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Benjamin H Kaffenberger,1 Thomas M Kaffenberger,2 Henry K Wong1 1College of Medicine, Ohio State University, Columbus, OH, USA; 2German Cancer Research Center (DKFZ), Heidelberg, Germany Abstract: The treatment of psoriasis has been revolutionized since the introduction of biologic therapies. Prior to their introduction, it was unclear if psoriasis was primarily a keratinocyte signaling dysfunction or an autoimmune T-cell mediated pathway. Nonspecific T-cell targeting treatments had been used with some success, but they were limited by a narrow therapeutic index. The nonspecific nature of these agents was fraught with side effects, and the efficacy of these treatments pales in comparison to current treatments. The initial biologic molecules, alefacept and efalizumab, were not specific for any T-cell driven pathway, and neither are currently available in the USA. The successors to these early therapies have shown high efficacy and low side effects in psoriasis and other autoimmune diseases through the specific targeting of tumor necrosis factor-alpha (TNF-α). Since the initial use of antitumor necrosis factor agents, a renaissance in our understanding of psoriasis has been underway, leading to the elucidation of the T-helper 17 (Th17) from the Th1 pathway. With each new treatment, the pathogenesis for psoriasis continues to be more defined, allowing for improved targeted therapies and the ability to achieve new milestones in efficacy. Keywords: psoriasis vulgaris, pathophysiology, immunology, T-cell signaling, biologic therapies, psoriasis treatment

Marcus Ang1,2, Jodhbir S Mehta1–4, Arundhati Anshu1,2, Hon Kiat Wong5, Hla M Htoon2, Donald Tan1–31Singapore National Eye Centre, 2Singapore Eye Research Institute, 3Department of Ophthalmology, National University Health Systems, 4Department of Clinical Sciences, Duke-NUS Graduate Medical School, 5Department of Ophthalmology, Tan Tock Seng Hospital, SingaporeBackground: The purpose of this study was to compare endothelial cell counts after Descemet’s stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty in Asian eyes.Methods: This was a retrospective study of patients from our prospective Singapore Corneal Transplant Study cohort who received corneal transplantation in 2006–2008. We compared eyes that underwent DSAEK or penetrating keratoplasty for Fuchs’ endothelial dystrophy or pseudophakic and aphakic bullous keratopathy. Clinical data, and donor and recipient characteristics were recorded. Of 241 patients who met our inclusion criteria, 68 underwent DSAEK and 173 underwent penetrating keratoplasty. The main outcome measure was endothelial cell loss at 1 year. Secondary outcome measures were graft survival and visual outcomes at 1-year follow-up.Results: There were no significant differences in baseline characteristics of patients between the treatment groups. Percent endothelial cell loss at 1-year follow-up was greater in penetrating keratoplasty eyes (40.9% ± 2.9%) compared with DSAEK eyes (22.4% ± 2.3%; P < 0.001). DSAEK-treated eyes had significantly superior uncorrected visual acuity (mean difference = 0.42 ± 0.0059; P < 0.001) and best spectacle-corrected visual acuity (mean difference = 0.14 ± 0.032; P < 0.001) as compared with penetrating keratoplasty-treated eyes. Penetrating keratoplasty-treated eyes had worse astigmatism as compared with DSAEK-treated eyes (-3.0 ± 2.1 versus -1.7 ± 0.8; P < 0.001). Graft survival at 1 year was comparable in both groups, ie, 66/68 (97.0%) DSAEK-treated eyes versus 158/173 (92.0%) of penetrating keratoplasty-treated eyes had clear grafts (P = 0.479).Conclusion: We report lower percent endothelial cell loss comparing DSAEK and penetrating keratoplasty at 1-year follow-up in Asian eyes, with comparable graft survival rates in both groups.Keywords: Descemet’s stripping automated endothelial keratoplasty, endothelial cell count, penetrating keratoplasty

Delusional disorders often amaze psychiatrists with their variety of themes. Folie a deux is usually characterised as a shared psychotic or induced delusional disorder between two or more persons in close proximity. It has often been cited in case reports but has not been dealt with in much detail compared with other psychiatric conditions, and folie a trois has had even less attention. Only a small percentage of reported cases involve families and an even smaller fraction of these involve siblings. We hereby describe and discuss a case of folie a famille involving 3 unmarried sisters living together in isolation. This demonstrates how the one sister, who had schizophrenia, induced the other sisters to share the same delusional beliefs. We managed to separate the secondary cases using hospitalisation and medications and achieved improvement and recovery. [ABSTRACT FROM AUTHOR]

