Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.

Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca2+ release and mitogen-activated protein kinase (MAPK) pathway activation. The high specificity of the designed agonists reveals distinct roles for two FGFR splice variants in driving arterial endothelium and perivascular cell fates during early vascular development. Our designed modular assemblies should be broadly useful for unraveling the complexities of signaling in key developmental transitions and for developing future therapeutic applications.

Heparin is essential for optimal cell signaling by FGF21 and for regulation of ßKlotho cellular stability.

While important insights were gained about how FGF21 and other endocrine fibroblast growth factors (FGFs) bind to Klotho proteins, the exact mechanism of Klotho/FGF receptor assembly that drives receptor dimerization and activation has not been elucidated. The prevailing dogma is that Klotho proteins substitute for the loss of heparan sulfate proteoglycan (HSPG) binding to endocrine FGFs by high-affinity binding of endocrine FGF molecules to Klotho receptors. To explore a potential role of HSPG in FGF21 signaling, we have analyzed the dynamic properties of FGF21-induced FGF21-ßKlotho-FGFR1c complexes on the surface of living wild-type (WT) or HSPG-deficient Chinese hamster ovary (CHO) cells by employing quantitative single-molecule fluorescence imaging analyses. Moreover, detailed analyses of FGF21 and FGF1 stimulation of cellular signaling pathways activated in WT or in HSPG-deficient CHO cells are also analyzed and compared. These experiments demonstrate that heparin is required for the formation of FGF21-ßKlotho-FGFR1c complexes on the cell membrane and that binding of heparin or HSPG to FGFR1c is essential for optimal FGF21 stimulation of FGFR1c activation, mitogen-activated protein kinase responses, and intracellular Ca2+ release. It is also shown that FGF1 binding stimulates assembly of ßKlotho and FGFR1c on cell membranes, resulting in endocytosis and degradation of ßKlotho. We conclude that heparin or HSPG is essential for FGF21 signaling and for regulation of ßKlotho cellular stability by acting as a coligand of FGFR1c.

Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis.

The phosphoinositide-3 kinase (PI-3K)/AKT cell survival pathway is an important pathway activated by EGFR signaling. Here we show, that in addition to previously described critical components of this pathway, i.e., the docking protein Gab1, the PI-3K/AKT pathway in epithelial cells is regulated by the exocyst complex, which is a vesicle tether that is essential for exocytosis. Using live-cell imaging, we demonstrate that PI(3,4,5)P3 levels fluctuate at the membrane on a minutes time scale and that these fluctuations are associated with local PI(3,4,5)P3 increases at sites where recycling vesicles undergo exocytic fusion. Supporting a role for exocytosis in PI(3,4,5)P3 generation, acute promotion of exocytosis by optogenetically driving exocyst-mediated vesicle tethering up-regulates PI(3,4,5)P3 production and AKT activation. Conversely, acute inhibition of exocytosis using Endosidin2, a small-molecule inhibitor of the exocyst subunit Exo70 (also designated EXOC7), or inhibition of exocyst function by siRNA-mediated knockdown of the exocyst subunit Sec15 (EXOC6), impairs PI(3,4,5)P3 production and AKT activation induced by EGF stimulation of epithelial cells. Moreover, prolonged inhibition of EGF signaling by EGFR tyrosine kinase inhibitors results in spontaneous reactivation of AKT without a concomitant relief of EGFR inhibition. However, this reactivation can be negated by acutely inhibiting the exocyst. These experiments demonstrate that exocyst-mediated exocytosis-by regulating PI(3,4,5)P3 levels at the plasma membrane-subserves activation of the PI-3K/AKT pathway by EGFR in epithelial cells.

Genome-wide screening reveals the genetic basis of mammalian embryonic eye development.

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. RESULTS: Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. CONCLUSIONS: Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

Deep-Learning Automation of Preoperative Radiographic Parameters Associated With Early Periprosthetic Femur Fracture After Total Hip Arthroplasty.

