Different Risk Factors between Bony and Ligamentous Proximal Junctional Failure in Patients Undergoing Thoracolumbar Fusion to Pelvis for Adult Spinal Deformity.

STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the risk factors for bony proximal junctional failure (B-PJF) and ligamentous PJF (L-PJF) separately after adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: Despite numerous studies about the risk factors of PJF, it remains unclear whether same risk factors can be applied to both B-PJF and L-PJF. METHODS: Patients who underwent corrective surgery from low thoracic level (T9-T12) to pelvis with minimum follow-up duration of two years were included in this study. Patients with PJF were divided into two groups according to the involvement of bony structure: B-PJF and L-PJF. The control group was created using patients who did not develop PJF for ≥2 years postoperatively (no-PJF group). Risk factors were analyzed by comparing various clinical and radiographic parameters between no PJF versus B-PJF group and between no PJF versus L-PJF groups. RESULTS: The final study cohort comprised 240 patients. The mean age was 68.7 years, and there were 205 women (85.4%). On average, 8.1 levels were fused. PJF developed in 103 patients, with 70 (68.0%) in the B-PJF group and 33 (32.0%) in the L-PJF group. Stepwise logistic regression analyses revealed that older age (odds ratio [OR]=1.088), higher body mass index (BMI) (OR=1.161), osteoporosis (OR=3.293), greater postoperative lumbar distribution index (OR=1.032), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis (OR=3.964) were significant risk factors for B-PJF. Meanwhile, no use of transverse process (TP) hook was the single risk factor for L-PJF (OR=4.724). CONCLUSIONS: Understanding the difference in risk factors between B-PJF and L-PJF will facilitate the optimization of surgical outcome for patients with ASD. Appropriate correction of sagittal malalignment along with use of TP hook is advisable to mitigate both B-PJF and L-PJF development.

Validation of Sagittal age-adjusted Score in Predicting Proximal Junctional Kyphosis/Failure and Clinical Outcomes Following Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVES: To validate the sagittal age-adjusted score (SAAS) in predicting proximal junctional kyphosis/failure (PJK/F) and good clinical outcomes following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: SAAS is a relatively new assessment system that incorporates age-adjusted sagittal parameters of pelvic incidence (PI) - lumbar lordosis (LL), pelvic tilt (PT), and T1 pelvic angle (TPA) to predict the PJK/F. External validation is required to verify its clinical usefulness. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum or pelvis. SAAS was calculated based on the scores of the three components: PI-LL, PT, and TPA. PJK/F rates and clinical outcomes were compared among the correction categories (undercorrection, matched correction, and overcorrection) for the SAAS as well as for each of the three components. PJK/F rates were compared according to the correction groups of the sagittal components and total SAAS using the chi-square test. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive ability of overcorrection to develop PJK/F for the three sagittal parameters and SAAS. PROMs at final follow-up were compared among correction groups using ANOVA with Bonferroni post-hoc corrections. RESULTS: A total 411 patients were included in the study (mean age: 69.3 y, mean body mass index: 25.9 kg/m2, total levels fused: 7.7 levels, and follow-up duration: 43.3 mo). Postoperative SAAS categories were as follow: undercorrection (13.4%), matched correction (30.2%), and overcorrection (56.4%). The PJK/F rates were significantly higher in the overcorrection group relative to PI-LL component (P=0.001) as well as SAAS (P=0.038) compared to undercorrection or matched correction groups. The clinical outcomes were best in patients who achieved matched correction relative to PI-LL component as well as SAAS compared to the other correction groups. However, the differentiating power of clinical outcomes across the correction categories was greater in the PI-LL component than in the SAAS. CONCLUSION: This study validated the efficacy of SAAS system to differentiate PJK/F development and good clinical outcomes. However, its differentiating power seems to be largely attributable to the function of the PI-LL component, as the PI-LL correction status better predicted PJK/F risk and clinical outcomes than SAAS.