Study Design: Cross-sectional Cohort Study., Objective: To determine the cervicothoracic inflection point in an asymptomatic, adult population., Introduction: The cervicothoracic inflection point (CTIP) is an important sagittal marker to understand for patients with cervical deformities. We aimed to identify the CTIP and understand the relationship to other sagittal alignment markers., Methods: 468 adult asymptomatic volunteers (18-80 years) from 5 countries (United States, France, Japan, Singapore, Tunisia). All volunteers underwent standing full body, low dose stereo radiographs. The CTIP was identified by measuring the cervical sagittal angle (CSA) and thoracic kyphosis maximum angle (TK Max ), using the end vertebra concept. The CTIP was defined as the vertebra or disc between the lower end vertebra of the CSA and upper end vertebra of TK Max . A correlation matrix was utilized to identify the relationship between the CTIP and spinopelvic sagittal parameters of interest., Results: The most common CTIP value was the T1 vertebra. CTIPs ranged from C5 to T4, respectively. CTIP showed a weak positive correlation to age (r = 0.10, P = 0.03) and negative correlation to BMI (r = -0.11, P = 0.04). Additionally, CTIP had a minor positive correlation with OC2-CL, C7 slope, T1 slope, T1PA, T1-T12 TK, and T4-T12 TK, all statistically significant. Linear regression demonstrated increased cervical lordosis and increased TK was associated with more caudal CTIP segments., Conclusion: CTIP segments ranged from C5 to T4, with the most common segment being T1. Understanding the relationship of the CTIP to other sagittal variables is critical to patients with CD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Shoulder pain and disability from rotator cuff tears remain challenging clinical problem despite advancements in surgical techniques and materials. To advance our understanding of injury progression and develop effective therapeutics using tissue engineering and regenerative medicine approaches, it is crucial to develop and utilize animal models that closely resemble the anatomy and display the pathophysiology of the human rotator cuff. Among various animal models, the rabbit shoulder defect model is particularly favored due to its similarity to human rotator cuff pathology. However, a standardized protocol for creating a massive rotator cuff defect in the rabbits is not well defined. Therefore, the objective of our study was to establish a robust and reproducible model of a rotator cuff defect to evaluate the regenerative efficacy of scaffolds., Results: In our study, we successfully developed a rabbit model with a massive supraspinatus tendon defect that closely resembles the common rotator cuff injuries observed in humans. This defect involved a complete transection of the tendon, spanning 10 mm in length and encompassing its full thickness and width. To ensure stable scaffolding, we employed an innovative bridging suture technique that utilized a modified Mason-Allen suture as a structural support. Moreover, to assess the therapeutic effectiveness of the model, we utilized different scaffolds, including a bovine tendon extracellular matrix (ECM) scaffold and a commercial acellular dermal matrix (ADM) scaffold. Throughout the observation period, no scaffold damage was observed. Notably, comprehensive histological analysis demonstrated that the regenerative tissue in the tendon ECM scaffold group exhibited an organized and aligned fiber structure, indicating tendon-like tissue regeneration while the tissue in the ADM group showed comparatively less organization., Conclusions: This study presents a comprehensive description of the implemented procedures for the development of a highly reproducible animal model that induces massive segmental defects in rotator cuff tendons. This protocol can be universally implemented with alternative scaffolds to investigate extensive tendon defects and evaluate the efficacy of regenerative treatments. The application of our animal model offers a standardized and reproducible platform, enabling researchers to systematically evaluate, compare, and optimize scaffold designs. This approach holds significant importance in advancing the development of tissue engineering strategies for effectively repairing extensive tendon defects., (© 2024. The Author(s).)

