0.045). Linear stepwise regression analysis also exhibited the correlation between PI and PLL (R2 = 0.452, PLL = 16.2–0.61 * PI, p < 0.001). ES muscularity correlated with LL apex (r = −0.279, p = 0.014) and inflexion point (r = −0.227, p = 0.047). Stratification by PI demonstrated PLL increased across groups (p < 0.001), but DLL was comparable between low and moderate PI group (p = 0.329). Lumbar lordosis morphology appears to accommodate to pelvic incidence and erector spinae muscularity. Proximal lumbar lordosis has a bigger correlation with pelvic incidence than the distal lumbar lordosis. The results are helpful for restoring a rational lumbar lordosis shape in long fusion surgery.

Clostridioides difficile Strains in the Gut by Next-Generation Shotgun Sequencing: Innocent Bystander or Villain?

Background: Pathogenic Clostridioides difficile is the most common cause of nosocomial infections in the United States. However, the prevalence of C. difficile colonization in the general population is poorly understood. Objective: In this study, we sought to determine the presence and nature of various strains of Clostridioides difficile colonizing a representative sample of 121 asymptomatic adult volunteers from around the globe, consisting of 110 healthy and 11 stable Crohn’s patients. Methods: Next-generation sequencing was performed on fecal samples from 121 study participants. Stool samples were collected by patients utilizing a Zymo collection kit, which preserves bacterial DNA and RNA. Following collection, DNA was extracted, quantitated, and then normalized for downstream library fabrication utilizing shotgun methodology. Prepared and indexed libraries were subsequently pooled and sequenced on the Illumina NextSeq 550 System. Results: All 121 of 121 subjects (100%) were found to possess the bacterium Clostridioides difficile as identified by the NGS bioinformatics metagenomic pipeline. To visualize comparative abundances of Clostridioides difficile present in study participants, normalized read counts were highlighted (Fig. 1). Conclusions: NGS provides a unique opportunity to increase the resolution and identification of Clostridioides difficile compared to traditional categorizations, such as PCR ribotypes (ie, RT027), restriction endonuclease groups (BI), and North American pulsotypes (ie, NAP1). This is accomplished by its ability to differentiate species based on a nucleotides, while targeting entire bacterial genomes. Our approach for this study was to utilize a bioinformatics pipeline that would provide Clostridioides difficile strain-specific resolution when aligning to genomes in the NCBI (National Center for Biotechnology Information) database. In our representative sample of 121 volunteers, all (100%) possessed at least 1 Clostridioides difficile strain in their gut. Although it is recognized that some Clostridioides difficile strains are pathogenic, our findings suggest that nonpathogenic Clostridioides difficile strains make up an important component of the commensal gut microbiome and may perhaps play a protective role. Although symptomatic toxigenic CDI is a clear indication for therapy, Clostridioides difficile colonization with nontoxigenic strains is not believed to be a direct precursor for CDI. These findings demonstrate the need to be aware of the existence of numerous strains of Clostridioides difficile, and the relevance of sequencing prior to hospitalization or antibiotic treatment to help predict those at risk of CDI, and after treatment to be aware of any loss of what appear to be protective components of our microbiome.Funding: NoneDisclosures: Dr. Sabine Hazan reports that she is the founder and CEO of Ventura Clinical Trials and that she and her spouse receive salaries from the company. She also receives a salary from ProgenaBiome.

Performing High-resolution Impedance Manometry After Endoscopy With Conscious Sedation Has Negligible Effects on Esophageal Motility Results.

Background/AimsHigh-resolution manometry (HRM) performed without sedation is the standard procedure. However, some patients cannot tolerate transnasal placement of the manometry catheter. We aim to assess the practice of performing manometry after endoscopy with conscious sedation by evaluating its impact on esophageal motility findings.MethodsTwelve asymptomatic adult volunteers and 7 adult patients completed high-resolution impedance manometry (HRIM) approximately 1 hour after conscious sedation with midazolam and fentanyl (post-sedation) and again on a different day with no-sedation. The no-sedation HRIM involved 2 series of swallows separated in time by 20 minutes (no-sedation-1 and no-sedation-2) for the volunteers; patients completed only 1 series of swallows for no-sedation HRM.ResultsA motility diagnosis of normal motility was observed in all 12 volunteers post-sedation. Two volunteers had a diagnosis of borderline ineffective esophageal motility, one during the no-sedation-1 period and the other during the no-sedation-2 period; all of the other no-sedation HRIM studies yielded a normal motility diagnosis. Six of seven patients had the same diagnosis in both no-sedation and post-sedation HRM, including 1 distal esophageal spasm, 3 achalasia (2 type II and 1 type III), and 2 esophagogastric junction outflow obstruction. Only one patient’s HRM classification changed from ineffective esophageal motility at no-sedation to normal esophageal motility at post-sedation.ConclusionsPerforming HRIM after endoscopy with conscious sedation had minimal clinical impact on the motility diagnosis or motility parameters. Thus, this approach may be a viable alternative for patients who cannot tolerate unsedated catheter placement.

Impingement-Free Hip Flexion in Asymptomatic Young Adult Women.