Risk Factors for Recurrent Proximal Junctional Failure Following Adult Spinal Deformity Surgery: Analysis of 60 Patients Undergoing Fusion Extension Surgery for Proximal Junctional Failure.

BACKGROUND: Despite numerous studies identifying risk factors for proximal junctional failure (PJF), risk factors for recurrent PJF (R-PJF) are still not well established. Therefore, we aimed to identify the risk factors for R-PJF following adult spinal deformity (ASD) surgery. METHODS: Among 479 patients who underwent ≥5-level fusion surgery for ASD, the focus was on those who experienced R-PJF at any time or did not experience R-PJF during a follow-up duration of ≥1 year. PJF was defined as a proximal junctional angle (PJA) ≥28° plus a difference in PJA ≥22° or performance of revision surgery regardless of PJA degree. The patients were divided into 2 groups according to R-PJF development: no R-PJF and R-PJF groups. Risk factors were evaluated focusing on patient, surgical, and radiographic factors at the index surgery as well as at the revision surgery. RESULTS: Of the 60 patients in the final study cohort, 24 (40%) experienced R-PJF. Significant risk factors included greater postoperative sagittal vertical axis (OR = 1.044), overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis (PI-LL; OR = 7.794) at the index surgery, a greater total sum of the proximal junctional kyphosis severity scale (OR = 1.145), and no use of the upper instrumented vertebra cement (OR = 5.494) at the revision surgery. CONCLUSIONS: We revealed that the greater postoperative sagittal vertical axis and overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis at the index surgery, a greater proximal junctional kyphosis severity scale score, and no use of upper instrumented vertebra cement at the revision surgery were significant risk factors for R-PJF. CLINICAL RELEVANCE: To reduce the risk of R-PJF after ASD surgery, avoiding under- and overcorrection during the initial surgery is recommended. Additionally, close assessment of the severity of PJF with timely intervention is crucial, and cement augmentation should be considered during revision surgery.

Incidence and Risk Factors for Mechanical Failure after Anterior Column Realignment in Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the incidence and risk factors of mechanical failure (MF) following anterior column realignment (ACR) in patients with severe degenerative sagittal imbalance (DSI). SUMMARY OF BACKGROUND DATA: Considering the biomechanical properties of the procedure, ACR may increase the risk of MF, including proximal junctional kyphosis (PJK) and rod fracture (RF). However, this issue has been poorly documented in the literature. METHODS: We included patients aged ≥60 years with severe DSI radiographically defined by pelvic incidence (PI) - lumbar lordosis (LL) ≥20° undergoing ≥5-level fusion, including the sacrum. PJK was defined radiographically as a proximal junctional angle (PJA)>28° plus Δ PJA of>22°. RF was evaluated at ACR levels performed. Clinical and radiographic variables were compared to identify the risk factors for PJK and RF, then multivariate analysis was performed by combining PJK and RF into a single composite outcome of MF. RESULTS: We included a total of 147 patients in the final study cohort. The mean age was 70.3 years, and there were 126 women (90.6%). The median fusion length was 8 levels. After surgery, PI-LL was corrected from 48.1° to 4.3°. MF developed in 49 patients (33.3%); PJK in 41 (27.9%), RF in 11 (7.5%), and both PJK and RF in 3 (2.0%) patients. Multivariate analyses revealed that osteoporosis (odds ratio [OR]=2.361, 95% confidence interval [CI]=1.270 - 5.590, P=0.048) and an increased number of ACR levels (OR=1.762, 95% CI=1.039 - 3.587, P=0.036) were significant risk factors for MF. CONCLUSION: A considerable number of patients (33.3%) developed MF after deformity correction using ACR procedures. Therefore, appropriate surgical strategies are necessary to prevent MF in patients undergoing deformity correction using ACR, with special attention to the risk factors we identified here.

Different characteristics between acute and delayed proximal junctional failure in elderly patients undergoing corrective surgery for adult spinal deformity: comparative analysis of risk factor, failure mode, and clinical consequences.

