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Study Design: Systematic review. Objective: To assess the current literature regarding the relationship between the shoulder and the spine with regard to (1) overlapping pain pathways; (2) differentiating history, exam findings, and diagnostic findings; (3) concomitant pathology and optimal treatments; and (4) cervical spine-based etiology for shoulder problems. Methods: A systematic literature search was performed according to the guidelines set forth by the Cochrane Collaboration. Studies were included if they examined the clinical, anatomical, or physiological overlap between the shoulder and cervical spine. Two reviewers screened and selected full texts for inclusion according to the objectives of the study. Quality of evidence was graded using OCEBM (Oxford Center for Evidence Based Medicine) and MINORS (Methodological Index for Nonrandomized Studies) scores. Results: Out of 477 references screened, 76 articles were included for review and grouped into 4 main sections (overlapping pain pathways, differentiating exam findings, concomitant/masquerading pathology, and cervical spine-based etiology of shoulder pathology). There is evidence to suggest cervical spine pathology may cause shoulder pain and that shoulder pathology may cause neck pain. Specific examination tests used to differentiate shoulder and spine pathology are critical as imaging studies may be misleading. Diagnostic injections can be useful to confirm sources of pain as well as predicting the success of surgery in both the shoulder and the spine. There is limited evidence to suggest alterations in the relationship between the spine and the scapula may predispose to shoulder impingement or rotator cuff tears. Moreover, cervical neurological lesions may predispose patients to developing rotator cuff tears. The decision to proceed with shoulder or spine surgery first should be delineated with careful examination and the use of shoulder and spine diagnostic injections. Conclusion: Shoulder and spine pathology commonly overlap. Knowledge of anatomy, pain referral patterns, shoulder kinematics, and examination techniques are invaluable to the clinician in making an appropriate diagnosis and guiding treatment. In this review, we present an algorithm for the identification and treatment of shoulder and cervical spine pathology.

Study design Retrospective review of a prospectively-collected multicenter database. Objectives The objective of this study was to determine optimal strategies in terms of focal angular correction and length of proximal extension during revision for PJF. Methods 134 patients requiring proximal extension for PJF were analyzed in this study. The correlation between amount of proximal junctional angle (PJA) reduction and recurrence of proximal junctional kyphosis (PJK) and/or PJF was investigated. Following stratification by the degree of PJK correction and the numbers of levels extended proximally, rates of radiographic PJK (PJA >28° & ΔPJA >22°), and recurrent surgery for PJF were reported. Results Before revision, mean PJA was 27.6° ± 14.6°. Mean number of levels extended was 6.0 ± 3.3. Average PJA reduction was 18.8° ± 18.9°. A correlation between the degree of PJA reduction and rate of recurrent PJK was observed (r = −.222). Recurrent radiographic PJK (0%) and clinical PJF (4.5%) were rare in patients undergoing extension ≥8 levels, regardless of angular correction. Patients with small reductions (<5°) and small extensions (<4 levels) experienced moderate rates of recurrent PJK (19.1%) and PJF (9.5%). Patients with large reductions (>30°) and extensions <8 levels had the highest rate of recurrent PJK (31.8%) and PJF (16.0%). Conclusion While the degree of focal PJK correction must be determined by the treating surgeon based upon clinical goals, recurrent PJK may be minimized by limiting reduction to <30°. If larger PJA correction is required, more extensive proximal fusion constructs may mitigate recurrent PJK/PJF rates.

Study Design Reliability analysis. Objectives Vertebral pelvic angles (VPA) are gaining popularity given their ability to describe the shape of the spine. Understanding the reliability and minimal detectable change (MDC) is necessary to determine how these measurement tools should be used in the manual assessment of spine radiographs. Our aim is to assess intra- and interobserver intraclass correlation coefficients (ICC) and the MDC in the use of VPA for assessing alignment in adult spinal deformity (ASD). Methods Three independent examiners blindly measured T1, T4, T9, L1, and L4PA twice in ASD patients with a 4-week window after the initial measurements. Patients who had undergone hip or shoulder arthroplasty, fused or transitional vertebrae, or whose hip joints were not visible on radiographs were excluded. Power analysis calculated a minimum sample size of 19. Both intra- and interobserver ICC and MDC, which denotes the smallest detectable change in a true value with 95% confidence, were calculated. Results Out of the 193 patients, 39 were ultimately included in the study, and 390 measurements were performed by 3 raters. Intraobserver ICC values ranged from .90 to .99. The interobserver ICC was .97, .97, .96, .95, and .92, and the MDC was 5.3°, 5.1°, 4.8°, 4.9°, and 4.1° for T1, T4, T9, L1, and L4PA, respectively. Conclusion All VPAs showed excellent intra- and interobserver reliability, however, the MDC is relatively high compared to typical ranges for VPA values. Therefore, surgeons must be aware that substantial alignment changes may not be detected by a single VPA.