BACKGROUND: The radiographic assessment of bone morphology impacts implant selection and fixation type in total hip arthroplasty (THA) and is important to minimize the risk of periprosthetic femur fracture (PFF). We utilized a deep-learning algorithm to automate femoral radiographic parameters and determined which automated parameters were associated with early PFF. METHODS: Radiographs from a publicly available database and from patients undergoing primary cementless THA at a high-volume institution (2016 to 2020) were obtained. A U-Net algorithm was trained to segment femoral landmarks for bone morphology parameter automation. Automated parameters were compared against that of a fellowship-trained surgeon and compared in an independent cohort of 100 patients who underwent THA (50 with early PFF and 50 controls matched by femoral component, age, sex, body mass index, and surgical approach). RESULTS: On the independent cohort, the algorithm generated 1,710 unique measurements for 95 images (5% lesser trochanter identification failure) in 22 minutes. Medullary canal width, femoral cortex width, canal flare index, morphological cortical index, canal bone ratio, and canal calcar ratio had good-to-excellent correlation with surgeon measurements (Pearson's correlation coefficient: 0.76 to 0.96). Canal calcar ratios (0.43 ± 0.08 versus 0.40 ± 0.07) and canal bone ratios (0.39 ± 0.06 versus 0.36 ± 0.06) were higher (P < .05) in the PFF cohort when comparing the automated parameters. CONCLUSIONS: Deep-learning automated parameters demonstrated differences in patients who had and did not have early PFF after cementless primary THA. This algorithm has the potential to complement and improve patient-specific PFF risk-prediction tools.

Periodontitis is associated with the development of fungal sinusitis: A nationwide 12-year follow-up study.

AIM: The incidence of fungal sinusitis is increasing; however, its pathophysiology has not been investigated previously. We investigate the effect of periodontitis on the incidence of fungal sinusitis over a 12-year follow-up period using nationwide population-based data. MATERIALS AND METHODS: The periodontitis group was randomly selected from the National Health Insurance Service database. The non-periodontitis group was obtained by propensity score matching considering several variables. The primary end point was the diagnosis of sinonasal fungal balls (SFBs) and invasive fungal sinusitis (IFS). RESULTS: The periodontitis and non-periodontitis groups included 12,442 and 12,442 individuals, respectively. The overall adjusted hazard ratio (aHR) for SFBs in the periodontitis group was 1.46 (p = .002). In subgroup analysis, the aHR for SFBs was 1.59 (p = 0.008) for those with underlying chronic kidney disease (CKD), 1.58 (p = .022) for those with underlying atopic dermatitis, 1.48 (p = .019) for those with chronic obstructive pulmonary disease (COPD), and 1.36 (p = .030) for those with diabetes mellitus (DM), but these values are applicable only when considering the relationship between periodontitis and SFB. The aHR for IFS in the periodontitis group was higher than in the non-periodontitis group (2.80; p = .004). CONCLUSIONS: The risk of SFBs and IFS increased after diagnosis of periodontitis. This trend is often more severe in patients with DM, COPD, or CKD, but this association with underlying diseases is applicable only when considering the association between periodontitis and fungal sinusitis.

FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho.

The three members of the endocrine-fibroblast growth factor (FGF) family, FGF19, 21, and 23 are circulating hormones that regulate critical metabolic processes. FGF23 stimulates the assembly of a signaling complex composed of α-Klotho (KLA) and FGF receptor (FGFR) resulting in kinase activation, regulation of phosphate homeostasis, and vitamin D levels. Here we report that the C-terminal tail of FGF23, a region responsible for KLA binding, contains two tandem repeats, repeat 1 (R1) and repeat 2 (R2) that function as two distinct ligands for KLA. FGF23 variants with a single KLA binding site, FGF23-R1, FGF23-R2, or FGF23-wild type (WT) with both R1 and R2, bind to KLA with similar binding affinity and stimulate FGFR1 activation and MAPK response. R2 is flanked by two cysteines that form a disulfide bridge in FGF23-WT; disulfide bridge formation in FGF23-WT is dispensable for KLA binding and for cell signaling via FGFRs. We show that FGF23-WT stimulates dimerization and activation of a chimeric receptor molecule composed of the extracellular domain of KLA fused to the cytoplasmic domain of FGFR and employ total internal reflection fluorescence microscopy to visualize individual KLA molecules on the cell surface. These experiments demonstrate that FGF23-WT can act as a bivalent ligand of KLA in the cell membrane. Finally, an engineered Fc-R2 protein acts as an FGF23 antagonist offering new pharmacological intervention for treating diseases caused by excessive FGF23 abundance or activity.

