Functional partnerships between GPI-anchored proteins and adhesion GPCRs.

Specific extracellular interaction between glycophosphatidylinositol (GPI)-anchored proteins and adhesion G protein-coupled receptors (aGPCRs) plays an important role in unique biological functions. GPI-anchored proteins are derived from a novel post-translational modification of single-span membrane molecules, while aGPCRs are bona fide seven-span transmembrane proteins with a long extracellular domain. Although various members of the two structurally-distinct protein families are known to be involved in a wide range of biological processes, many remain as orphans. Interestingly, accumulating evidence has pointed to a complex interaction and functional synergy between these two protein families. I discuss herein current understanding of specific functional partnerships between GPI-anchored proteins and aGPCRs.

Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis.

Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.

Proteinase 3 promotes formation of multinucleated giant cells and granuloma-like structures in patients with granulomatosis with polyangiitis.

OBJECTIVES: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target proteinase 3 (PR3) or myeloperoxidase (MPO) found within neutrophils and monocytes. Granulomas are exclusively found in GPA and form around multinucleated giant cells (MGCs), at sites of microabscesses, containing apoptotic and necrotic neutrophils. Since patients with GPA have augmented neutrophil PR3 expression, and PR3-expressing apoptotic cells frustrate macrophage phagocytosis and cellular clearance, we investigated the role of PR3 in stimulating giant cell and granuloma formation. METHODS: We stimulated purified monocytes and whole peripheral blood mononuclear cells (PBMCs) from patients with GPA, patients with MPA or healthy controls with PR3 or MPO and visualised MGC and granuloma-like structure formation using light, confocal and electron microscopy, as well as measuring the cell cytokine production. We investigated the expression of PR3 binding partners on monocytes and tested the impact of their inhibition. Finally, we injected zebrafish with PR3 and characterised granuloma formation in a novel animal model. RESULTS: In vitro, PR3 promoted monocyte-derived MGC formation using cells from patients with GPA but not from patients with MPA, and this was dependent on soluble interleukin 6 (IL-6), as well as monocyte MAC-1 and protease-activated receptor-2, found to be overexpressed in the cells of patients with GPA. PBMCs stimulated by PR3 formed granuloma-like structures with central MGC surrounded by T cells. This effect of PR3 was confirmed in vivo using zebrafish and was inhibited by niclosamide, a IL-6-STAT3 pathway inhibitor. CONCLUSIONS: These data provide a mechanistic basis for granuloma formation in GPA and a rationale for novel therapeutic approaches.

Role of Adhesion G Protein-Coupled Receptors in Immune Dysfunction and Disorder.

Disorders of the immune system, including immunodeficiency, immuno-malignancy, and (auto)inflammatory, autoimmune, and allergic diseases, have a great impact on a host's health. Cellular communication mediated through cell surface receptors, among different cell types and between cell and microenvironment, plays a critical role in immune responses. Selective members of the adhesion G protein-coupled receptor (aGPCR) family are expressed differentially in diverse immune cell types and have been implicated recently in unique immune dysfunctions and disorders in part due to their dual cell adhesion and signaling roles. Here, we discuss the molecular and functional characteristics of distinctive immune aGPCRs and their physiopathological roles in the immune system.

Does local vancomycin powder impregnated with autogenous bone graft and bone substitute decrease the risk of deep surgical site infection in degenerative lumbar spine fusion surgery?-An ambispective study.

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.

Nucleolar control by a non-apoptotic p53-caspases-deubiquitinylase axis promotes resistance to bacterial infection.

The nucleolus is best known for its cellular role in regulating ribosome production and growth. More recently, an unanticipated role for the nucleolus in innate immunity has recently emerged whereby downregulation of fibrillarin and nucleolar contraction confers pathogen resistance across taxa. The mechanism of this downregulation, however, remains obscure. Here we report that rather than fibrillarin itself being the proximal factor in this pathway, the key player is a fibrillarin-stabilizing deubiquitinylase USP-33. This was discovered by a candidate-gene search of Caenorhabditis elegans in which CED-3 caspase was revealed to execute targeted cleavage of USP-33, thus destabilizing fibrillarin. We also showed that cep-1 and ced-3 mutant worms altered nucleolar size and decreased antimicrobial peptide gene, spp-1, expression rendering susceptibility to bacterial infection. These phenotypes were reversed by usp-33 knockdown, thus linking the CEP-1-CED-3-USP-33 pathway with nucleolar control and resistance to bacterial infection in worms. Parallel experiments with the human analogs of caspases and USP36 revealed similar roles in coordinating these two processes. In summary, our work outlined a conserved cascade that connects cell death signaling to nucleolar control and innate immune response.