Ultrasound-assisted measurement of hip flexion has demonstrated that hip flexion has been historically overestimated in men. To our knowledge, assessment of hip flexion in women using similar methods has not been reported. Establishing normative values for hip flexion is vital to aid diagnosis, management, and future research. Therefore, we asked 2 questions: (1) At what range of midsagittal hip flexion do soft-tissue impingement and femoroacetabular abutment occur in asymptomatic young adult women? (2) Do radiographic findings on a supine anteroposterior pelvic radiograph correlate with ultrasound-assisted measurements of hip flexion? Fifty-five asymptomatic adult women volunteers (107 hips) underwent ultrasound-assisted assessment of hip flexion. Hip flexion was recorded at the initiation of labral contact and at bone-on-bone contact. Recorded motion was correlated with common radiographic measurements of hip morphology as observed on a supine anteroposterior pelvic radiograph. The mean age of the subjects was 26 ± 3 years (range, 21 to 35 years), and the mean body mass index was 23 ± 3 kg/m (range, 17 to 31.6 kg/m). Mean impingement-free and maximum midsagittal passive flexion were 72° ± 8° (95% confidence interval [CI], 70° to 74°) and 101° ± 11° (95% CI, 99° to 103°), respectively. There were no significant correlations between radiographic measurements of hip morphology and ultrasound-measured hip range of motion. Observed hip flexion in the asymptomatic hips of young women is substantially less than has been historically reported. Morphologic features that are measurable on anteroposterior pelvic radiographs do not correlate with ultrasound-measured hip flexion. Diagnosis of hip disorders and treatments that are designed to alter hip range of motion should be based on normative data. Future studies regarding surgical restoration and/or preservation of hip flexion should be based on an understanding of normal hip range of motion. Ultrasound-assisted hip flexion measurement established normative values to guide surgical restoration and/or preservation of hip flexion.

Age-based normal sagittal alignment in Chinese asymptomatic adults: establishment of the relationships between pelvic incidence and other parameters.

To investigate the age-based normal values of sagittal parameters and establish the relationships between them in Chinese population. Two hundred eighteen asymptomatic adult volunteers were included in this cross-sectional study. The whole spine standing radiograph was taken from them, and the parameters including sagittal vertical axis (SVA), T1 pelvic angle (TPA), global tilt (GT), spino-sacral angle, lumbar lordosis (LL), thoracic kyphosis (TK), T1 slope (T1S), cervical lordosis (CL), C2-C7SVA, pelvic tilt (PT), sacral slop (SS) and pelvic incidence (PI) were measured. The gender differences in sagittal alignment were compared. Pearson correlation was calculated, and a linear regression analysis was used to establish the relation between PI and other parameters. The average values of PI, LL, TPA and GT were 46.2°, 48.2°, 7.8° and 10.6°, respectively, in this cohort. SVA, GT, TPA, TK, T1S, CL and PT significantly increased with age (p < 0.05). The females presented smaller T1S, C2-C7SVA and larger PI, PT than the males. The relationships between PI and TPA, GT, SS, LL could be presented as TPA = 0.411 * PI - 11.2 (R2 = 0.328, p < 0.001), GT = 0.483 * PI - 11.7 (R2 = 0.297, p < 0.001), SS = 0.354 * PI + 16.1 (R2 = 0.203, p < 0.001), LL = 0.588 * PI + 21.0 (R2 = 0.267, p < 0.001), respectively. The normal values of sagittal parameters were presented and changed with age in Chinese asymptomatic population. The gender differences existed in sagittal parameters. The relationships between PI and other parameters were established which could be used for further research. These slides can be retrieved under Electronic Supplementary Material.

177 The Presence of Clostridioides difficile Strains in the Gut by Next Generation Shotgun Sequencing: Innocent Bystander or Villain?

INTRODUCTION: Pathogenic Clostridioides difficile (C. difficile) is the most common cause of nosocomial infection in the United States. However, the prevalence of C. difficile colonization in the general population is poorly understood. We sought to determine the presence and nature of various C. difficile strains colonizing a representative sample of 17 asymptomatic adult volunteers, consisting of 10 healthy and 7 stable Crohn's patients. METHODS: Next-generation (NGS) shotgun sequencing was performed on fecal samples. Following fecal collection, DNA was extracted from stool samples, before being quantitated and normalized for downstream library fabrication utilizing shotgun methodology. Prepared and indexed libraries were subsequently pooled and sequenced on the Illumina NextSeq 550 System. Sample FASTQ files were analyzed with a computational tool (Kraken) profiling the microbial communities from metagenomic sequencing data with species level resolution. Individual microbiome profiles were then analyzed for the presence of C. difficile and specific categorical strains (Figure 1). RESULTS: All 17/17 subjects (100%) were found to possess ≥1 strain of C. difficile (Figure 1). The ATCC 43255 strain was the most common strain (94.1% 16/17), followed by QCD-63q42 (88.2% 15/17), and then M120 and QCD-37x79 strains (both identified in 10/17 [58.8%] individuals). CONCLUSION: In our representative sample of 17 adult volunteers, all (100%) were found to possess at least one C. difficile strain in their gut, with many colonized by several strains. While it is recognized that some C. difficile strains are pathogenic, our findings indicate that various non-pathogenic C. difficile species make up an important component of the commensal gut microbiome, and may perhaps play a protective role. Although symptomatic toxigenic CDI is a clear indication for therapy, C. difficile colonization with non-toxigenic strains is not believed to be a direct precursor for CDI. These findings demonstrate our need for awareness that numerous strains of C. difficile exist and the relevance of sequencing (a) prior to hospitalization or antibiotic treatment to help predict those at risk of CDI, and (b) after treatment to identify any loss of potentially protective components of our microbiome.