Study Design: Single centre, cross-sectional study., Objectives: The objective is to report the prevalence of spondylolisthesis and retrolisthesis, analyse both conditions in terms of the affected levels and severity, as well as identify their risk factors., Methods: A review of clinical data and radiographic images of consecutive spine patients seen in outpatient clinics over a 1-month period is performed. Images are obtained using the EOS® technology under standardised protocol, and radiographic measurements were performed by 2 independent, blinded spine surgeons. The prevalence of both conditions were shown and categorised based on the spinal level involvement and severity. Associated risk factors were identified., Results: A total of 256 subjects (46.1% males) with 2304 discs from T9/10 to L5/S1 were studied. Their mean age was 52.2(± 18.7) years. The overall prevalence of spondylolisthesis and retrolisthesis was 25.9% and 17.1% respectively. Spondylolisthesis occurs frequently at L4/5(16.3%), and retrolisthesis at L3/4(6.8%). Majority of the patients with spondylolisthesis had a Grade I slip (84.3%), while those with retrolisthesis had a Grade I slip. The presence of spondylolisthesis was found associated with increased age ( P < .001), female gender (OR: 2.310; P = .005), predominantly sitting occupations (OR:2.421; P = .008), higher American Society of Anaesthesiology grades ( P = .001), and lower limb radiculopathy (OR: 2.175; P = .007). Patients with spondylolisthesis had larger Pelvic Incidence ( P < .001), Pelvic Tilt ( P < .001) and Knee alignment angle ( P = .011), but smaller Thoracolumbar junctional angle ( P = .008), Spinocoxa angle ( P = .007). Retrolisthesis was associated with a larger Thoracolumbar junctional angle ( P =.039)., Conclusion: This is the first study that details the prevalence of spondylolisthesis and retrolisthesis simultaneously, using the EOS technology and updated sagittal radiographic parameters. It allows better understanding of both conditions, their mutual relationship, and associated clinical and radiographic risk factors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Cross-sectional cohort study., Objective: To classify spinal morphology using the "current" and "theoretical" Roussouly systems and assess sagittal alignment in an asymptomatic cohort., Methods: 467 asymptomatic volunteers were recruited from 5 countries. Radiographic parameters were measured via the EOS imaging system. "Current" and "theoretical" Roussouly classification was assigned with sagittal whole spine imaging using sacral slope (SS), pelvic incidence (PI), and the lumbar apex. One-way analysis of variance (ANOVA) was performed to compare subject characteristics across Roussouly types, followed by post hoc Bonferroni correction., Results: Volunteers were categorized into 4 groups (Types 1-4) and 1 subgroup (Type 3 AP) using the "current" and "theoretical" Roussouly systems. The mean PI in "current" Roussouly groups was 40.8° (Type 1), 43.6° (Type 2), 52.4° (Type 3), 62.4° (Type 4), and 43.7° (Type 3AP). The mean PI in "theoretical" Roussouly groups was 36.5° (Type 1), 39.1°(Type 2), 52.5° (Type 3), 67.3° (Type 4), and 51.0° (Type 3AP). The difference in PI between "current" and "theoretical" Roussouly types was significant for Type 1 ( P = .02), Type 2 ( P < .001), Type 4 ( P < .001), and Type 3AP ( P < .001). 34.7% of subjects had a "current" Roussouly type different from the "theoretical" type. Type 3 theoretical shape had the most frequent mismatch, constituting 61.1% of the mismatched subjects. 51.5% of mismatched Type 3 become "current" Type 4., Conclusion: The distribution of Roussouly types differs depending on whether the "current" or "theoretical" classification are employed. A sizeable proportion of volunteers exhibited current and theoretical type mismatch, highlighting the need to interpret sagittal alignment cautiously when utilizing the Roussouly system., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Men and women are known to show differences in the incidence and clinical manifestations of mood and anxiety disorders. Many imaging studies have investigated the neural correlates of sex differences in emotion processing. However, it remains unclear how anxiety might impact emotion processing differently in men and women., Method: We recruited 119 healthy adults and assessed their levels of anxiety using State-Trait Anxiety Inventory (STAI) State score. With functional magnetic resonance imaging (fMRI), we examined regional responses to negative vs. neutral (Neg-Neu) picture matching in the Hariri task. Behavioral data were analyzed using regression and repeated-measures analysis of covariance with age as a covariate, and fMRI data were analyzed using a full-factorial model with sex as a factor and age as a covariate., Results: Men and women did not differ in STAI score, or accuracy rate or reaction time (RT) (Neg-Neu). However, STAI scores correlated positively with RT (Neg-Neu) in women but not in men. Additionally, in women, STAI score correlated positively with lingual gyrus (LG) and negatively with medial prefrontal cortex (mPFC) and superior frontal gyrus (SFG) activity during Neg vs. Neu trials. The parameter estimates (βs) of mPFC also correlated with RT (Neg-Neu) in women but not in men. Generalized psychophysiological interaction (gPPI) analysis in women revealed mPFC connectivity with the right inferior frontal gyrus, right SFG, and left parahippocampal gyrus during Neg vs. Neu trials in positive correlation with both STAI score and RT (Neg-Neu). In a mediation analysis, mPFC gPPI but not mPFC activity fully mediated the association between STAI scores and RT (Neg-Neu)., Conclusion: With anxiety affecting the behavioral and neural responses to negative emotions in women but not in men and considering the known roles of the mPFC in emotion regulation, we discussed heightened sensitivity and regulatory demands during negative emotion processing as neurobehavioral markers of anxiety in women., (© 2024. The Author(s).)

The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of mucosal immunity is less clear. Here, we analyzed kinetic and functional properties of anti-SARS-CoV-2 Abs in the saliva after vaccination with BNT162b2. We analyzed a total of 24 healthy donors longitudinally for up to 16 months. We found that specific IgG appeared in the saliva after the second vaccination, declined thereafter and reappeared after the third vaccination. Adjusting serum and saliva for the same IgG concentration revealed a strong correlation between the reactivity in these two compartments. Reactivity to VoCs correlated strongly as seen by ELISAs against RBD variants and by live-virus neutralizing assays against replication-competent viruses. For further functional analysis, we purified IgG and IgA from serum and saliva. In vaccinated donors we found neutralizing activity towards authentic virus in the IgG, but not in the IgA fraction of the saliva. In contrast, IgA with neutralizing activity appeared in the saliva only after breakthrough infection. In serum, we found neutralizing activity in both the IgA and IgG fractions. Together, we show that intramuscular mRNA vaccination transiently induces a mucosal immunity that is mediated by IgG and thus differs from the mucosal immunity after infection. Waning of specific mucosal IgG might be linked to susceptibility for breakthrough infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Winklmeier, Rübsamen, Özdemir, Wratil, Lupoli, Stern, Schneider, Eisenhut, Ho, Wong, Taskin, Petry, Weigand, Eichhorn, Foesel, Mader, Keppler, Kümpfel and Meinl.)

Although it is generally accepted that face recognition relies on holistic processing, it has been suggested that the simultaneous face matching task may depend on a more analytical or featural processing approach. However, empirical evidence supporting this claim is limited. In two experiments, we further explored the role of holistic and featural processing on simultaneous face matching by manipulating holistic processing through inversion and presenting faces with or without face masks. The results from Experiment 1 revealed that both inversion and face masks impaired matching performance. However, while the inversion effect was evident in both full-view and masked faces, the mask effect was only found in upright, but not inverted, faces. These results were replicated in Experiment 2 but, the inversion and mask effects were stronger in delayed face matching than in simultaneous face matching. Our findings suggest that simultaneous face matching relies on holistic processing, but to a smaller extent compared to higher memory-demanding identification tasks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Estudillo, Wong. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Surgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore., Methods: This is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 - 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups., Results: There was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p<0.001) and Separation surgery (p<0.001). There was also a significant decrease in mean blood loss (1061ml vs 664 ml vs 594ml) (p<0.001) and total transfusion (562ml vs 349ml vs 239ml) (p<0.001). Group 3 patients were more likely to have improved or normal neurology (p=<0.001) and independent ambulatory status(p=0.012). There was no significant change in overall survival., Conclusion: There has been a significant change in our surgical practice with decreased blood loss, transfusion and improved neurological and functional outcomes. Patients should be managed in a multidisciplinary manner and surgical treatment should be recommended when indicated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Hallinan, Lee, Chan, Tan, Ang, Tan, Tan, Sin, Hey, Lau, Thambiah, Wong, Liu and Kumar.)