Postoperative spinal orthosis may not be necessary for minimally invasive lumbar spine fusion surgery: a prospective randomized controlled trial.

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.

Multilevel calcium pyrophosphate dihydrate deposition in cervical ligamentum flavum: clinical characteristics and imaging features.

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.

Functional outcomes and survival after surgical stabilization for inoperable non-small-cell lung cancer with spinal metastasis of the thoracic and lumbar spines: a retrospective comparison between epidermal growth factor receptor-tyrosine kinase inhibitor and platinum-based chemotherapy groups.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the surgical results between targeted therapy and post-operative chemotherapy for patients with spinal metastasis of inoperable non-small-cell lung cancer (NSCLC). SETTING: Single-center study at an academic orthopedic department in Taiwan. METHODS: Sixty-five patients were treated surgically for spinal metastasis of inoperable NSCLC with long posterior instrumentation with or without posterior decompression according to the patient's neurologic status. Post-operative radiotherapy of the spinal lesion and targeted therapy or chemotherapy were done following surgery after the surgical wound healed. Post-operative clinical outcomes and survival were evaluated and compared between these two groups. The overall survival represented survival from the date of diagnosis to death. RESULTS: Thirty-five patients were grouped as the targeted therapy group and 30 patients as the chemotherapy group. The overall median survival times were 12.0 and 10.0 months in the targeted therapy and chemotherapy groups, respectively. Sixty-two patients were able to walk with or without an aid postoperatively. There was no significant difference observed between these two groups in terms of pain relief, neurologic improvement, ambulatory improvement, and survival. CONCLUSIONS: Surgical stabilization with or without laminectomy improved functional outcomes in patients with inoperable non-small-cell lung cancer, and post-operative functional outcomes were similar between chemotherapy and targeted therapy groups. A longer survival was observed with targeted therapy for the patients whose NSCLC was diagnosed before spinal metastasis, however, the longer survival was not statistically significant.

The role of the RGD motif in CD97/ADGRE5-and EMR2/ADGRE2-modulated tumor angiogenesis.

CD97/ADGRE5, an adhesion G protein-coupled receptor (aGPCR), is highly expressed in several tumor cell types. CD97 has been shown to modulate tumorigenesis in part by promoting HUVEC migration, invasion and angiogenesis through the interaction with integrin α5ß1 via its ectodomain RGD motif. In this study, we show that CD97 could induce angiogenesis via an alternative RGD-independent mechanism. Overexpression of CD97 with the wild-type or mutant RGD motif in HT1080 cells led to up-regulated MMP-9 and induced angiogenesis as revealed by the in vitro endothelial cell tube formation assay and in ovo chick chorioallantoic membrane assay. By contrast, expression of EMR2/ADGRE2, the CD97-homologous aGPCR that contains a corresponding SGD sequence, fails to induce angiogenesis due to lower MMP-9 expression. Interestingly, a single change of the SGD to RGD sequence allowed EMR2 to up-regulate MMP-9 expression, leading to enhanced angiogenesis. MMP-9 was shown to promote the proliferation, migration, and invasion of HUVEC partly by modulating the levels of VEGF, PIGF, and bFGF. Finally, we showed that the MMP-9 expression was in turn modulated by N-cadherin that was up-regulated by CD97 and EMR2/RGD. Our results indicate that two homologous aGPCRs, CD97 and EMR2, modulate angiogenesis and HUVEC proliferation, migration, and invasion through N-cadherin-regulated MMP-9 expression by RGD-independent and -dependent mechanisms, respectively.

Differences in the interbody bone graft area and fusion rate between minimally invasive and traditional open transforaminal lumbar interbody fusion: a retrospective short-term image analysis.