Fluorescent small molecules have become indispensable tools for biomedical research along with the rapidly developing optical imaging technology. We report here a neural stem cell specific boron-dipyrromethane (BODIPY) derivative compound of designation red 3 (CDr3), developed through a high throughput/content screening of in-house generated diversity oriented fluorescence library in stem cells at different developmental stages. This novel compound specifically detects living neural stem cells of both human and mouse origin. Furthermore, we identified its binding target by proteomic analysis as fatty acid binding protein 7 (FABP7), also known as brain lipid binding protein) which is highly expressed in neural stem cells and localized in the cytoplasm. CDr3 will be a valuable chemical tool in the study and applications of neural stem cells.

Study Design: Retrospective cohort study. Objective: Develop a simple scoring system to estimate proximal junctional kyphosis (PJK) risk. Methods: A total of 417 adult spinal deformity (ASD) patients (80% females, 57.8 years) with 2-year follow-up were included. PJK was defined as a >10° kyphotic angle between the upper-most instrumented vertebra (UIV) and the vertebrae 2 levels above the UIV (UIV+2). Based on a previous literature review, the following point score was attributed to parameters likely to impact PJK development: age >55 years (1 point), fusion to S1/ilium (1 point), UIV in the upper thoracic spine (UIV-UT: 1 point), UIV in the lower thoracic region (UIV-LT: 2 points), flattening of the thoracic kyphosis (TK) relative to the lumbar lordosis (LL; ie, ▵LL − ▵TK) greater than 10° (1 point). Results: At 2 years, the overall PJK rate was 43%. The odds ratios for each risk factor were the following: age >55 years (2.52), fusion to S1/ilium (5.17), UIV-UT (6.63), UIV-LT (8.24), and ▵LL − ▵TK >10° (1.59). Analysis by risk factor revealed a significant impact on PJK (no PJK vs PJK): age >55 years (28% vs 51%, P < .001), LIV S1/ilium (16.3% vs 51.4%, P < .001), UIV in lower thoracic spine (12.0% vs 38.7% vs 52.9%, P < .001), and a >10° surgical reduction in TK relative to LL increase (40.0% vs 51.5%, P < .001). The PJK rate by point score was as follows: 1 = 17%, 2 = 29%, 3 = 40%, 4 = 53%, and 5 = 69%. Conclusion: A pragmatic scoring system was developed that is tied to the increasing risk of PJK. These findings are helpful for surgical planning and preoperative counseling.

Study Design: Retrospective cohort study. Objective: Investigate risk factors for PJK including theoretical kyphosis, mechanical loading at the UIV and age adjusted offset alignment. Methods: 373 ASD patients (62.7 yrs ± 9.9; 81%F) with 2-year follow up and UIV of at least L1 and LIV of sacrum were included. Images of patients without PJK, with PJK and with PJF were compared using standard spinopelvic parameters before and after the application of the validated virtual alignment method which corrects for the compensatory mechanisms of PJK. Age-adjusted offset, theoretical thoracic kyphosis and mechanical loading at the UIV were then calculated and compared between groups. A subanalysis was performed based on the location of the UIV (upper thoracic (UT) vs. Lower thoracic (LT)). Results: At 2-years 172 (46.1%) had PJK, and 21 (5.6%) developed PJF. As PJK severity increased, the post-operative global alignment became more posterior secondary to increased over-correction of PT, PI-LL, and SVA (all P < 0.005). Also, a larger under correction of the theoretical TK (flattening) and a smaller bending moment at the UIV (underloading of UIV) was found. Multivariate analysis demonstrated that PI-LL and bending moment offsets from normative values were independent predictors of PJK/PJF in UT group; PT and bending moment difference were independent predictors for LT group. Conclusions: Spinopelvic over correction, under correction of TK (flattening), and under loading of the UIV (decreased bending moment) were associated with PJK and PJF. These differences are often missed when compensation for PJK is not accounted for in post-operative radiographs.

