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1.
Spine J ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38365006

RESUMO

BACKGROUND CONTEXT: No method currently exists for MRI-based determination of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine using objective criteria. PURPOSE: The purpose of this study was to develop an MRI-based score to determine whether a lesion represents a cervical OPLL lesion and to establish the objective diagnostic value. STUDY DESIGN: Retrospective cohort in a single medical institution. PATIENT SAMPLE: Thirty-five patients undergoing surgery for OPLL (Group A) and 99 patients undergoing cervical disc arthroplasty for soft disc herniation (Group B) between 2011 and 2020 were retrospectively included. All OPLL lesions on unenhanced MRI scan were correlated with a corresponding CT scan. Demographics were comparable between the two groups. OUTCOME MEASURES (PHYSIOLOGIC MEASURES): Using unenhanced magnetic resonance imaging (MRI), the T1- and T2- lesion quality (LQ) scores were calculated. Receiver operating characteristic (ROC) analysis was performed to calculate the area-under-the-curve (AUC) of both LQ scores as a predictor of the presence of OPLL. Computed tomography- (CT-) based Hounsfield unit (HU) values of OPLL lesions were obtained and compared with both LQ scores. The LQ scores for MRI scanners from different manufacturers were compared using Student's t test to confirm the validity of the LQ score by scanner type. METHODS: The regions of interest for signal intensity (SI) were defined as the darkest site of the lesion and the cerebrospinal fluid (CSF) at the cerebellomedullary cistern. The T1 and T2 LQ scores were measured as the ratio of the SI at the darkest site of the lesion divided by the SI of the CSF. RESULTS: The T1 and T2 LQ scores in Group A were significantly lower than those in Group B (p < 0.001). ROC analysis determined that T1 and T2 LQ scores of 0.46 and 0.07, respectively, could distinguish the presence of OPLL with an accuracy of 0.93 and 0.89, respectively (p<.001). When the T1 LQ score of the lesion is <0.46, a diagnosis of OPLL may be suspected with 100% sensitivity and 92.3% specificity. The HU of the lesion had a moderate negative correlation with the T1 LQ score (r=-0.665, p<.0001). Both LQ scores were unaffected by manufacturer type. CONCLUSIONS: This study found a correlation between the MRI-based T1 LQ scores and CT-based HU value for identifying OPLL lesions. Additional studies will be needed to validate that the T1 LQ score from the unenhanced MRI scan can identify cervical OPLL.

2.
J Chin Med Assoc ; 86(11): 985-990, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37729608

RESUMO

BACKGROUND: This prospective randomized controlled study compares the clinical and radiological outcomes between reduction methods with or without compact trabecular bone during percutaneous kyphoplasty in osteoporotic vertebral fractures. METHODS: The cohort of 100 patients who underwent percutaneous kyphoplasty was randomly divided into group A (guide pin and balloon introduced directly into fracture site) and group B (guide pin and balloon inserted away fracture site). The surgery duration, clinical and radiological outcomes postoperatively and at follow-up, and complications of cement leakage and adjacent fracture were recorded. Patients were followed up for an average of 20.18 months. The clinical outcomes were assessed using the Oswestry Disability Index and visual analog scale. RESULTS: The two groups had similar patient demographics, surgery times, and volume of cement injected. The method using elevation of the collapsed endplate indirectly had no significant influence on radiological outcomes but significantly decreased the occurrence of intradiscal cement leakage and improved 1- and 12-month postoperative functional outcomes. CONCLUSION: Elevating and reinforcing the collapsed endplate rather than just filling the defect during percutaneous kyphoplasty is safe and effective. This technique decreased pain and improved function with lower rates of further collapse of the osteoporotic vertebrae compared to defect-filling alone.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/complicações , Fraturas por Compressão/cirurgia , Estudos Prospectivos , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento , Coluna Vertebral , Cimentos Ósseos/uso terapêutico , Fraturas por Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos
3.
Bioessays ; 45(10): e2300115, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37526334

RESUMO

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.