BACKGROUND CONTEXT: While numerous studies have been conducted on proximal junctional failure (PJF), the clinical significance of acute and delayed PJF remains poorly understood. PURPOSE: The primary object of this study is to investigate the risk factors separately for acute and delayed PJF. Secondly, we aim to assess the incidence of each failure mode and their clinical consequences in relation to acute and delayed PJF. STUDY DESIGN/SETTING: Retrospective comparative study. PATIENT SAMPLE: Patients aged ≥60 years who underwent deformity correction with ≥5-level fusion to sacrum. OUTCOME MEASURES: Risk factor, failure modes, and patient-reported outcome measure (PROM). METHODS: Acute PJF is defined as PJF occurring within 6 months, while delayed PJF occurring after 6 months. Risk factors were analyzed by comparing various clinical and radiographic parameters among 3 groups: no, acute, and delayed PJF groups. The failure modes, including soft tissue failure, vertebral fracture, fixation failure, and myelopathy, were compared among these groups. The clinical subsequences after PJF development were evaluated by assessing the change in proximal junctional angle (PJA), revision rate, and patient-reported outcome measure (PROM). RESULTS: A study cohort of 363 patients was included in the analysis. Among them, 156 patients experienced PJF, with 87 patients (55.8%) in the acute PJF group and 69 patients (44.2%) in the delayed PJF group. Multivariate analyses showed that older age (Odds ratio [OR] = 1.057, 95% confidence interval [CI] = 1.002-1.118), osteoporosis (OR=2.149, 95% CI = 1.074-4.300), high American Society of Anesthesiology ASA score (OR=2.150, 95% CI = 1.089-4.245), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis target (OR=4.031, 95% CI = 1.962-8.280) were identified as risk factors for the development of acute PJF. On the other hand, a high body mass index (OR=1.150, 95% CI = 1.049-1.251) and an uppermost instrumented vertebra located at ≤T10 (OR=2.267, 95% CI = 1.205-4.268) were found to be associated with delayed occurrence of PJF. No radiographic parameters were found to be related to the development of delayed PJF. In terms of failure modes, vertebral fracture and fixation failure were more commonly observed in acute PJF, while soft tissue failure and myelopathy were more predominant in delayed PJF. The clinical course was more aggressive in the acute PJF group compared to the delayed PJF group, as evidenced by a greater increase in PJA, a higher revision rate, and worse PROM. CONCLUSIONS: This study demonstrated different risk factors between the acute and delayed PJF. It was found that overcorrection relative to the age-adjusted PI-LL target increased the risk of acute PJF, but had no impact on the development of delayed PJF. Therefore, a different surgical strategy needs to be established to mitigate both acute and delayed PJF.

Comparison of Surgical Burden, Radiographic and Clinical Outcomes According to the Severity of Baseline Sagittal Imbalance in Adult Spinal Deformity Patients.

OBJECTIVE: To determine the clinical impact of the baseline sagittal imbalance severity in patients with adult spinal deformity (ASD). METHODS: We retrospectively reviewed patients who underwent ≥ 5-level fusion including the pelvis, for ASD with a ≥ 2-year follow-up. Using the Scoliosis Research Society-Schwab classification system, patients were classified into 3 groups according to the severity of the preoperative sagittal imbalance: mild, moderate, and severe. Postoperative clinical and radiographic results were compared among the 3 groups. RESULTS: A total of 259 patients were finally included. There were 42, 62, and 155 patients in the mild, moderate, and severe groups, respectively. The perioperative surgical burden was greatest in the severe group. Postoperatively, this group also showed the largest pelvic incidence minus lumbar lordosis mismatch, suggesting a tendency towards undercorrection. No statistically significant differences were observed in proximal junctional kyphosis, proximal junctional failure, or rod fractures among the groups. Visual analogue scale for back pain and Scoliosis Research Society-22 scores were similar across groups. However, severe group's last follow-up Oswestry Disability Index (ODI) scores significantly lower than those of the severe group. CONCLUSION: Patients with severe sagittal imbalance were treated with more invasive surgical methods along with increased the perioperative surgical burden. All patients exhibited significant radiological and clinical improvements after surgery. However, regarding ODI, the severe group demonstrated slightly worse clinical outcomes than the other groups, probably due to relatively higher proportion of undercorrection. Therefore, more rigorous correction is necessary to achieve optimal sagittal alignment specifically in patients with severe baseline sagittal imbalance.