Introduction: The role of quantitative target setting has become an important topic in debates on the improvement of road safety performance. Specifically, there are questions regarding the relationship between quantitative safety targets and their actual effects. Although previous studies have provided important insights into this subject, their empirical findings have largely been equivocal, and research on this topic remains inadequate., Methods: Based on panel data representing 20 years of observations from 34 OECD member states, we employed nonlinear and linear panel models to investigate whether and how the attributes of quantitative road safety targets (i.e., target ambition and duration) influence their success (i.e., target completion status and rate)., Results: The results indicate that a quantitative target with a higher level of ambition is associated with a lower likelihood and rate of completion, whereas there is no support for a connection between target duration and final completion rate. This suggests that an excessively ambitious target does not necessarily result in better road safety performance and is detrimental to achieving expected fatality reductions., Conclusion: From an empirical perspective, this study revealed a potential interaction effect between quantitative road safety targets and practical fatality reduction performance, providing government officials and policymakers with essential references for future practices on target setting and governance planning in regard to public health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cui, Guo, Li, Zhang, Wang, Yang, Hu, Wong, Bai, Ma and Chen.)

Study Design: Retrospective Exact Matched case-control study., Objectives: Surgical treatment delay in AIS due to family preferences is common. This study aims to quantify the increase in risks as the Cobb angle increases and provide a Quantifiable Risk Reference Table that can be utilized for counseling., Methodology: AIS patients were divided into 3 groups: Group A: Cobb angle 50-60°, Group 61-70°, and Group C Final ≥80°. Each patient in Group C Final who had curve progression were then traced-back-in-time (TBIT) to review the clinical data at earlier presentations at 50-60° (C 1 ), and 61-70° (C 2 ). Patient demographics, radiological, operative, and outcomes data were compared between Group A vs C 1 and Group B vs Group C 2 ., Results: A total of 614 AIS surgeries were reviewed. Utilizing the EM technique, a total of 302 AIS patients were recruited. There were 147, 111, 31, and 32 patients matched in Groups A, B, C 1, and C 2 , respectively. C 2 Final patients had 34% curve pattern change, 23.2% higher incidence of requiring two surgeries, and 17.3% increase in complications. There was a statistically significant increase of 2.4 spinal levels fused, 12% increase in implant density, 35% increase in operative time, 97% increase in intra-operative blood loss, 10% loss of scoliosis correction, 40% longer hospitalization stay, and 36% increase in costs for patients who had curve progression., Conclusion: This study is the first to use a homogenously matched AIS cohort to provide a Quantifiable Risk Reference Table. The Risk Table provides essential knowledge for treating physicians when counseling AIS patients.

Studies suggest that an attentional bias to thin bodies is common among those with high levels of body dissatisfaction, which is a risk factor for, and symptom of, various eating disorders. However, these studies have predominantly been conducted in Western countries with body stimuli involving images of White people. In a preregistered study, we recruited 150 Malaysian Chinese women and 150 White Australian women for a study using standardized images of East Asian and White Australian bodies. To measure attentional bias to thin bodies, participants completed a dot probe task which presented images of women who self-identified their ethnicity as East Asian or as White Australian. Contrary to previous findings, we found no evidence for an association between body dissatisfaction and attentional bias to thin bodies. This lack of association was not affected by participant ethnicity (Malaysian Chinese versus White Australian) or ethnic congruency between participants and body stimuli (own-ethnicity versus other-ethnicity). However, the internal consistency of the dot probe task was poor. These results suggest that either the relationship between body dissatisfaction and attentional bias to thin bodies is not robust, or the dot probe task may not be a reliable measure of attentional bias to body size., Competing Interests: We have no competing interests., (© 2023 The Authors.)

Objective: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment., Methods: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20-79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL)., Results: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7-S1 sagittal vertical axis (SVA) (p < 0.001), C2-7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001)., Conclusion: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2-7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.

Study Design: Prospective cohort study., Objectives: To show population variance in the Inflection Point (IP) and its role in defining maximum Thoracic Kyphosis (TK) and Lumbar Lordosis (LL)., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Dr Wong has received research grants from AbbVie, Galderma, Kiniksa, and Eisai. He has served on the advisory board for Bristol Myers Squibb. Authors Nymeyer and Nedosekin have no conflicts of interest to declare.

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) have recently been established to define a new disease entity, MOG-antibody-associated disease (MOGAD), which is clinically overlapping with multiple sclerosis. MOG-specific antibodies (Abs) from patients are pathogenic, but the precise effector mechanisms are currently still unknown and no therapy is approved for MOGAD. Here, we determined the contributions of complement and Fc-receptor (FcR)-mediated effects in the pathogenicity of MOG-Abs. Starting from a recombinant anti-MOG (mAb) with human IgG1 Fc, we established MOG-specific mutant mAbs with differential FcR and C1q binding. We then applied selected mutants of this MOG-mAb in two animal models of experimental autoimmune encephalomyelitis. First, we found MOG-mAb-induced demyelination was mediated by both complement and FcRs about equally. Second, we found that MOG-Abs enhanced activation of cognate MOG-specific T cells in the central nervous system (CNS), which was dependent on FcR-, but not C1q-binding. The identification of complement-dependent and -independent pathomechanisms of MOG-Abs has implications for therapeutic strategies in MOGAD.