Assuntos
Receptores Acoplados a Proteínas G , Transdução de Sinais , Adesão Celular , Receptores Acoplados a Proteínas G/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Ligadas por GPI
5.
Spine J ; 23(11): 1580-1585, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37473810

RESUMO

BACKGROUND CONTEXT: Surgical site infection (SSI) following lumbar surgery can increase healthcare costs and lead to poor clinical outcome. Irrigation of wounds with saline solution is widely accepted globally and safe for nearly all kinds of surgery. However, the efficacy of different volumes of wound irrigation has not been addressed in elective spine surgery. The role and the optimal amount of intraoperative wound saline irrigation in preventing SSI in clean spinal surgery remain unclear. PURPOSE: We aimed to investigate if insufficient intraoperative irrigation may be a risk factor for postoperative SSI. Additionally, we investigated the optimal amount of normal saline (NS) for irrigation to prevent postoperative SSI. STUDY DESIGN: This is a retrospective study of patients with degenerative spinal stenosis who were treated surgically. Patients were grouped according to the amount of intra-wound irrigation during surgery. PATIENT SAMPLE: We included 444 patients with degenerative lumbar spinal conditions who had undergone one to five level open spinal fusion surgeries from January 2015 through April 2020. OUTCOME MEASURES: The definition of superficial or deep SSI in this study was based on the Centers for Disease Control and Prevention criteria for SSI. The fusion status accessed was based on the Bridwell grading system at the final follow-up. Self-reported and clinical outcome measures include visual analog scale and Oswestry Disability Index. METHODS: A total of 193 patients underwent irrigation with a bulb syringe with manual method (B group) with 2,000 mL NS; 251 patients underwent interpulse battery-powered device irrigation (P group) with >6,000 mL NS. Based on our protocolized departmental guidelines, all patients received the same preoperative preparation and standard surgical steps and postoperative care plan. Patients' demographic and surgical parameters were recorded. The main outcome measures included superficial wound infection, deep infection and overall infection. RESULTS: The incidence of overall SSI was 4.66% in the B group and 1.59% in the P group. The univariate analysis revealed a significant correlation with DM and irrigation amount per hour during surgery but not age, BMI, smoking, operative duration, fusion level, or blood loss. We determined the optimal irrigation amount during surgery as 1,400 mL per hour based on the receiver operating characteristic (ROC) curve (sensitivity, 92.3%; specificity, 44.1%). This was statistically significant (p=.033) with an odds ratio of 9.284 (95% confidence interval 1.2-72.0). In the analysis of surgical factors, the infection group had a significantly lower irrigation amount during surgery. To summarize, patients with diabetes and those receiving less than 1,400 mL of NS/hour had a higher likelihood of developing SSI. CONCLUSIONS: We observed that diabetes and lower volume of intraoperative irrigation were both risk factors for postoperative SSI following degenerative lumbar spine surgery. To reduce SSI in lumbar spine surgery, intra-wound irrigation with more than 1,400 mL/h of NS was recommended.

6.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982575

RESUMO

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.


Assuntos
Neoplasias , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Adesão Celular , Microambiente Tumoral
7.
World Neurosurg ; 173: e629-e638, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36871649

RESUMO

OBJECTIVES: To identify cage and end plate factors of cage subsidence (CS) in patients who underwent oblique lateral interbody fusion (OLIF) and their association with patient-reported outcomes. METHODS: Sixty-one patients (43 women and 18 men), with a total of 69 segments (138 end plates) which underwent OLIF at a single academic institution between November 2018 and November 2020, were included. All the end plates were separated into CS and nonsubsidence groups. Cage-related parameters (cage height, cage width, cage insertion level, and cage position) and end plate-related parameters (position of end plate, Hounsfield unit value of the vertebra, end plate concave angle [ECA], end plate injury, and angular mismatch measured with cage/end plate angle [C/EA]) were compared and analyzed using logistic regression to predict CS. Receiver operating characteristic curve analysis was used to determine the cutoff points of the parameters. RESULTS: Postoperative CS was identified in 50 of the 138 end plates (36.2%). The CS group had significantly lower mean Hounsfield unit values of the vertebra, higher rate of end plate injury, lower ECA, and higher C/EA than the nonsubsidence group. ECA and C/EA were identified as independent risk factors for developing CS. The optimal cutoff points for ECA and C/EA were 176.9° and 5.4°, respectively. CONCLUSIONS: An ECA greater than 176.9° and a cage/end plate angular mismatch greater than 5.4° were found to be independent risk factors of postoperative CS after the OLIF procedure. These findings aid in preoperative decision-making and intraoperative technical guidance.


