Search

Abstract Background In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS‐based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS‐based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images. Methods A total of 529 patients who received PS‐based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet‐b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1‐score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models. Results The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412). Conclusion The DL models demonstrated stable performance in identifying the brand of PS‐based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.

Abstract Objective Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic‐related migration disorder. It has been attributed to loss‐of‐function of the ADGRG1 gene, which encodes an adhesion G protein‐coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro). Methods We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole‐exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting. Results The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole‐exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High‐amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre‐school age. Partial callosotomy provided short‐term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3. Significance Sleep EEG findings of high‐amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression.

Abstract Retrospective cohort study. To validate computed tomography (CT) radiodensity in Hounsfield units (HU) as a prognostic marker for pedicle screw loosening or cage subsidence in minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). The retrospective study involved 198 patients treated with MI-TLIF. Screw loosening (SL), cage subsidence (CS), and fusion status were assessed by plain radiographs. The risk factors of SL and CS were identified using logistic regression. A total of 258 levels and 930 screws were analyzed. During a 2-year follow-up, 16.2% and 24.7% of patients had CS and SL respectively. The cut-off value of L1 HU for predicting SL or CS was 117. The L1 HU 25 were two independent risk factors that can be screened preoperatively for preventing SL or CS and lead to better management of patients undergoing MI-TLIF.

Activation of neutrophil leukocytes is tightly regulated, and it is important to understand the molecular mechanisms of their response to physiological and pathological stimuli. Here authors show that the adhesion molecule G protein-coupled receptor 97 and its interaction partners play pivotal roles in neutrophil leukocyte activation both in anti-microbial response and in inflammatory diseases.

Abstract Background Deep surgical site infection (DSSI) is one of the most challenging complications in lumbar fusion surgery. Few investigations examined the effect of vancomycin powder mixed with autogenic bone graft (ABG) and bone substitutes on preventing DSSI in degenerative lumbar fusion surgeries as well as any interference with bony fusion. The aim of the study was to investigate the effects of ABG along with bone substitutes as a local vancomycin delivery system on preventing DSSI in lumbar instrumented fusion and compared with those who did not use vancomycin powder. Methods From January, 2015 through December, 2015, a one-year prospective study using vancomycin powder mixed with ABG and bone substitute for degenerative lumbar fusion surgeries as vancomycin (V) group, 1 gm vancomycin for 2 and 3-level, and 2 gm for more than 3-level instrumentation. From December, 2013 through December 2014, patients received degenerative lumbar fusion surgeries without using vancomycin before the vancomycin protocol were retrospectively enrolled as non-vancomycin (NV) group. Vancomycin concentration was checked at post-operative days 1 and 3 for both the serum and drainage. Patients’ demographic data, microbiology reports, fusion status and functional outcomes were evaluated. Results One hundred and ten patients were enrolled prospectively in the V group, and 86 for the NV group. After an average 41 months follow-up (range, 36–54), 3 patients (3.48%) developed postoperative DSSIs in the NV group, thereby requiring revision surgeries and parenteral antibiotics treatment versus no DSSIs (0%, 0/100) in the V group. (p = 0.048). The postoperative serum vancomycin levels were undetectable and no vancomycin related side effects was encountered. The mean vancomycin concentration of drainage at postoperative days 1 and 3 were 517.96 ± 174.4 and 220.14 ± 102.3 μg/mL, respectively. At final follow-up, there was no statistical difference observed in terms of clinical and radiologic outcomes. Conclusions Our vancomycin protocol may reduce the incidence of DSSI in degenerative lumbar fusion surgery without affecting bony fusion. Level of Evidence Level III ambispective comparative study.