Background and Objectives: Antibodies to CD20 efficiently reduce new relapses in multiple sclerosis (MS), and ocrelizumab has been shown to be effective also in primary progressive MS. Although anti-CD20 treatments efficiently deplete B cells in blood, some B cells and CD20 - plasma cells persist in lymphatic organs and the inflamed CNS; their survival is regulated by the B cell-activating factor (BAFF)/A proliferation-inducing ligand (APRIL) system. The administration of a soluble receptor for BAFF and APRIL, atacicept, unexpectedly worsened MS. Here, we explored the long-term effects of ocrelizumab on immune cell subsets as well as on cytokines and endogenous soluble receptors comprising the BAFF-APRIL system., Methods: We analyzed immune cell subsets and B cell-regulating factors longitudinally for up to 2.5 years in patients with MS treated with ocrelizumab. In a second cohort, we determined B-cell regulatory factors in the CSF before and after ocrelizumab. We quantified the cytokines BAFF and APRIL along with their endogenous soluble receptors soluble B-cell maturation antigen (sBCMA) and soluble transmembrane activator and calcium-modulator and cyclophilin ligand (CAML) interactor (sTACI) using enzyme-linked immunosorbent assays (ELISAs). In addition, we established an in-house ELISA to measure sTACI-BAFF complexes., Results: Ocrelizumab treatment of people with MS persistently depleted B cells and CD20 + T cells. This treatment enhanced BAFF and reduced the free endogenous soluble receptor and decoy sTACI in both serum and CSF. Levels of sTACI negatively correlated with BAFF levels. Reduction of sTACI was associated with formation of sTACI-BAFF complexes., Discussion: We describe a novel effect of anti-CD20 therapy on the BAFF-APRIL system, namely reduction of sTACI. Because sTACI is a decoy for APRIL, its reduction may enhance local APRIL activity, thereby promoting regulatory IgA + plasma cells and astrocytic interleukin (IL)-10 production. Thus, reducing sTACI might contribute to the beneficial effect of anti-CD20 as exogenous sTACI (atacicept) worsened MS., Classification of Evidence: This study provides Class IV evidence that endogenous sTACI in blood and CSF is decreased after ocrelizumab treatment., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

This study aimed to identify radiomic features of primary tumor and develop a model for indicating extrahepatic metastasis of hepatocellular carcinoma (HCC). Contrast-enhanced computed tomographic (CT) images of 177 HCC cases, including 26 metastatic (MET) and 151 non-metastatic (non-MET), were retrospectively collected and analyzed. For each case, 851 radiomic features, which quantify shape, intensity, texture, and heterogeneity within the segmented volume of the largest HCC tumor in arterial phase, were extracted using Pyradiomics. The dataset was randomly split into training and test sets. Synthetic Minority Oversampling Technique (SMOTE) was performed to augment the training set to 145 MET and 145 non-MET cases. The test set consists of six MET and six non-MET cases. The external validation set is comprised of 20 MET and 25 non-MET cases collected from an independent clinical unit. Logistic regression and support vector machine (SVM) models were identified based on the features selected using the stepwise forward method while the deep convolution neural network, visual geometry group 16 (VGG16), was trained using CT images directly. Grey-level size zone matrix (GLSZM) features constitute four of eight selected predictors of metastasis due to their perceptiveness to the tumor heterogeneity. The radiomic logistic regression model yielded an area under receiver operating characteristic curve (AUROC) of 0.944 on the test set and an AUROC of 0.744 on the external validation set. Logistic regression revealed no significant difference with SVM in the performance and outperformed VGG16 significantly. As extrahepatic metastasis workups, such as chest CT and bone scintigraphy, are standard but exhaustive, radiomic model facilitates a cost-effective method for stratifying HCC patients into eligibility groups of these workups.

Objective: The role of the craniocervical complex in spinal sagittal alignment has rarely been analyzed but it may play a fundamental role in postoperative mechanical complications. The aim of the study is to analyze the normative value of the cervical inclination angle (CIA) in an adult asymptomatic multiethnic population., Methods: Standing full-spine EOS of adult asymptomatic volunteers from 5 different countries were analyzed. The CIA was analyzed globally and then in each decade of life. Different ethnicities were compared. Comparisons between different groups was performed using a t-test and statistical significance was considered with a p-value < 0.05., Results: EOS of 468 volunteers were analyzed. The global mean CIA was 80.2° with a maximum difference of 9° between T1 and T12 (p < 0.001). The CIA remains constant until 60 years old then decreases significantly passing from a mean value before 20 years old of 82.25° to 73.65° after 70 years old. A statistically significant difference was found between the Arabics and other ethnicities with the formers having an inferior CIA: this was related to a mean older age (p < 0.05) and higher body mass index (p < 0.05) in the Arabics., Conclusion: The CIA remains constant until 60 years old and then reduces slightly but never under 70°. This angle is helpful to evaluate the lever arm at the upper instrumented vertebra after an adult spinal deformity surgery and could predict the occurrence of a proximal junctional kyphosis when its value is lower than normal. Further clinical studies must confirm this theory.