The Optimal Lowest Instrumented Vertebra to Prevent the Distal Adding-On Phenomenon in Patients Undergoing Selective Thoracic Fusion for Adolescent Idiopathic Scoliosis with Lenke Type 1A and 1B Curves: Comparison of Nine Selection Criteria.

Background/Objectives: There is no solid consensus regarding which lowest instrumented vertebra (LIV) selection criterion is best to prevent distal adding-on (DA) after adolescent idiopathic scoliosis (AIS) surgery. This study aims to search out the LIV selection criteria in the literature and to compare the ability of each LIV selection criterion to prevent DA in patients with AIS. Methods: Patients who underwent thoracic fusion for AIS of Lenke type 1A or 1B were included in this study. Nine criteria for LIV selection were found in a literature review. For each patient, whether the postoperative actual location of LIV was met with the suggested locations of the LIV was assessed. The preventive ability of nine criteria against DA was evaluated using logistic regression analysis. The patients who met the LIV selection criteria but developed DA were investigated. Results: The study cohort consisted of 145 consecutive patients with a mean age of 14.8 years. The criteria of Suk (OR = 0.267), Parisini (OR = 0.230), Wang (OR = 0.289), and Qin (OR = 0.210) showed a significantly decreased risk of DA if the LIV selection criterion was chosen at each suggested landmark. As the additional levels were fused, there was no statistically significant benefit in further reducing the risk of DA. Among the patients who met each criterion, the incidence of DA was lower in criteria by Takahashi (5.9%), Qin (7.1%), and King (7.4%) than the others. Conclusions: Qin's criterion, using the substantially touching vertebra concept, has the highest preventive ability against DA development. Extending the instrumentation further distal to this suggested LIV criterion did not add further benefit.

Are Surgical Outcomes Different According to Baseline Balance Status in Elderly Patients with Degenerative Sagittal Imbalance?

STUDY DESIGN: Retrospective study. OBJECTIVE: We sought to compare surgical outcomes according to baseline balance statuses in elderly patients with degenerative sagittal imbalance (DSI). SUMMARY OF BACKGROUND: Although optimal sagittal correction has been emphasized for good surgical outcomes, the effect of the state of preoperative balance on surgical outcome has been adequately described at present. METHODS: Patients aged ≥60 years with DSI who underwent ≥5-level fusion to the sacrum were included. Among them, only those who postoperatively achieved the optimal age-adjusted pelvic incidence (PI) - lumbar lordosis (LL) target were included in this study. Study participants were divided into two groups according to their preoperative sagittal vertical axis (SVA): compensatory balance (SVA <5 cm, group CB) and decompensation (SVA ≥5 cm, group D). Comparisons between the two groups were performed using the chi-squared test or Fisher's exact test for categorical variables and the independent t- test or Wilcoxon rank- sum test for continuous variables. RESULTS: A total of 156 patients whose postoperative sagittal alignment matched the age-adjusted PI-LL target constituted the study cohort. There were 59 patients in group CB and 97 patients in group D. Mean follow-up duration was 50.0 months after surgery. Immediate postoperatively, sacral slope and SVA were significantly greater in group D than in group CB. At last follow-up, the SVA was significantly greater in group D than in group CB (43.6 vs. 22.7 mm), while no significant differences were found in other sagittal parameters. The Oswestry disability index and Scoliosis Research Society -22 scores at the last follow-up were significantly worse in group D than in group CB. CONCLUSION: The SVA tended to experience less correction postoperatively, with evidence of further deterioration during follow-up in group D than in group CB. This suboptimal correction of SVA may contribute to the inferior clinical outcomes encountered in group D relative to group CB. Therefore, we recommend correction of PI-LL as close as possible to the lower limit of the suggested PI-LL target range in patients with evidence of preoperative decompensation.