Abstract Background Involvement in cervical ligamentum flavum is a rare manifestation of the calcium pyrophosphate dihydrate deposition disease. Only few cases of this condition have been reported. We revealed eighteen cases of CPPD in cervical ligamentum flavum that diagnosed at a single medical center. In our case series, clinical characteristics and magnetic resonance imaging findings of patients are described. Methods We retrospectively reviewed the medical charts and imaging studies of the eighteen patients with pseudogout attack of the cervical ligamentum flavum. In addition, we discussed the differences between this disease and ossification of ligamentum flavum in image manifestations. Results There were fourteen men and four women aged between 59 and 87 years. Diabetes mellitus and hypertension were the most common comorbidities. Myelopathy and neck pain were presented in most patients. C4–5 and C5–6 were attacked most frequently, and multiple- rather than single-level involvement could be observed in our series. “Acute on chronic phenomenon” was a specific magnetic resonance image finding in patients whose symptom durations were between 2 to 5 months. Compared to ossification of ligamentum flavum, calcium pyrophosphate dihydrate crystal deposition had different image signs, including morphology, side of the involved ligament, no continuity with the lamina, acute on chronic phenomenon, and presence of retro-odontoid mass. Conclusions Nodular calcifications in cervical ligamentum flavum raise highly suspicion for calcium pyrophosphate dihydrate deposition and must be diagnosed by histological examination and polarized light microscopy. This disease is different from ossification of ligamentum flavum, and it could be recognized by specific image features.

GPR56/ADGRG1 is a versatile adhesion G protein-coupled receptor important in the physiological functions of the central and peripheral nervous systems, reproductive system, muscle hypertrophy, immune regulation, and hematopoietic stem cell generation. By contrast, aberrant expression or deregulated functions of GPR56 have been implicated in diverse pathological processes, including bilateral frontoparietal polymicrogyria, depression, and tumorigenesis. In this review article, we summarize and discuss the current understandings of the role of GPR56 in health and disease.

Abstract Background With the progress and success in minimally invasive surgery of transforaminal lumbar interbody fusion (MIS TLIF), the musculoskeletal injury was minimized. However, the role of postoperative orthosis in MIS TLIF has not been established and there is little evidence supporting the routine use of orthosis in MIS TLIF. Methods This is a prospective randomized clinical study. 90 patients who underwent MIS TLIF were randomly divided into groups A (with postoperative spinal orthosis) and B (without postoperative spinal orthosis). Patients were followed up for an average of 12.6 months. Clinical outcome was assessed using the Oswestry disability index (ODI) and visual analogue scale (VAS). Fusion rate was classified with the BSF scale system at postoperative 6-month, and 12-month. Results Both groups had similar patient demographics. The use of postoperative spinal orthosis had no significant influence on instrumentation-related complications or radiological parameters at each follow-up. Conclusions In this study, we conclude that postoperative spinal orthosis is not necessary for MIS TLIF. Patients without postoperative spinal orthosis had the same fusion rates and improvement of VAS and ODI scores.

Abstract To evaluate the impact of the preoperative severity of facet joint arthropathy on long-term functional outcomes and spinopelvic parameters in patients undergoing lumbar-stability-preserving decompression and Dynesys fixation. In this retrospective study, 88 patients undergoing combined surgery at our hospital from 2008 to 2015 were included. The patients were divided into two groups, the less and more than mean degeneration groups, based on preoperative facet joint arthropathy of the index level(s). The clinical outcomes were the Visual Analogue Scale (VAS) score, the Oswestry Disability Index (ODI) score and spinopelvic parameters. The mean follow-up durations for the less and more than mean degeneration groups were 84.83 ± 27.58 and 92.83 ± 20.45 months, respectively. The combined surgery significantly improved VAS and ODI scores, and increased sacral slope (SS) regardless of preoperative arthropathy severity. In addition, facet joint arthropathy at adjacent levels continued to worsen after surgery in both arthropathy severity groups. Preoperative facet joint arthropathy did not influence most long-term clinical outcomes in patients undergoing lumbar-stability-preserving decompression and Dynesys fixation. This combined surgery may be suitable for patients with facet joint arthropathy regardless of disease severity.