A practical guide to the development and deployment of deep learning models for the orthopedic surgeon: part II.

Deep learning has the potential to be one of the most transformative technologies to impact orthopedic surgery. Substantial innovation in this area has occurred over the past 5 years, but clinically meaningful advancements remain limited by a disconnect between clinical and technical experts. That is, it is likely that few orthopedic surgeons possess both the clinical knowledge necessary to identify orthopedic problems, and the technical knowledge needed to implement deep learning-based solutions. To maximize the utilization of rapidly advancing technologies derived from deep learning models, orthopedic surgeons should understand the steps needed to design, organize, implement, and evaluate a deep learning project and its workflow. Equipping surgeons with this knowledge is the objective of this three-part editorial review. Part I described the processes involved in defining the problem, team building, data acquisition, curation, labeling, and establishing the ground truth. Building on that, this review (Part II) provides guidance on pre-processing and augmenting the data, making use of open-source libraries/toolkits, and selecting the required hardware to implement the pipeline. Special considerations regarding model training and evaluation unique to deep learning models relative to "shallow" machine learning models are also reviewed. Finally, guidance pertaining to the clinical deployment of deep learning models in the real world is provided. As in Part I, the focus is on applications of deep learning for computer vision and imaging.

Geographic Variation in Knee Phenotypes Based on the Coronal Plane Alignment of the Knee Classification: A Systematic Review.

BACKGROUND: The extent of geographic variation in knee phenotypes remains unclear. The Coronal Plane Alignment of the Knee (CPAK) Classification proposes 9 coronal plane phenotypes based on constitutional limb alignment and joint line obliquity. This systematic review aims to examine differences in the distributions of CPAK types across geographic regions. METHODS: A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting distributions of knee phenotypes according to the CPAK classification for healthy and/or arthritic knees were included. RESULTS: There were 7 studies included, accounting for 5,964 knees in 3,917 subjects. Among healthy knees (n = 1,214), CPAK type II was the most common type in Belgium (39.2%), Taiwan (39.3%), and India (25.6%). Among arthritic knees (n = 2,804), CPAK type I was the most common in France (33.4%), India (58.8%), and Japan (53.8%), whereas CPAK type II was the most common in Australia (32.8%). The proportion of CPAK type I and II knees varied significantly across geographic regions among healthy (P < .01) and arthritic knees (P < .01). CONCLUSION: Significant variation in CPAK distributions exists between countries. Further work is needed to delineate racial and sexual differences in CPAK types, which were not explored in this article. A better understanding of population-level variability in knee phenotypes may enable orthopaedic surgeons to offer a more personalized approach to knee arthroplasty.

Complication Rate After Primary Total Hip Arthroplasty Using the Posterior Approach and Enabling Technology: A Consecutive Series of 2,888 Hips.

BACKGROUND: Total hip arthroplasty (THA) is a safe and effective procedure; however, complications such as dislocation, fracture, and infection still occur. It is still unclear whether the dislocation rate via the posterior approach (PA) is better, equal, or worse than the direct anterior approach. Our aim was to report the primary THA dislocation rate via the PA using enabling technology in a large consecutive series of patients. METHODS: A retrospective cohort of 2,888 primary THAs were reviewed at a single, high-volume, academic institution from January 2018 to September 2021. All patients underwent a THA by 4 fellowship-trained orthopaedic surgeons through the PA with enabling technology. Overall dislocation and readmission rates within 90 days and up to 3 years were analyzed. RESULTS: Of the 2,888 procedures, a total of 39 patients had complications related to the surgery during the 3-year follow-up period. There were 10 patients (0.35%) who experienced a dislocation, with half undergoing surgical revision. Of the 39 patients who experienced complications, 37 (1.3%) were readmitted and 2 underwent revision during their hospital stay. Postoperative periprosthetic fractures were the most common cause for readmission and reoperation at a rate of 0.52% and 0.52%, respectively. CONCLUSION: The dislocation rate of 0.35% is one of the lowest reported rates via the PA at a mean follow up of 2.1 years and is comparable to previously published rates using alternate approaches. Using contemporary THA with enabling technology, the PA is a reliable approach with respect to dislocation and complication rates after primary THA.