PURPOSE: We aimed to quantify the interbody bone graft area following transforaminal lumbar interbody fusion (TLIF) using traditional open and minimally invasive surgeries (MIS) and investigate their correlations with rates of fusion, complications, and clinical outcomes. METHODS: Patients undergoing TLIF of 1 or 2 levels between October 2015 and December 2016 were retrospectively included. Fusion and bone graft areas were assessed with computed tomography (CT) at 6 months postoperatively. The bone graft area ratio was defined as the bone graft area divided by the average endplate area. The distributions of bone graft area within the discs were also recorded. Clinical outcomes were assessed using the visual analog scale (VAS) and Oswestry Disability Index (ODI) questionnaires. RESULTS: In total, 77 disc levels in 57 patients were analyzed. The fusion rate was 79.1% in the open group and 82.4% in the MIS group (p = 0.718). Clinical outcomes of both groups improved significantly. Changes in VAS and ODI scores at 12 months postoperatively were comparable between groups. Bone graft area ratio was not significantly different between the two groups (open, 38 ± 10.8%; MIS, 38.1 ± 9.0%, p = 0.977). Analysis of bone graft distribution revealed that the contralateral-dorsal part of the disc had the lowest bone graft area. The bone graft area ratio was significantly higher in the solid union group (39.2 ± 10.4%) than in the non-solid union group (33.5 ± 6.4%, p = 0.048). CONCLUSIONS: The fusion rates, bone graft area ratios, clinical outcomes, and complications were similar between MIS and open TLIF. These slides can be retrieved under Electronic Supplementary Material.

What is the difference in morphologic features of the lumbar vertebrae between Caucasian and Taiwanese subjects? A CT-based study: implications of pedicle screw placement via Roy-Camille or Weinstein method.

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.

Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility.

GPR56 is an adhesion-class G-protein-coupled receptor responsible for bilateral frontoparietal polymicrogyria (BFPP), a severe disorder of cortical formation. Additionally, GPR56 is involved in biological processes as diverse as hematopoietic stem cell generation and maintenance, myoblast fusion, muscle hypertrophy, immunoregulation and tumorigenesis. Collagen III and tissue transglutaminase 2 (TG2) have been revealed as the matricellular ligands of GPR56 involved in BFPP and melanoma development, respectively. In this study, we identify heparin as a glycosaminoglycan interacting partner of GPR56. Analyses of truncated and mutant GPR56 proteins reveal two basic-residue-rich clusters, R(26)GHREDFRFC(35) and L(190)KHPQKASRRP(200), as the major heparin-interacting motifs that overlap partially with the collagen III- and TG2-binding sites. Interestingly, the GPR56-heparin interaction is modulated by collagen III but not TG2, even though both ligands are also heparin-binding proteins. Finally, we show that the interaction with heparin reduces GPR56 receptor shedding, and enhances cell adhesion and motility. These results provide novel insights into the interaction of GPR56 with its multiple endogenous ligands and have functional implications in diseases such as BFPP and cancer.

TNFR signalling and its clinical implications.

Tumour necrosis factor-α (TNF-α) is a highly pleiotropic cytokine with effects on multiple pathological and physiological functions via two distinct receptors, TNFR1 and TNFR2. Much of the pro- inflammatory action of TNF-α is mediated by TNFR1 whereas TNFR2 is thought to play an immunoregulatory and tissue protective role. Anti-TNF- α biologics have been extremely successful in treating a number of immune mediated pathologies, including rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis and inflammatory bowel disease. However, anti-TNF therapy has been shown to induce systemic lupus erythematosus and psoriasis in some patients, and to be deleterious in multiple sclerosis. It is hypothesized that these paradoxical effects of anti-TNF-α are due to inhibition of TNFR2 signalling. In this review, we will focus on the biology and pathophysiologic role of TNF-α and on the therapeutic implications of targeting TNF-α receptor signalling.

Implantation of an empty polyetheretherketone cage in anterior cervical discectomy and fusion: a prospective randomised controlled study with 2 years follow-up.

PURPOSE: To compare the clinical outcomes, radiographic results and fusion rate of ACDF between empty PEEK cages and PEEK cages packed with ß-tricalcium phosphate. METHODS: Forty-five patients were prospectively enrolled with cervical degenerative disc disease who requiring ACDF with a PEEK cage. 23 patients were randomised to the study group (empty cages) and 22 patients were in the control group (cages filled with ß-tricalcium phosphate). Both patient groups were fixed with a cervical locking plate. A CT scan was performed 12 months postoperatively and 24 months if not confirmed fused at 12 months to evaluate the status of fusion. Clinical status was evaluated using the Japanese Orthopaedic Association (JOA) score, the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS). RESULTS: 46 levels (97.88%) in the study group and 44 levels (97.77%) in the control group were confirmed as fused at 24 months. There was no significant difference between the fusion rates observed in the study and control groups (p = 0.82). There was no significant difference in JOA, ODI, or VAS scores at 24 months follow-up. The results showed that the members of the non-fusion group tended to be older than the individuals in the fusion group at 12 months, but was not significant in statistics. CONCLUSIONS: Similar fusion rates and clinical outcomes were achieved when using ACDF with PEEK cages and instrumentation, regardless of whether the cage was filled with bone substitute at 24 months follow-up. Fusion rates improved over time and are comparable between both groups. These slides can be retrieved under Electronic Supplementary material.