Abstract Background Safe placement of pedicle screws without jeopardizing neurovascular structures medially and anteriorly is important during spine surgery. Inferior breach of pedicle is also dangerous due to low margin of error. Lumbar morphology and identical pedicle orientation at L1 to L5 shown on CT scan of young Taiwanese patients (90 patients) were analyzed and compared with findings reported for Caucasian subjects. Methods Previously reported techniques were employed to quantitatively elucidate the parameters regarding lumbar morphology and identical pedicle orientation at each vertebra. The parameters for pedicle angle (PA), pedicle diameter (PD), pedicle axis distance (PAD), midline axis distance (MAD), transverse pedicle axis distance (TPAD) and transverse intertangential angle (TITA) were measured. Results Taiwanese subjects had different PA, PD, PAD, MAD at L1 to L5 and TITA at L3 to L5 compared with Caucasian subjects. L5 had the most convergent pedicle axis, the widest PD and the shortest antero-posterior axis morphology. Conclusions This study provides detailed information for identifying pedicle orientation during pedicle screw placement and elucidate racial differences in lumbar morphology and pedicle orientation between Taiwanese and Caucasian populations.

This study aimed to compare the accuracy of navigation-assisted percutaneous pedicle screw insertions between traditional posterior superior iliac spine (PSIS) fixed and cutaneously fixed dynamic reference frame (DRF) in minimally invasive surgery of transforaminal lumbar interbody fusion (MIS TLIF). This is a prospective randomized clinical study. Between May 2016 and Nov 2017, 100 patients who underwent MIS TLIF were randomly divided into bone fixed group (with PSIS fixed DRF) and skin fixed group (with cutaneously fixed DRF). The pedicel screws were inserted under navigational guidance using computed tomography (CT) data acquired intraoperatively with a Ziehm 3-dimensional fluoroscopy-based navigation system. Screw positions were immediately checked by a final intraoperative scan. The accuracy of screw placement was evaluated by a sophisticated computed tomography protocol. Both groups had similar patient demographics. Totally Five-hundred Twelve pedicle screws were placed in the lumbar spine. There were 2 moderate (2–4 mm) pedicle perforations in each group. The accuracy showed no significant difference between bone fixed and skin fixed DRF. There were no significant procedure-related complications. The skin fixed DRF provides similar accuracy in pedicle screw insertions with bone fixed DRF using intraoperative 3D image guided navigation in MIS TLIF. Skin fixed DRF not only serves as an alternative method but also saves a separate incision wound for bony attachment.

EMR2/ADGRE2 is an adhesion G protein-coupled receptor differentially expressed by human myeloid cells. It modulates diverse cellular functions of innate immune cells and a missense EMR2 variant is directly responsible for vibratory urticaria. Recently, EMR2 was found to activate NLRP3 inflammasome in monocytes via interaction with FHR1, a regulatory protein of complement Factor H. However, the functional involvement of EMR2 activation and its signaling mechanisms in eliciting NLRP3 inflammasome activation remain elusive. In this study, we show that EMR2-mediated signaling plays a critical role in triggering the activation (2nd) signal for the NLRP3 inflammasome in both THP-1 monocytic cell line and primary monocytes. Stimulation of EMR2 by its agonistic 2A1 monoclonal antibody elicits a Gα16-dependent PLC-β activation pathway, inducing the activity of downstream Akt, MAPK, NF-κB, and Ca2+ mobilization, eventually leading to K+ efflux. These results identify EMR2 and its associated signaling intermediates as potential intervention targets of NLRP3 inflammasome activation in inflammatory disorders.

Background/objectiveHigh tibial osteotomy (HTO) is a common treatment for medial knee arthrosis. However, a high rate of complications associated with a plate and a significant loss of correction have been reported. Therefore, an internal support block (ISB) is designed to enhance the initial stability of the fixation device that is important for successful bone healing and maintenance of the correction angle of the osteotomy site. The purpose of this study was performed to examine if an internal support block combined with a plate reduces the stress on the plate and screw area.MethodsFinite element models were reconstructed following three different implant combinations. Two loading conditions were applied to simulate standing and initial sit-to-stand postures. Data analysis was conducted to evaluate the axial displacement of the posteromedial tibial plateau, which represents the loss of the posteromedial tibial plateau in clinical observation. Moreover, the stresses on the bone plate and locking screws were evaluated.ResultsCompared to the TomoFix plate, the ISB reduced the axial displacement by 73% and 76% in standing and initial sit-to-stand loading conditions, respectively. The plate with an ISB reduced stress by 90% on the bone plate and by 73% on the locking screw during standing compared to the standalone TomoFix plate. During the initial sit-to-stand loading condition, the ISB reduced the stress by 93% and 77% on the bone plate and the locking screw, respectively.ConclusionThe addition of the PEEK block showed a benefit for structural stability in the osteotomy site. However, further clinical trials are necessary to evaluate the clinical benefit of reduced implant stress and the internal support block on the healing of the medial bone tissue.