Standardized Fixation Zones and Cone Assessments for Revision Total Knee Arthroplasty Using Deep Learning.

BACKGROUND: Achieving adequate implant fixation is critical to optimize survivorship and postoperative outcomes after revision total knee arthroplasty (rTKA). Three anatomical zones (ie, epiphysis, metaphysis, and diaphysis) have been proposed to assess fixation, but are not well-defined. The purpose of the study was to develop a deep learning workflow capable of automatically delineating rTKA zones and cone placements in a standardized way on postoperative radiographs. METHODS: A total of 235 patients who underwent rTKA were randomly partitioned (6:2:2 training, validation, and testing split), and a U-Net segmentation workflow was developed to delineate rTKA fixation zones and assess revision cone placement on anteroposterior radiographs. Algorithm performance for zone delineation and cone placement were compared against ground truths from a fellowship-trained arthroplasty surgeon using the dice segmentation coefficient and accuracy metrics. RESULTS: On the testing cohort, the algorithm defined zones in 98% of images (8 seconds/image) using anatomical landmarks. The dice segmentation coefficient between the model and surgeon was 0.89 ± 0.08 (interquartile range [IQR]:0.88-0.94) for femoral zones, 0.91 ± 0.08 (IQR: 0.91-0.95) for tibial zones, and 0.90 ± 0.05 (IQR:0.88-0.94) for all zones. Cone identification and zonal cone placement accuracy were 98% and 96%, respectively, for the femur and 96% and 89%, respectively, for the tibia. CONCLUSION: A deep learning algorithm was developed to automatically delineate revision zones and cone placements on postoperative rTKA radiographs in an objective, standardized manner. The performance of the algorithm was validated against a trained surgeon, suggesting that the algorithm demonstrated excellent predictive capabilities in accordance with relevant anatomical landmarks used by arthroplasty surgeons in practice.

A predictive model based on site-specific risk factors of recurrence regions in endometrial cancer patients.

OBJECTIVE: This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated. METHODS: Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer. RESULTS: The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis. CONCLUSION: We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients.

Polyethylene liner cementation into a well-fixed metal acetabular shell for the management of periacetabular osteolysis: a systematic review.

PURPOSE: Although various papers have reported on the clinical performance of cup retention with cementation of a new liner and bone grafting in the management of well-fixed cups with polyethylene wear and periacetabular osteolysis after total hip arthroplasty (THA), no systematic review of this topic has been published to date. METHODS: Medline, EMBASE and Cochrane Library were searched for articles published from January 1999 to January 2019 using "osteolysis" AND "well-fixed", "osteolysis" AND "retro-acetabular", "bone graft" AND ("retention" OR "retained" OR "stable") AND "cup", and "cemented liner" AND "well-fixed". RESULTS: Nine articles were selected for review (186 cases, 76.1 months mean follow-up). The overall revision rate was 11.3% (21 hips) most commonly due to aseptic loosening (9/186 hips), dislocation (8/186 hips), and liner wear progression (2/186 cases). The reported square size of osteolytic lesions ranged from a mean of 465.84 mm2 to a max of 4,770 mm2. Almost all reported lesions treated with bone grafts resolved or did not progress 97% (72/74). All studies indicated improved pain and functional scores at follow-up. CONCLUSION: Cementation of a new liner with periacetabular bone grafting provides an alternative option to isolated liner exchange and cup revision for the management of periacetabular osteolysis in well-fixed cups with a disrupted locking mechanism or unavailable exchange liner. Further higher quality studies are required in order to examine if the use of highly cross-linked polyethylene, highly porous-coated cups, hydroxyapatite-coated cups, and small-diameter cups influence the clinical outcome of liner cementation in well-fixed cups with periacetabular osteolysis.

Preparation of multilayer periodic nanopatterned WO3-based photoanode by reverse nanoimprinting for water splitting.