Ideal Lumbar Lordosis Correction in Patients with Adult Spinal Deformity Without Adversely Impacting Pelvic Tilt and Pelvic Incidence Minus Lumbar Lordosis: A Study of 426 Cases.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the ideal pelvic incidence (PI) - lumbar lordosis (LL) range to prevent pelvic tilt (PT) undercorrection while avoiding PI-LL overcorrection following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND: PI-LL and PT are the important sagittal parameters to be restored to an adequate range by surgery. Ideal PI-LL target without causing PI-LL overcorrection and PT undercorrection has not been documented. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum. Receiver operating characteristic (ROC) curve analysis was performed to calculate the lower limit of the ideal PI-LL without causing PI-LL overcorrection and the upper limit of ideal PI-LL without causing PT undercorrection. The calculated ideal PI-LL was validated in terms of proximal junctional kyphosis and failure (PJK and PJF) rates and clinical outcomes. Analyses were performed according to age subgroups (<70 and ≥70 y). RESULTS: In total, 426 patients were included in the study. Female patients were predominant (85.4%), with a mean age of 69.8 years. The lower limits of PI-LL were calculated as 4.9° for all patients, 2.3° for patients aged <70 years, and 7.9° for patients aged ≥70 years. Meanwhile, the upper limits of PI-LL were calculated as 12.7° for all patients, 12.5° for patients aged <70 years, and 13.3° for patients aged ≥70 years. There were no significant differences in the PJK and PJF rates among the new three PI-LL groups. Clinical outcomes were significantly better in patients with the ideal PI-LL group than those in patients with overcorrection or undercorrection groups for all age groups. CONCLUSION: The ideal PI-LL correction target without adversely impacting PT and PI-LL was calculated at 2.3°-12.5° for patients aged <70 years and 7.9°-13.3° for patients aged ≥70 years. These guideline parameters may help ensure optimal clinical outcomes without increasing the risk of PJK/F.

Hook Fixation at Uppermost Instrumented Vertebra +1 Reduced Proximal Junctional Failure in Adult Patients With Spinal Deformity Having Achieved Optimal Deformity Correction by Sagittal Age-Adjusted Score.

BACKGROUND AND OBJECTIVES: Appropriate correction relative to the age-adjusted sagittal alignment target reduces the proximal junctional failure (PJF) risk. Nonetheless, a considerable number of patients suffer from PJF despite optimal correction. The aim of this study was to identify the risk factors of PJF that occurs despite optimal correction relative to the sagittal age-adjusted score (SAAS) in adult spinal deformity surgery. METHODS: Patients aged 60 years or older with adult spinal deformity who underwent ≥5-level fusion to the sacrum were initially screened. Among them, only patients who achieved optimal sagittal correction relative to the SAAS were included in the study. Optimal correction was defined as the SAAS point between -1 and +1. Various clinical and radiographic factors were compared between the PJF and no PJF groups and were further evaluated using multivariate analysis. RESULTS: The final study cohort comprised 127 patients. The mean age was 67 years, and there were 111 women (87.4%). A mean of total fusion length was 7.2. PJF occurred in 42 patients (33.1%), while 85 patients (66.9%) did not develop PJF. Multivariate analysis showed that a high body mass index (odds ratio [OR] = 1.153, 95% CI = 1.027-1.295, P = .016), a higher lordosis distribution index (LDI) (OR = 1.024, 95% CI = 1.003-1.045, P = .022), and no use of hook fixation (OR = 9.708, 95% CI = 1.121-76.923, P = .032) were significant risk factors of PJF development. In the receiver operating characteristic curve analysis, the cutoff value for the LDI was calculated as 61.0% (area under the curve = 0.790, P < .001). CONCLUSION: PJF developed in a considerable portion of patients despite optimal correction relative to the age-adjusted alignment. The risk factors of PJF in this patient group were high body mass index, high LDI exceeding 61%, and no use of hook fixation. PJF could be further decreased by properly managing these risk factors along with optimal sagittal correction.