FAM46A belongs to the FAM46 subfamily of the nucleotidyltransferase-fold superfamily and is predicted to be a non-canonical poly(A) polymerase. FAM46A has been linked to several human disorders including retinitis pigmentosa, bone abnormality, cancer, and obesity. However, its molecular and functional characteristics are largely unknown. We herein report that FAM46A is expressed in cells of the hematopoietic system and plays a role in hemin-induced hemoglobinization. FAM46A is a nucleocytoplasmic shuttle protein modified by Tyr-phosphorylation only in the cytosol, where it is closely associated with ER. On the other hand, it is located proximal to the chromatin regions of active transcription in the nucleus. FAM46A is a cell cycle-dependent poly-ubiquitinated short-lived protein degraded mostly by proteasome and its overexpression inhibits cell growth and promotes hemin-induced hemoglobinization in K562 cell. Site-directed mutagenesis experiments confirm the non-canonical poly(A) polymerase activity of FAM46A is essential for enhanced hemin-induced hemoglobinization. In summary, FAM46A is a novel poly(A) polymerase that functions as a critical intracellular modulator of hemoglobinization.

Cells respond to diverse types of mechanical stimuli using a wide range of plasma membrane-associated mechanosensitive receptors to convert extracellular mechanical cues into intracellular signaling. G protein-coupled receptors (GPCRs) represent the largest cell surface protein superfamily that function as versatile sensors for a broad spectrum of bio/chemical messages. In recent years, accumulating evidence has shown that GPCRs can also engage in mechano-transduction. According to the GRAFS classification system of GPCRs, adhesion GPCRs (aGPCRs) constitute the second largest GPCR subfamily with a unique modular protein architecture and post-translational modification that are well adapted for mechanosensory functions. Here, we present a critical review of current evidence on mechanosensitive aGPCRs.

Background: GPR56/ADGRG1 is a member of the adhesion-class G protein-coupled receptor (aGPCR) family important in brain development, oncogenesis and tumor metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site (GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF). Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the underlying mechanism and its pathophysiologic role remains undetermined. Objective: To assess the presence of sGPR56 in human serum using ELISA assay and compare the serum sGPR56 levels among patients of various chronic inflammatory diseases and healthy subjects. Patients and methods: In this study, serum samples from patients with systemic lupus erythematosus (SLE) (n = 57), rheumatoid arthritis (RA) (n = 95), Sjögren's syndrome (SS) (n = 29), ankylosing spondylitis (AS) (n = 51), and normal controls (n = 81) were analyzed using sGPR56-specific ELISA. Result: We show that serum sGPR56 levels are increased in patients of RA, but not in those with SLE, SS and AS. Intriguingly, serum sGPR56 levels in RA patients correlated with positive rheumatoid factor, a marker of bone erosion and poor outcome. In addition, an elevated sGPR56 level is also noted in RA patients with higher tumor necrosis factor level. Conclusion: we conclude that sGPR56 is present in vivo and sGPR56 level is elevated in certain chronic inflammatory diseases such as RA. Hence, sGPR56 might be considered a potential biomarker for RA disease progression. Keywords: Adhesion-GPCR, Biomarker, sGPR56, Shedding, RA

Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. We summarize herein the latest findings of the role of ADGRG1/GPR56 in tumor progression.