Photoelectrochemical (PEC) water splitting has been studied extensively as an environmentally friendly technology for hydrogen production using solar energy. WO3is considered a promising semiconducting material for photoanodes due to its high electron mobility, good hole diffusion length, and chemical stability. Periodic nanostructures of WO3have been investigated for enhancing the PEC performance of WO3-based photoanodes. In this study, facile fabrication of periodic nanostructures of WO3was achieved using reverse nanoimprint lithography, and the multilayer stacking of nanopatterned WO3film was also confirmed. The multilayer nanopatterned WO3films were used as photoanodes for PEC water splitting. The performance of the fabricated photoanode in PEC was 2 times higher than that of planar WO3film due to its higher light absorbance and lower charge transfer resistance.

Cervical spine degenerative disease is an independent risk factor for increased revision rate following total knee arthroplasty.

INTRODUCTION: The relationship between cervical degenerative pathology and total knee arthroplasty (TKA) revision rates is not well understood. The aim of the study was to determine whether cervical spine degenerative diseases have a role in complications following TKA within 2 years. METHODS: Data were collected from the Humana insurance database using the PearlDiver Patient Records Database from 2007-2017. Patients who had a primary TKA were identified using Current Procedural Terminology (CPT) code 27,447, and patients with degenerative cervical disease were identified using CPT and International Classification of Diseases (ICD) codes. Data on patients' demographics, comorbidities and postoperative complications were recorded and analyzed with univariate and multivariate analysis with significance set at p < 0.05. A Kaplan-Meier analysis was conducted to estimate the 1- and 2-year rates of survival free from revision. RESULTS: A total of 81,873 patients were included in this study. Following multivariate analysis, cervical spine degenerative disease patients were at increased risk of all-cause revision surgery following 1 year (OR: 1.342 95% CI: 1.149-1.569; p < 0.001) and 2 year (OR: 1.338; 95% CI: 1.184-1.512; p < 0.001). At 2 years, patients with cervical spine degenerative disease had a survival rate of 97.7%, while the survival rate was 99.2% among the non-cervical degenerative cohort. CONCLUSIONS: Based on these results, patients with cervical spine degenerative pathology should be counseled that their spinal pathology may impair outcomes following TKA.

Direct Visualization of Microscale Dynamics of Water Droplets on under-Oil-Hydrophilic Membranes by Using Synchrotron White-Beam X-ray Microimaging Techniques.

Despite considerable academical and practical interests on separation of water-in-oil emulsion via special wettable membranes, fundamental understanding on microscale dynamics of water droplets on under-oil-hydrophilic membranes (UOHMs) at early stages during separation is still very preliminary due to temporal and spatial resolution of existing visualization techniques. To this end, we here succeed in a direct microscopic visualization of separation processes of water droplets on the UOHMs by employing a high-speed, two-dimensional synchrotron white-beam X-ray microimaging technique. During the separation of water-in-oil emulsion, microscale dynamic behaviors of water droplets on hydrophilic membrane surfaces immersed in the different oil media (i.e., hexane, kerosene, and light and heavy mineral oils) and oil films between water droplets and membrane surfaces are visualized and analyzed.

Effects of Alzheimer's disease and Lewy body disease on subcortical atrophy.

BACKGROUND AND PURPOSE: Subcortical structures are affected by neurodegeneration in Alzheimer's disease (AD) and Lewy body disease (LBD). Although the co-occurrence of AD and LBD pathologies and their possible interaction have been reported, the effect of AD and LBD on subcortical structures remains unknown. The effects of AD and LBD on subcortical atrophy and their relationship with cognitive dysfunction were investigated. METHODS: The cross-sectional study recruited 42 patients with pure AD related cognitive impairment (ADCI), 30 patients with pure LBD related cognitive impairment (LBCI), 58 patients with mixed ADCI and LBCI, and 29 normal subjects. A general linear model was used to compare subcortical volume and shape amongst the groups, to investigate the independent and interaction effects of ADCI and LBCI on subcortical shape and volume, and to analyze the relationship between subcortical volume and cognitive dysfunction in each group. RESULTS: Alzheimer's disease related cognitive impairment and LBCI were independently associated with subcortical atrophies in the hippocampus and amygdala and in the hippocampus and putamen respectively, but their interaction effect was not significant. Compared to the control group, the pure LBCI group exhibited additional local atrophies in the amygdala, caudate and thalamus. Subcortical atrophies correlated differently with cognitive dysfunction according to the underlying causes of cognitive dysfunction. CONCLUSIONS: The patterns of subcortical atrophies and their correlation with cognitive dysfunction differ according to the underlying AD, LBD or concomitant AD and LBD.