Reliability and Validity of the Korean version of the Center for Neurologic Study Bulbar Function Scale (K-CNS-BFS): An observational study.

Bulbar dysfunction in amyotrophic lateral sclerosis (ALS) significantly affects daily life, leading to weight loss and reduced survival. Methods for evaluating bulbar dysfunction, including videofluoroscopic swallowing studies and the bulbar component of the ALS Functional Rating Scale-Revised (ALSFRS-R), have been employed; however, Korean-specific tools are lacking. The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) comprehensively evaluates bulbar symptoms. This study aimed to develop and validate the Korean version of the CNS-BFS (K-CNS-BFS) to assess bulbar dysfunction in Korean patients with ALS. Twenty-seven patients with ALS were recruited from a tertiary hospital in South Korea based on revised El Escorial criteria. Demographic, clinical, and measurement data were collected. The K-CNS-BFS was evaluated for reliability and validity. Reliability assessment revealed strong internal consistency (Cronbach alpha) for the K-CNS-BFS subscales and total score. Test-retest reliability showed significant correlation. Content validity index was excellent, and convergent validity demonstrated significant correlations between the K-CNS-BFS and relevant measures. Discriminant validity was observed between the K-CNS-BFS and motor/respiratory subscores of the ALSFRS-R. Construct validity demonstrated significant correlations between the K-CNS-BFS subscales and total score. This is the first study to investigate the reliability and validity of the Korean version of the CNS-BFS, which showed consistent and reliable scores that correlated with tests for bulbar or general dysfunction. The K-CNS-BFS effectively measured bulbar dysfunction similar to the original CNS-BFS. The K-CNS-BFS is a reliable and valid tool for assessing bulbar dysfunction in patients with ALS in South Korea.

Outcomes of Hybrid Total Hip Arthroplasty for Subchondral Insufficiency Fracture of the Femoral Head.

Background: The purpose of this study was to evaluate functional outcomes, radiologic results, and complications after hybrid total hip arthroplasty (THA) in patients with subchondral insufficiency fractures (SIFs) of the femoral head. Methods: From June 2009 to December 2020, among 985 patients who underwent hybrid THA at our hospital, 19 patients diagnosed with SIF through a retrospective chart review were included. Those under 50 years of age, with radiographic findings of osteonecrosis on the contralateral side of surgery, a history of organ transplantation, and alcohol abuse, were excluded. Functional evaluation was performed using a modified Harris Hip Score (HHS). After surgery, inclination and anteversion of the acetabular cup and version of the femoral system were measured using postoperative x-ray. The outpatient follow-up was performed at 6 weeks, 3 months, 9 months, and 12 months after surgery and every year thereafter. Complications including dislocation, implant loosening, stem subsidence, and periprosthetic infection were observed on follow-up radiographs. Results: The average follow-up time was 29.3 ± 9.1 months (range, 24-64 months) with no loss to follow-up. The mean modified HHS was 83.4 ± 9.6 (range, 65-100) at the last outpatient clinic follow-up. The average inclination of the acetabular cup was 41.9° ± 3.4° (range, 37°-48°), and the anteversion was 27.5° ± 6.7° (range, 18°-39°). The version of the femoral stem was 19° ± 5.7° (range, 12°-29°). There was no case of intraoperative fracture. There were no cases of dislocation, loosening of the cup, subsidence of the femoral stem, intraoperative or periprosthetic fracture, or periprosthetic infection on the follow-up radiographs. Conclusions: In our study, hybrid THA showed favorable outcomes in patients diagnosed with SIF, and there were no further special considerations as for THA performed due to other diseases or fractures.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Label-Free Interference Imaging of Intracellular Trafficking.