The goal of this study was to explore sex-related variations of global alignment parameters and their distinct evolution patterns across age groups. This multicentric retrospective study included healthy volunteers with full-body biplanar radiographs in free-standing position. All radiographic data were collected from 3D reconstructions: global and lower limb parameters, pelvic incidence (PI) and sacral slope (SS). Lumbar lordosis (LL), thoracic kyphosis (TK) and cervical lordosis (CL) were also assessed as well as the lumbar and thoracic apex, and thoracolumbar inflexion point. The population was divided into five 5 age groups: Children, Adolescents, Young, Middle-Aged and Seniors. This study included 861 subjects (53% females) with a mean age of 34 ± 17 years. Mean PI was 49.6 ± 11.1 and mean LL was - 57.1 ± 11.6°. Females demonstrated a PI increase between Young and Middle-Aged groups (49 ± 11° vs. 55 ± 12°, p < 0.001) while it remained stable in males. SS and LL increased with age in females while remaining constant in males between Children and Middle-aged and then significantly decreased for both sexes between Middle-Aged and Seniors. On average, lumbar apex, inflexion point, and thoracic apex were located one vertebra higher in females (p < 0.001). After skeletal maturity, males had greater TK than females (64 ± 11° vs. 60 ± 12°, p = 0.04), with significantly larger CL (-13 ± 10° vs. -8 ± 10°, p = 0.03). All global spinal parameters indicated more anterior alignment in males. Males present more anteriorly tilted spine with age mainly explained by a PI increase in females between Young and Middle-Aged, which may be attributed to childbirth. Consequently, SS and LL increased before decreasing at senior age.

We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, especially in patients with residual disease post-neoadjuvant chemotherapy. This phase II MIRINAE trial (KCSG-BR18-21) evaluates the efficacy and safety of atezolizumab combined with capecitabine versus capecitabine monotherapy as adjuvant treatment in TNBC patients with residual invasive cancer. The primary endpoint is the 5-year invasive disease-free survival (IDFS) rate. Secondary endpoints include IDFS in PD-L1 positive patients, distant relapse-free survival (DRFS), and overall survival (OS). This study addresses the limitations of KEYNOTE-522 by providing data on post-neoadjuvant therapies, potentially establishing a new standard of care for TNBC. Trial registration This trial is registered at ClinicalTrials.gov (NCT03756298).

PurposeTo investigate GAP scores in an asymptomatic cohort of adults, including older adults with age-expected changes in spinal alignment.MethodsOne hundred and twenty asymptomatic volunteers underwent full-body radiographic scans. Demographics and sagittal radiographic parameters (pelvic incidence, sacral slope, L1-S1 lordosis, L4-S1 lordosis, and global tilt) were measured and GAP scores calculated (www.gapcalculator.com). Mann–Whitney U test compared groups.ResultsEighty-five individuals (65 female, average age 48 ± 16 years, BMI 27 ± 6 kg/cm2) were analyzed. The median GAP score was that of a proportioned spine (0, range 0–10). 20% were moderately disproportioned and 6% were severely disproportioned. The mean relative pelvic version, relative lumbar lordosis (RLL), lumbar distribution index (LDI), and relative spinopelvic alignment were all considered aligned, although the mean RLL and LDI scores were both greater than 1. When categorized by age (< 60 years, ≥ 60 years), the median GAP score of the younger group was 0 (normal), while the median GAP score of the older cohort was 1 (normal) and different from the younger group (p < 0.001).ConclusionMost patients in this asymptomatic, nonoperative cohort were normally proportioned. However, a large percentage of asymptomatic volunteers were moderately or severely disproportioned. Older patients had higher scores, indicating some disproportion. There was also a small number of severely sagittally misaligned and poorly proportioned, yet asymptomatic, volunteers. Further refinement of individualized targets is needed to determine the effect on mechanical complications and quality of life given the divergent recommendations of age-adjusted targets and GAP targets.