Study Design: A retrospective cohort study of patients with surgically treated thoracolumbar fractures., Purpose: This study aimed to describe the incidence of adverse events (AEs) after surgical stabilization of thoracolumbar spine injuries and to identify predictive factors for the occurrence of AEs., Overview of Literature: Thoracolumbar spine fractures are frequently present in patients with blunt trauma and are associated with significant morbidity. AEs can occur due to the initial spinal injury or secondary to surgical treatment. There is a lack of emphasis in the literature on the AEs that can occur after operative management of thoracolumbar fractures., Methods: We performed a retrospective review of 199 patients with surgically treated thoracolumbar fractures operated between January 2007 and January 2018. The potential risk factors for the development of AEs as well as the development of common complications were evaluated by univariate analysis, and a multivariate logistic regression analysis was performed to identify independent risk factors predictive of the above., Results: The overall rate of AEs was 46.7%; 83 patients (41.7%) had nonsurgical AEs, whereas 24 (12.1%) had surgical adverse events. The most common AEs were urinary tract infections in 43 patients (21.6%), and hospital-acquired pneumonia in 21 patients (10.6%). On multivariate logistic regression, a Thoracolumbar Injury Classification and Severity (TLICS) score of 8-10 (odds ratio [OR], 6.39; 95% confidence interval [CI], 2.33-17.51), the presence of polytrauma (OR, 2.64; 95% CI, 1.17-5.99), and undergoing open surgery (OR, 2.31; 95% CI, 1.09-4.88) were significant risk factors for AEs. The absence of neurological deficit was associated with a lower rate of AEs (OR, 0.47; 95% CI, 0.31-0.70)., Conclusions: This study suggests the presence of polytrauma, preoperative American Spinal Injury Association score, and TLICS score are predictive of AEs in patients with surgically treated thoracolumbar fractures. The results might also suggest a role for minimally invasive surgical methods in reducing AEs in these patients.

Although putting on a mask over our nose and mouth is a simple but powerful way to protect ourselves and others during a pandemic, face masks may interfere with how we perceive and recognize one another, and hence, may have far-reaching impacts on communication and social interactions. To date, it remains relatively unknown the extent to which wearing a face mask that conceals the bottom part of the face affects the extraction of different facial information. To address this question, we compared young adults' performance between masked and unmasked faces in four different tasks: (1) emotion recognition task, (2) famous face recognition and naming test, (3) age estimation task, and (4) gender classification task. Results revealed that the presence of face mask has a negative impact on famous face recognition and emotion recognition, but to a smaller extent on age estimation and gender classification tasks. More interestingly, we observed a female advantage in the famous face recognition and emotion recognition tasks and a female own-gender bias in gender categorisation and age estimation tasks. Overall, these findings allude to the lack of malleability of the adulthood face recognition and perceptual systems., (© 2022. The Author(s).)

Accurate demographic data are critical for comprehending and treating cutaneous T-cell lymphoma (CTCL). Our research aimed to determine the demographics and incidence trends of CTCL patients in Arkansas compared to those of the national CTCL population to recognize the underlying disparities. We collected data from 143 CTCL patients at the University of Arkansas for Medical Sciences (UAMS) and national CTCL patient data from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis revealed that males are affected more than females across all ages and races. CTCL incidence and mortality data show that CTCL has a steady increase at the national level and in Arkansas while disproportionately affecting the young black male population. In Arkansas, more than one-third of black patients presented at an advanced stage (IIB+) compared to one-fifth in the white population, and the mean age of death was more than a decade younger for black (60 years) than for white patients (74.6 years). Nationally, black male patients had the greatest mortality rate (0.5) compared to 0.32 for white males. CTCL is 2.23 and 2.38 times more prevalent in urban versus rural areas in Arkansas and nationally, respectively. Most Arkansas patients reside near major interstates and chemical-emitting sites. In conclusion, our demographic analysis of Arkansas and national CTCL patients verifies recent trends toward more aggressive presentations in young black male patients, and our geographic findings suggest possible environmental risk factors.

Depression is one of the most prevalent mental disorders associated with reductions in bone mineral density and increased fracture risk. Fluoxetine is a highly prescribed selective serotonin reuptake inhibitor (SSRI) in the treatment of depression and is reported to be a risk factor for fractures. The present study examined the effect of fluoxetine on bone microarchitecture and the mechanical properties under chronic mild stress (CMS), a rodent model of depression. Thirty-one 6-9 week-old rats were allocated to 4 groups: 1) CMS + fluoxetine group (n = 10), 2) fluoxetine-only group (n = 5), 3) CMS + placebo group (n = 10) and 4) control group (no CMS and treatment) (n = 6). After 16 weeks, bone microarchitecture of the distal femur was analyzed by µCT. Mechanical properties were assessed by the three-point bending test, and antidepressant efficacy was determined by sucrose preference and forced swimming tests. Significant correlations were found between volume of sucrose intake and bone volume/tissue volume (BV/TV) (p = 0.019) and elastic absorption energy (p = 0.001) in the fluoxetine only group. The fluoxetine-only group showed significantly higher in the second moment of area in y-direction (p = 0.0298), horizontal outer diameter (mm) (p = 0.0488) and average midshaft thickness (mm) (p = 0.00047) than control group. Comparing with the control group, there was a significant reduction in trabecular number (Tb.N) in the CMS + fluoxetine group (p = 0.026) but not the fluoxetine-only group (p > 0.05). Significant increases in trabecular separation were observed in the metaphysis of CMS + placebo (p = 0.003) and CMS + fluoxetine (p = 0.004) groups when compared to the control group but not in the fluoxetine-only group (p > 0.05). During the three-point bending test, the fluoxetine-only group demonstrated significantly higher structural strength than controls (p = 0.04). Micro computed tomography (µCT) slices showed loss of trabecular bone in the metaphysis region of the CMS + fluoxetine and CMS + placebo groups but not the fluoxetine-only and control groups. In an animal model of depression, the adverse effect on the bone microarchitecture was caused by CMS but not by fluoxetine. Without exposure to CMS, fluoxetine significantly increased the cross-sectional area, trabecular bone area, structural strength and osteoblasts / bone area as compared to control condition., (© 2022. The Author(s).)