Intracellular cargo trafficking is a highly regulated process responsible for transporting vital cellular components to their designated destinations. This intricate journey has been a central focus of cellular biology for many years. Early investigations leaned heavily on biochemical and genetic approaches, offering valuable insight into molecular mechanisms of cellular trafficking. However, while informative, these methods lack the capacity to capture the dynamic nature of intracellular trafficking. The advent of fluorescent protein tagging techniques transformed our ability to monitor the complete lifecycle of intracellular cargos, advancing our understanding. Yet, a central question remains: How do these cargos manage to navigate through traffic challenges, such as congestion, within the crowded cellular environment? Fluorescence-based imaging, though valuable, has inherent limitations when it comes to addressing the aforementioned question. It is prone to photobleaching, making long-term live-cell imaging challenging. Furthermore, they render unlabeled cellular constituents invisible, thereby missing critical environmental information. Notably, the unlabeled majority likely exerts a significant influence on the observed behavior of labeled molecules. These considerations underscore the necessity of developing complementary label-free imaging methods to overcome the limitations of fluorescence imaging or to integrate them synergistically.In this Account, we outline how label-free interference-based imaging has the potential to revolutionize the study of intracellular traffic by offering unprecedented levels of detail. We begin with a brief introduction to our previous findings in live-cell research enabled by interferometric scattering (iSCAT) microscopy, showcasing its aptitude and adeptness in elucidating intricate nanoscale intracellular structures. As we delved deeper into our exploration, we succeeded in the label-free visualization of the entire lifespan of nanoscale protein complexes known as nascent adhesions (NAs) and the dynamic events associated with adhesions within living cells. Our continuous efforts have led to the development of Dynamic Scattering-particle Localization Interference Microscopy (DySLIM), a generalized concept of cargo-localization iSCAT (CL-iSCAT). This label-free, high-speed imaging method, armed with iSCAT detection sensitivity, empowers us to capture quantitative and biophysical insights into cargo transport, providing a realistic view of the intricate nanoscale logistics occurring within living cells. Our in vivo studies demonstrate that intracellular cargos regularly contend with substantial traffic within the crowded cellular environment. Simultaneously, they employ inherent strategies for efficient cargo transport, such as collective migration and hitchhiking, to enhance overall transport rates─intriguingly paralleling the principle and practice of urban traffic management. We also highlight the synergistic benefits of combining DySLIM with chemical-selective fluorescent methods. This Account concludes with a "Conclusions and Outlook" section, outlining promising directions for future research and developments, with a particular emphasis on the functional application of iSCAT live-cell imaging. We aim to inspire further investigation into the efficient transport strategies employed by cells to surmount transportation challenges, shedding light on their significance in cellular phenomena.

The positive impact of smoking cessation on fracture risk in a nationwide cohort study.

Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009-2010 who had a previous health checkup 4-year prior (2005-2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807-0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917-0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture.

Highly Selective and Reversible Detection of Simulated Breath Hydrogen Sulfide Using Fe-Doped CuO Hollow Spheres: Enhanced Surface Redox Reaction by Multi-Valent Catalysts.

The precise and reversible detection of hydrogen sulfide (H2S) at high humidity condition, a malodorous and harmful volatile sulfur compound, is essential for the self-assessment of oral diseases, halitosis, and asthma. However, the selective and reversible detection of trace concentrations of H2S (≈0.1 ppm) in high humidity conditions (exhaled breath) is challenging because of irreversible H2S adsorption/desorption at the surface of chemiresistors. The study reports the synthesis of Fe-doped CuO hollow spheres as H2S gas-sensing materials via spray pyrolysis. 4 at.% of Fe-doped CuO hollow spheres exhibit high selectivity (response ratio ≥ 34.4) over interference gas (ethanol, 1 ppm) and reversible sensing characteristics (100% recovery) to 0.1 ppm of H2S under high humidity (relative humidity 80%) at 175 °C. The effect of multi-valent transition metal ion doping into CuO on sensor reversibility is confirmed through the enhancement of recovery kinetics by doping 4 at.% of Ti- or Nb ions into CuO sensors. Mechanistic details of these excellent H2S sensing characteristics are also investigated by analyzing the redox reactions and the catalytic activity change of the Fe-doped CuO sensing materials. The selective and reversible detection of H2S using the Fe-doped CuO sensor suggested in this work opens a new possibility for halitosis self-monitoring.