Assuntos
Vértebras Lombares , Fusão Vertebral , Masculino , Humanos , Feminino , Vértebras Lombares/cirurgia , Placas Ósseas , Fusão Vertebral/métodos , Estudos Retrospectivos
8.
J Chin Med Assoc ; 86(3): 330-337, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729417

RESUMO

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.


Assuntos
Parafusos Ósseos , Fusão Vertebral , Humanos , Estudos Retrospectivos , Amplitude de Movimento Articular , Rotação , Vértebras Lombares/cirurgia
9.
Ann Rheum Dis ; 82(6): 848-856, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36801813

RESUMO

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.


Assuntos
Granulomatose com Poliangiite , Poliangiite Microscópica , Animais , Mieloblastina , Granulomatose com Poliangiite/tratamento farmacológico , Peixe-Zebra , Interleucina-6 , Leucócitos Mononucleares , Anticorpos Anticitoplasma de Neutrófilos , Granuloma/complicações , Células Gigantes , Peroxidase
10.
J Chin Med Assoc ; 86(4): 431-439, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36661286

RESUMO

BACKGROUND: Cement-augmented pedicle screws (CPS) and hybrid construct (HC), consisting of pedicle screws and additional hooks, are common fixation methods for osteoporotic spine fracture. No study has compared surgical results of CPS and HC for treating osteoporotic spine fracture. The aim of the study was to compare surgical results using CPS or HC for osteoporotic fractures of the thoracic or lumbar spine. METHODS: This retrospective cohort study included 84 patients who received surgical treatment with CPS (n = 43) or HC (n = 41) for osteoporotic spine fractures from January 2011 to December 2015, with a mean follow-up of 67 months. Sixty-five patients with neurological deficits received long posterior instrumentation, short posterior decompression, and posterolateral fusion. The 19 patients without neurologic deficits received long posterior instrumentation without posterior decompression and fusion. Radiographic, clinical, and neurologic outcomes were evaluated. RESULTS: The HC group had significantly shorter operative times (231 vs 258 minutes), greater blood loss (497 vs 427 mL), better immediate postoperative kyphosis reduction (10.6° vs 9.1°), and greater final reduction loss (9.8° vs 7.1°) than the CPS group. In both groups, significant loss of the kyphotic angle was apparent during follow-up. Improved ambulation after surgery occurred in 51.2% and 58.5% of patients in the CPS and HC groups, respectively. Neurologic function after surgery improved 0.5 and 0.7 grades in the CPS and HC groups, respectively. Implants failed in 2.3% and 2.4% of patients in the CPS and HC groups, respectively. The incidence of cement leakage from screw augmentation was 38.9%. CONCLUSION: The CPS and HC techniques for treating osteoporotic fractures of the thoracic or lumbar spine did not differ statistically in terms of improved radiologic and clinical outcomes, final neurologic and ambulatory function, or implant failure rates, making them equally comparable alternatives.


Assuntos
Fraturas por Osteoporose , Parafusos Pediculares , Fraturas da Coluna Vertebral , Fusão Vertebral , Humanos , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Lombares/cirurgia , Cimentos Ósseos/uso terapêutico , Resultado do Tratamento
11.
J Chin Med Assoc ; 86(2): 233-239, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36652570

RESUMO

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.