Abstract Patients with pneumonia and parapneumonic effusion (PPE) have elevated mortality and a poor prognosis. The aim of this study was to discover novel biomarkers to help distinguish between uncomplicated PPE (UPPE) and complicated PPE (CPPE). Using an iTRAQ-based quantitative proteomics, we identified 766 proteins in pleural effusions from PPE patients. In total, 45 of these proteins were quantified as upregulated proteins in CPPE. Four novel upregulated candidates (BPI, NGAL, AZU1, and calprotectin) were selected and further verified using enzyme-linked immunosorbent assays (ELISAs) on 220 patients with pleural effusions due to different causes. The pleural fluid levels of BPI, NGAL, AZU1, and calprotectin were significantly elevated in patients with CPPE. Among these four biomarkers, BPI had the best diagnostic value for CPPE, with an AUC value of 0.966, a sensitivity of 97%, and a specificity of 91.4%. A logistic regression analysis demonstrated a strong association between BPI levels > 10 ng/ml and CPPE (odds ratio = 341.3). Furthermore, the combination of pleural fluid BPI levels with LDH levels improved the sensitivity and specificity to 100% and 91.4%, respectively. Thus, our findings provided a comprehensive effusion proteome data set for PPE biomarker discovery and revealed novel biomarkers for the diagnosis of CPPE.

Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing. GPR56 pursues this activity by associating with the tetraspanin CD81. We conclude that GPR56 inhibits natural cytotoxicity of human NK cells.

The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members in human, several of which are distinctly expressed and functionally involved in polymorphonuclear cells (PMNs). As former work indicated the possible presence of the aGPCR GPR97 in granulocytes, we studied its cellular distribution, molecular structure, signal transduction, and biological function in PMNs. RNA sequencing and mass-spectrometry revealed abundant RNA and protein expression of ADGRG3/GPR97 in granulocyte precursors and terminally differentiated neutrophilic, eosinophilic, and basophilic granulocytes. Using a newly generated GPR97-specific monoclonal antibody, we confirmed that endogenous GPR97 is a proteolytically processed, dichotomous, N-glycosylated receptor. GPR97 was detected in tissue-infiltrating PMNs and upregulated during systemic inflammation. Antibody ligation of GPR97 increased neutrophil reactive oxygen species production and proteolytic enzyme activity, which is accompanied by an increase in mitogen-activated protein kinases and IκBα phosphorylation. In-depth analysis of the GPR97 signaling cascade revealed a possible switch from basal Gαs/cAMP-mediated signal transduction to a Gαi-induced reduction in cAMP levels upon mutation-induced activation of the receptor, in combination with an increase in downstream effectors of Gβγ, such as SRE and NF-κB. Finally, ligation of GPR97 increased the bacteria uptake and killing activity of neutrophils. We conclude that the specific presence of GPR97 regulates antimicrobial activity in human granulocytes.

Adhesion G protein-coupled receptors (aGPCRs) constitute the second largest GPCR subfamily. GPR56/ADGRG1 is a member of the ADGRG subgroup of aGPCRs. Although GPR56 is best known for its pivotal role in the cerebral cortical development, it is also important for tumor progression. Numerous studies have revealed that GPR56 is expressed in various cancer types with a role in cancer cell adhesion, migration and metastasis. In a recent study, we found that the immobilized GPR56-specific CG4 antibody enhanced IL-6 production and migration ability of melanoma cells. In this review, we will summarize the current understanding of GPR56 function and discuss the activation and signaling mechanisms of GPR56 in melanoma cells.

G-protein-coupled receptors (GPCRs) are seven transmembrane cell surface proteins specialized in cellular communication. These receptors represent a major gateway through which cells convert external cues into intracellular signals and respond with appropriate actions. While the effects of hormones, neurotransmitters, and drugs on cells, tissues, organs, and even whole organisms are well described, the molecular identity of the direct targets and the diverse signaling mechanisms of these biological ligands have been slow and hard to define. The Nobel Prize in Chemistry for the year 2012 acknowledges the importance of GPCRs in these processes, especially for the contribution of Profs Robert J. Lefkowitz and Brian K. Kobilka to the studies of GPCRs. In this brief review, the seminal works accomplished by the two GPCR pioneers are summarized and the (bio) chemical significance of GPCRs in health and disease is discussed.