Although the positive effects of congruency between stimuli are well replicated in face memory paradigms, mixed findings have been found in face matching. Due to the current COVID-19 pandemic, face masks are now very common during daily life outdoor activities. Thus, the present study aims to further explore congruency effects in matching faces partially occluded by surgical masks. Observers performed a face matching task consisting of pairs of faces presented in full view (i.e., full-view condition), pairs of faces in which only one of the faces had a mask (i.e., one-mask condition), and pairs of faces in which both faces had a mask (i.e., two-mask condition). Although face masks disrupted performance in identity match and identity mismatch trials, in match trials, we found better performance in the two-mask condition compared to the one-mask condition. This finding highlights the importance of congruency between stimuli on face matching when telling faces together., (© 2022. The Author(s).)

Aim: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome., Methods: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms., Results: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo., Conclusion: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome., (© 2021 The Authors. Psychiatry and Clinical Neurosciences © 2021 Japanese Society of Psychiatry and Neurology.)

Study Design: Retrospective cohort study., Purpose: To evaluate the incidence and presentation of symptomatic failures (SFs) after metastatic spine tumor surgery (MSTS). To identify the associated risk factors. To categorize SFs based on the management in these patients., Overview of Literature: Few studies have reported on the incidence (1.9%-16%) and risk factors of SF after MSTS. It is unclear whether all SFs, occurring in MSTS-patients, result in revision surgery., Methods: We conducted a retrospective analysis on 288 patients (246 for final analysis) who underwent MSTS between 2005-2015. Data collected were demographics and peri/postoperative clinical and radiological features. Early and late radiological SF were defined as presentation before and after 3 months from index surgery, respectively. Univariate and multivariate models of competing risk regression analysis were designed to determine the risk factors for SF with death as a competing event., Results: We observed 14 SFs (5.7%) in 246 patients; 10 (4.1%) underwent revision surgery. Median survival was 13.4 months. The mean age was 58.8 years (range, 21-87 years); 48.4% were women. The median time to failure was 5 months (range, 1-60 months). Patients with SF were categorized into three groups: (1) SF when the primary implant was revised (n=5, 35.7%); (2) peri-construct progression of disease requiring extension (n=5, 35.7%); and (3) SFs that did not warrant revision (n=4, 28.5%). Four patients (28.5%) presented with early failure. SF commonly occurred at the implant-bone interface (9/14) and all patients had a spinal instability neoplastic score (SINS) >7. Thirteen patients (92.8%) who developed failure had fixation spanning junctional regions. Multivariate competing risk regression showed that preoperative Eastern Cooperative Oncology Group score was a significant risk factor for implant failure (adjusted sub-hazard ratio, 7.0; 95% confidence interval, 1.63-30.07; p<0.0009)., Conclusions: The incidence of SF (5.7%) was low in patients undergoing MSTS although these patients did not undergo spinal fusion. Preoperative ambulators involved a 7 times higher risk of failure than non-ambulators. Preoperative SINS >7 and fixations spanning junctional regions were associated with SF. Majority of construct failures occurred at the implant-bone interface.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare non-Hodgkin's lymphoma that arises as a single, or multiple dome-shaped tumours on the skin. The histology is characterised by the presence of atypical lymphocytes with large irregularly shaped nuclei that express the surface marker CD30. There can be significant heterogeneity in clinical manifestation and histological pattern and in rare cases accurate diagnosis can be a challenge. Here, we present an unusual case presentation of cutaneous CD30+ anaplastic large cell lymphoma with significant granulomatous histology pattern that mimicked sarcoid. After a lack of durable response to treatments that included glucocorticoid and methotrexate, targeted treatment with anti-CD30 monoclonal antibody drug conjugate (brentuximab vedotin) yielded long-term clinical remission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma (CTCL) that transforms from mature, skin-homing T cells and progresses during the early stages in the skin. The role of the skin microenvironment in MF development is unclear, but recent findings in a variety of cancers have highlighted the role of stromal fibroblasts in promoting or inhibiting tumorigenesis. Stromal fibroblasts are an important part of the cutaneous tumor microenvironment (TME) in MF. Here we describe studies into the interaction of TME-fibroblasts and malignant T cells to gain insight into their role in CTCL., Methods: Skin from normal (n = 3) and MF patients (n = 3) were analyzed for FAPα by immunohistochemistry. MyLa is a CTCL cell line that retains expression of biomarkers TWIST1 and TOX that are frequently detected in CTCL patients. MyLa cells were cultured in the presence or absence of normal or MF skin derived fibroblasts for 5 days, trypsinized to detached MyL a cells, and gene expression analyzed by RT-PCR for MF biomarkers (TWIST1 and TOX), Th1 markers (IFNG, TBX21), Th2 markers (GATA3, IL16), and proliferation marker (MKI67). Purified fibroblasts were assayed for VIM and ACTA2 gene expression. Cellular senescence assay was performed to assess senescence., Results: MF skin fibroblast showed increased expression of FAP-α with increasing stage compared to normal. Normal fibroblasts co-cultured with MyLa cells suppressed expression of TWIST1 (p < 0.0006), and TOX (p < 0.03), GATA3 (p < 0.02) and IL16 (p < 0.03), and increased expression of IFNG (p < 0.03) and TBX21 (p < 0.03) in MyLa cells. In contrast, MyLa cells cultured with MF fibroblasts retained high expression of TWIST1, TOX and GATA3. MF fibroblasts co-culture with MyLa cells increased expression of IL16 (p < 0.01) and IL4 (p < 0.02), and suppressed IFNG and TBX21 in MyLa cells. Furthermore, expression of MKI67 in MyLa cells was suppressed by normal fibroblasts compared to MF fibroblasts., Conclusion: Skin fibroblasts represent important components of the TME in MF. In co-culture model, normal and MF fibroblasts have differential influence on T-cell phenotype in modulating expression of Th1 cytokine and CTCL biomarker genes to reveal distinct roles with implications in MF progression.