Diagnostic performance of interferon-gamma release assay for diagnosis of tuberculous pericarditis: A meta-analysis.

BACKGROUND: The diagnosis of tuberculous pericarditis is difficult to set, not only for its non-specific clinical presentation, but also for the lack of useful diagnostic tests. We comprehensively evaluate the overall diagnostic accuracy of Interferon-gamma release assays (IGRA) upon tuberculous pericarditis by meta-analysis. METHODS: We searched PubMed, Embase and Cochrane Library database from the earliest available date of indexing through April 30, 2019. The study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2) checklist. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-) and constructed summary receiver operating characteristic curves parameters. RESULTS: Across six results from five studies (415 patients), the pooled sensitivity for IGRA methods was 0.94 (95% confidence interval [CI]; 0.87-0.98) with heterogeneity (χ2  = 69.9, P = .01) and a pooled specificity of 0.94 (95% CI; 0.75-0.94) without heterogeneity (χ2  = 41.1, P = .13). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 16.8 (95% CI; 8.0-35.4) and negative likelihood ratio (LR-) of 0.06 (95% CI; 0.03-0.13). The pooled diagnostic odds ratio was 278 (95% CI; 114-6806). CONCLUSIONS: Interferon-gamma release assays demonstrated good sensitivity and specificity for diagnosis of tuberculous pericarditis. At present, the literature regarding remains the use of IGRA for diagnosis of tuberculous pericarditis still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of IGRA test for the diagnosis of tuberculous pericarditis.

Comparative split-face study of durational changes in hyaluronic acid fillers for mid-face volume augmentation.

Subsequent changes after injection should be considered when determining the precise volume of injected dermal filler. Several studies have used scoring systems to evaluate facial volumes; however, these scoring systems are not particularly objective. This present study aimed to evaluate the volumetric changes over time on three-dimensional (3D) images and the maintenance potential of various hyaluronic acid (HA) fillers used for mid-face volume augmentation. This split-face clinical study included nine Korean subjects who each received a mid-facial injection of the test filler (B) on one side and a random control filler (J, R, or Y) on the contralateral side. Global, photographic, and 3D scanning assessments were conducted at baseline and after 30 min, 3 days, and 2, 4, 12, and 24 weeks. In all nine cases, the 3D images revealed the largest differences in height where the test filler (B) was injected. The results of subjective scoring systems correlated with the results of 3D imaging. The volumes of monophasic fillers (B and J) were maintained for longer periods of time than those of biphasic fillers (R and Y). The B filler yielded excellent volumizing and spreading effects and good injectability. This filler would be suitable for injection into high-pressure areas, such as the lateral cheek, chin, and nasolabial fold. Moreover, the 3D imaging analysis provided objective and digitized data. The present authors hope that their data will allow physicians to better understand the durational changes in HA fillers and, thus, provide accurate predictions to their patients.

Comparing the Montreal Cognitive Assessment and Rowland Universal Dementia Assessment Scale in a multicultural rehabilitation setting.

In Australia it is recommended that all older people undergoing rehabilitation have a cognitive screen. We performed a longitudinal study comparing the correlation of two cognitive screening tools - the Rowland Universal Dementia Assessment Scale (RUDAS) and Montreal Cognitive Assessment (MoCA) with discharge outcomes in a geriatric inpatient setting. The RUDAS cut-off (<23/30) was associated with discharge to a nursing home (sensitivity 52%, specificity 70%). This was also noted with a MoCA cut-off <18/30 (sensitivity 57%, specificity 69%). Furthermore the association between the RUDAS and discharge destination was independent of its association with the Functional Independence Measure (r = 0.116; P = 0.275) and had a shorter administration time. Both RUDAS and MoCA scores could be used as predictors of discharge destination in a multicultural population.