Higher soluble CD4 (sCD4) levels in serum have been detected in patients of infectious and chronic inflammatory diseases. However, how and why sCD4 is produced remains poorly understood. We establish sensitive ELISA and WB assays for sCD4 detection in conditioned medium of in vitro cell culture system and serum of chronic inflammatory patients. Serum samples from patients with systemic lupus erythematosus (SLE) (n = 79), rheumatoid arthritis (RA) (n = 59), ankylosing spondylitis (AS) (n = 25), gout (n = 31), and normal controls (n = 99) were analyzed using ELISA for sCD4 detection. Results from each assay were analyzed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups. We confirm that cells expressing exogenous CD4 produce sCD4 in a constitutive and PMA-induced manner. Importantly, sCD4 production in a heterologous expression system is inhibited by GM6001 and TAPI-0, suggesting receptor shedding by matrix metalloproteinase (MMP)-like proteinases. Moreover, similar findings are recapitulated in human primary CD4(+) T cells. Finally, we show that serum sCD4 levels are increased in patients of chronic inflammatory diseases including RA and SLE, but not in those with gout. Intriguingly, sCD4 levels in RA patients are correlated positively with the disease activities and higher sCD4 levels seem to associate with poor prognosis. Taken together, we conclude that CD4 is shed from cell surface by a MMP-like sheddase and sCD4 level is closely related with the inflammatory condition in certain chronic diseases. Hence, sCD4 might be considered an important parameter for RA disease progression with potential diagnostic importance.

Background: The dynamic Dynesys Stabilization System preserves lumbar mobility at instrumented levels. This study investigated the effect of screw length on screw loosening (SL) after dynamic Dynesys fixation and screw displacement during lumbar motion, using clinical investigation and finite-element (FE) analysis. Methods: Clinical data of 50 patients with degenerative spondylolisthesis treated with decompression and Dynesys fixation in 2011 were analyzed retrospectively. Horizontal sliding displacement and vertical displacement of screw tips at L4 were analyzed postoperatively using displacement-controlled FE analysis at the L4-L5 level with screw lengths 45 (long screw), 36 (median screw), and 27 (short screw), and 6.4 mm in diameter, under flexion, extension, lateral bending, and rotation. Results: In 13 patients (13/50, 26%), 40 screws (40/266, 15%) were loose at mean follow-up of 101.3 ± 4.4 months. Radiographic SL at 35, 40, 45, and 50 mm were 7.7%, 10.7%, 12.1%, and 37.5%, respectively, regardless of the fixation level (p = 0.009). FE analysis revealed that the long screw model with corresponding longer lever arm had maximal horizontal sliding displacement under all directions and maximal vertical displacement, except for lateral bending. Conclusion: Shorter screws in Dynesys fixation may help avoid dynamic SL. Clinically, 50 mm screws showed the greatest SL and median screw screws demonstrated the least displacement biomechanically. [ABSTRACT FROM AUTHOR]

Background: Postvertebroplasty infection (PVI) is a catastrophic complication after vertebroplasty (VP). Although the urinary tract has been considered as a source of infectious pathogens, whether asymptomatic bacteriuria (ASB) is a risk factors for PVI remains unknown. Methods: This retrospective study included 716 patients (207 males; 509 females) treated with VP for osteoporotic vertebral fractures in a single medical center between May 2015 and December 2019. Clinical symptoms, urinalysis results, and culture data were collected preoperatively to identify patients with ASB. The primary outcome was PVI at the index level during follow-up. Demographic data and laboratory test results were compared between the PVI and non-PVI groups. Results: The mean age of the cohort was 78.6 ± 9.6 (range, 63-106). The prevalence of ASB was 14.1%, with female predominance (63.4%). The overall PVI rate was 1.26% (9/716). The PVI group had more patients with ASB (4/9, 44.4%) than did the non-PVI group (97/707, 13.7%) (p = 0.027). The rate of ASB treatment was similar between the PVI and non-PVI groups (25% vs. 23.7%, respectively). No case of PVI was caused by the urine culture pathogen. Multivariate analysis identified the following risk factors for PVI: ASB (odds ratio [OR], 5.61; 95% CI, 1.14-27.66; p = 0.034), smoking (OR, 16.26; 95% CI, 2.58-102.65; p = 0.003), and malignancy (OR 7.27; 95% CI, 1.31-40.31; p = 0.023). Conclusion: ASB was not uncommon among patients admitted for VP and should be considered a marker of relatively poor host immunity. Preoperative ASB, a history of malignancy, and smoking were identified as significant risk factors for PVI. [ABSTRACT FROM AUTHOR]