It is widely accepted that holistic processing is important for face perception. However, it remains unclear whether the other-race effect (ORE) (i.e. superior recognition for own-race faces) arises from reduced holistic processing of other-race faces. To address this issue, we adopted a cross-cultural design where Malaysian Chinese, African, European Caucasian and Australian Caucasian participants performed four different tasks: (1) yes-no face recognition, (2) composite, (3) whole-part and (4) global-local tasks. Each face task was completed with unfamiliar own- and other-race faces. Results showed a pronounced ORE in the face recognition task. Both composite-face and whole-part effects were found; however, these holistic effects did not appear to be stronger for other-race faces than for own-race faces. In the global-local task, Malaysian Chinese and African participants demonstrated a stronger global processing bias compared to both European- and Australian-Caucasian participants. Importantly, we found little or no cross-task correlation between any of the holistic processing measures and face recognition ability. Overall, our findings cast doubt on the prevailing account that the ORE in face recognition is due to reduced holistic processing in other-race faces. Further studies should adopt an interactionist approach taking into account cultural, motivational, and socio-cognitive factors.

Study Design: An original article describing a comprehensive methodology for making a traditional spine surgery clinic telemedicineready in terms of logistical considerations and workflow., Purpose: The aim of this study is to promote the use of telemedicine via videoconferencing to reduce human exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and reduce the risk of coronavirus disease 2019 (COVID-19) transmission at outpatient clinics., Overview of Literature: The COVID-19 pandemic is the biggest healthcare crisis in the 21st century. Until a vaccine is developed or herd immunity against SARS-CoV-2 is achieved, social distancing to avoid crowding is an important strategy to reduce disease transmission and resurgence. Telemedicine has already been applied in the field of orthopedics with encouraging results., Methods: We reviewed the evidence behind telemedicine and described our clinical protocol, patient selection criteria, and workflow for telemedicine. We discussed a simple methodology to convert pre-existing traditional clinic resources into telemedicine tools, along with future challenges., Results: Our methodology was successfully and easily applied in our clinical practice, with a streamlined workflow allowing our spine surgery service to implement telemedicine as a consultation modality in line with the national recommendations of social distancing., Conclusions: Telemedicine was well incorporated into our outpatient practice using the above workflow. We believe that the use of telemedicine via videoconferencing can become part of the new normal and a safe strategy for healthcare systems as both a medical and an economic countermeasure against COVID-19.

Study Design: Prospective radiographic comparative study., Purpose: To compare and understand the load-bearing properties of each functional spinal unit (FSU) using three commonly assumed, physiological, spinal postures, namely, the flexed (slump sitting), erect (standing) and extended (backward bending) postures., Overview of Literature: Sagittal spinal alignment is posture-dependent and influences the load-bearing properties of the spine. The routine placement of intervertebral cages "as anterior as possible" to correct deformity may compromise the load-bearing capabilities of the spine, leading to complications., Methods: We recruited young patients with nonspecific low back pain for <3 months, who were otherwise healthy. Each patient had EOS images taken in the flexed, erect and extended positions, in random order, as well as magnetic resonance imaging to assess for disk degeneration. Angular and disk height measurements were performed and compared in all three postures using paired t-tests. Changes in disk height relative to the erect posture were caclulated to determine the alignment-specific load-bearing area of each FSU., Results: Eighty-three patients (415 lumbar intervertebral disks) were studied. Significant alignment changes were found between all three postures at L1/2, and only between erect and flexion at the other FSUs. Disk height measurements showed that the neutral axis of the spine, marked by zones where disk heights did not change, varied between postures and was level specific. The load-bearing areas were also found to be more anterior in flexion and more posterior in extension, with the erect spine resembling the extended spine to a greater extent., Conclusions: Load-bearing areas of the lumbar spine are sagittal alignment-specific and level-specific. This may imply that, depending on the surgical realignment strategy, attention should be paid not just to placing an intervertebral cage "as anterior as possible" for generating lordosis, but also on optimizing load-bearing in the lumbar spine.