Biomarkers in allergen immunotherapy: Focus on eosinophilic inflammation.

Asthma and allergic rhinitis (AR) are 2 of the most common chronic inflammatory disorders and they appear to be on the rise. Current pharmacotherapy effectively controls symptoms but does not alter the underlying pathophysiology. Allergen immunotherapy (AIT) is an evidence-based therapy for asthma and AR and has been recognized as the only therapeutic method that actually modifies the allergic disease process. There is a lack of objective markers that accurately and reliably reflect the therapeutic benefits of AIT. A biomarker indicating patients that would benefit most from AIT would be invaluable. Eosinophilic inflammation is a cardinal feature of many allergic diseases. Biomarkers that accurately reflect this inflammation are needed to better diagnose, treat, and monitor patients with allergic disorders. This review examines the current literature regarding AIT's effects on eosinophilic inflammation and biomarkers that may be used to determine the extent of these effects.

Efficacy of leuprorelin in spinal and bulbar muscular atrophy: a 3-year observational study.

OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.

Risk factors of adjacent-segment disease after short-segment fusion in patients with de novo degenerative lumbar scoliosis.

OBJECTIVE: Short-segment fusion (SSF) is an effective surgical option for appropriately selected patients with de novo degenerative lumbar scoliosis (DNDLS). Considering that DNDLS is frequently accompanied by multisegment degeneration and potential instability across the entire lumbar segments, it is inevitable that unhealthy segments remain after SSF, thereby increasing the potential risk of adjacent-segment disease (ASD) occurrence. Therefore, the authors aimed to identify the risk factors for ASD in patients with DNDLS who underwent SSF. METHODS: This retrospective study included 80 patients with DNDLS (Cobb angle > 10°) who underwent SSF (1 or 2 levels) between December 2010 and July 2018 with a minimum follow-up duration of 5 years. The participants were divided into two groups: ASD and non-ASD. ASD was defined as clinical ASD rather than radiographic ASD. Various patient and operative variables were compared between the groups. Global and regional radiographic parameters (preoperatively and postoperatively) were also compared between the two groups using plain radiography and MRI. Consequently, univariate and multivariate analyses were conducted to identify the risk factors for ASD occurrence. The receiver operating characteristic (ROC) curve was used to calculate the cutoff values. RESULTS: The mean ± SD age was 67.7 ± 7.2 years at the time of SSF, and there were 62 women (77.5%) enrolled in the study. Thirty patients (37.5%) were in the ASD group and 50 patients (62.5%) were in the non-ASD group. The mean time from the surgery to ASD diagnosis was 34.9 ± 28.2 months in ASD group. Thirteen patients required revision surgery at a mean time of 8.8 ± 7.0 months after ASD occurrence. Multivariate logistic regression analysis demonstrated that preoperative disc wedging angle (OR 1.806, 95% CI 1.255-2.598, p = 0.001), presence of facet tropism (defined as ≥ 10° difference between the facet joint angles of the right and left sides) (OR 5.534, 95% CI 1.528-20.040, p = 0.009), and foraminal stenosis ≥ grade 2 (OR 5.935, 95% CI 1.253-28.117, p = 0.025) were significant risk factors for ASD development. The cutoff value of the preoperative disc wedging angle was calculated to be 2.5° using the ROC curve. CONCLUSIONS: Preoperative disc wedging angle ≥ 2.5°, presence of facet tropism, and foraminal stenosis ≥ grade 2 were identified as significant risk factors for ASD development after SSF in patients with DNDLS.

Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.