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.

The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein-coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential.

The fates of pedicle screws and functional outcomes in a geriatric population following polymethylmethacrylate augmentation fixation for the osteoporotic thoracolumbar and lumbar burst fractures with mean ninety five month follow-up.

PURPOSE: Polymethylmethacrylate (PMMA) augmentation is a common method to increase pullout strength fixed for osteoporotic spines. However, few papers evaluated whether these pedicle screws migrated with time and functional outcome in these geriatrics following PMMA-augmented pedicle screw fixation. METHODS: From March 2006 to September 2008, consecutive 64 patients were retrospectively enrolled. VAS and ODI were used to evaluate functional outcomes. Kyphotic angle at instrumented levels and horizontal and vertical distances (HD and VD) between screw tip and anterior and upper cortexes were evaluated. To avoid bias, we used horizontal and vertical migration index (HMI and VMI) to re-evaluate screw positions with normalization by the mean of superior and inferior endplates or anterior and posterior vertebral body height, respectively. RESULTS: Forty-six patients with 282 PMMA-augmented screws were analyzed with mean follow-up of 95 months. Nine patients were further excluded due to bed-ridden at latest follow-up. Twenty-six females and 11 males with mean T score of - 2.7 (range, - 2.6 to - 4.1) and mean age for operation of 77.6 ± 4.3 years (range, 65 to 86). The serial HD and kyphotic angle statistically progressed with time. The serial VD did not statistically change with time (p = 0.23), and neither HMI nor VMI (p = 0.772 and 0.631). Pre-operative DEXA results did not correlate with kyphotic angle. Most patients (80.4%) maintained similar functional outcomes at latest follow-up. The incidence of screws loosening was 2.7% of patients and 1.4% of screws, respectively. The overall incidences of systemic post-operative co-morbidities were 24.3% with overall 20.2 days for hospitalization. CONCLUSION: Most patients (80%) remained similar functional outcomes at latest follow-up in spite of kyphosis progression. The incidence of implant failure was not high, but the post-operative systemic co-morbidities were higher, which has to be informed before index surgery.

Is a drain tube necessary for minimally invasive lumbar spine fusion surgery?

PURPOSE: This study aimed to evaluate if closed suction wound drainage is necessary in minimally invasive surgery of transforaminal lumbar interbody fusion (MIS TLIF). METHODS: This is a prospective randomized clinical study. Fifty-six patients who underwent MIS TLIF were randomly divided into groups A (with a closed suction wound drainage) and B (without tube drainage). Surgical duration, intraoperative blood loss, timing of ambulation, length of hospital stay and complications were recorded. Patients were followed up for an average of 25.3 months. Clinical outcome was assessed using the Oswestry disability index and visual analogue scale (VAS). Fusion rate was classified with the Bridwell grading system, based on plain radiograph. RESULTS: Both groups had similar patient demographics. The use of drains had no significant influence on perioperative parameters including operative time, estimated blood loss, length of stay and complications. Patients in group B started ambulation 1 day earlier than patients in group A (p < 0.001). Clinical outcomes were comparable between group A and group B. CONCLUSION: A drain tube can lead to pain, anxiety and discomfort during the postoperative period. We conclude that drain tubes are not necessary for MIS TLIF. Patients without drains had the benefit of earlier ambulation than those with drains.

CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities.

Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been reported to lead to antigen-specific immunotolerance in allograft transplantation and autoimmune diabetes, as well as possibly to inhibition of allergic inflammation in mice. However, the molecular mechanisms underlying hyporesponsive T cell responses induced by YTS177 MoAb remain elusive. Herein, we demonstrate that the YTS177 MoAb increases the levels of anergy factors p27(kip1) and Cbl-b, inhibits IL-2 production, and impairs calcium mobilization in activated T cells in vitro. YTS177 MoAb suppresses OVA-driven proliferation of DO11.10 CD4(+) T cells in vivo as well. Mechanistically, YTS177 MoAb induces tolerance by causing CD4 down-regulation through clathrin-dependent and raft dissociation. The results obtained in this study lead us to propose novel protective or curative approaches to CD4 T cell-mediated diseases.