Assuntos
Bacteriúria , Infecções Urinárias , Masculino , Humanos , Feminino , Bacteriúria/etiologia , Bacteriúria/diagnóstico , Bacteriúria/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/diagnóstico , Fumar
12.
Sci Rep ; 13(1): 1620, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709341

RESUMO

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 < 117 and BMI ≥ 25 were two independent risk factors. The risk of SL or CS was 4.1 fold in patients L1 HU < 117 and 2.6 fold in patients with BMI ≥ 25. For patients concurrently having BMI ≥ 25 and pre-op L1 HU < 117, the risk was 4.3 fold. Fusion rate and clinical outcome were comparable in patients with SL or CS. L1 HU < 117 and BMI > 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.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Global Spine J ; 13(2): 472-478, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33733888

RESUMO

STUDY DESIGN: Retrospective case-control study. OBJECTIVES: This study aims to present the clinical and radiographical outcomes of the titanium-polyetheretherketone (Ti/PEEK) composite cage compared to those of the standard PEEK cage in patients receiving minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). METHODS: Patients receiving 1 level MI-TLIF between October 2015 and October 2017 were included with a minimum of 2-year follow-up. The patients were segregated into 2 groups; Ti/PEEK group and PEEK group. Each patient was propensity-matched using preoperative age, sex, and body mass index. Early fusion rate was evaluated by computed tomography at postoperative 6 months. Clinical outcomes were assessed using the visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. RESULTS: After matching, there were 27 patients included in each group. The demographics, diagnosis, and surgical details were not significantly different between the 2 groups. The 6-month rate was 88.9% in Ti/PEEK group. The fusion rate and cage subsidence rate had no difference between the 2 groups. The complication rate in the Ti/PEEK group was comparable to that in the PEEK group. There was no difference in VAS and ODI scores during a 2-year follow-up period. CONCLUSIONS: The use of Ti/PEEK composite cage was as safe and effective as the use of PEEK cage in MI-TLIF. The 6-month fusion rate was 88.9%. Our finding revealed comparable clinical results for surgeons using Ti/PEEK composite cages in MI-TLIF compared to those using the PEEK cage.

14.
J Chin Med Assoc ; 86(1): 113-121, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35904575

RESUMO

BACKGROUND: Superior facet joint violation (FJV) is a potential risk factor for adjacent segment disease following lumbar fusion surgery. We sought to conduct a systematic review and meta-analysis to compare screw-related superior FJV rates between the open and different minimally invasive (MI) techniques-fluoroscopy-based, 3D-image navigation, and navigation with robotic assistance-in adult lumbar fusion surgery. METHODS: We searched original articles comparing the rates of screw-related FJV between the open and different MI techniques in adult lumbar fusion surgery for lumbar degenerative diseases in PubMed, EMBASE, and the Cochrane Library from inception to September 2021. We compared the numbers of top-level pedicle screws and associated superior FJVs in the main analyses and performed subgroup analysis based on different MI techniques to examine whether individual MI approaches differed in superior FJV rate. Risk ratio (RR) and 95% confidence interval (CI) were calculated in a random-effect meta-analysis. RESULTS: Included in the meta-analysis were 16 articles with 2655 patients and 4638 top-level pedicle screws. The pooled analysis showed no significant difference in superior FJV rates between the MI and open groups (RR: 0.89, 95% CI: 0.62-1.28). The subgroup analysis demonstrated that the overall rates of superior FJV were 27.1% (411/1518) for fluoroscopy-based, 7.1% (43/603) for 3D-image navigation, and 3.2% (7/216) for navigation with robotic assistance. Compared with the open method, the overall RRs were 1.53 (95% CI: 1.19-1.96) for fluoroscopy-based, 0.41 (95% CI: 0.22-0.75) for 3D-image navigation, and 0.25 (95% CI: 0.08-0.72) for navigation with robotic assistance. CONCLUSION: Among the three common MI techniques, fluoroscopy-based can be associated with a higher risk of superior FJV, while both 3D-image navigation and navigation with robotic assistance may be associated with lower risks as compared with the open method. Considering the limitations of the study, more trials are needed to prove these clinical findings.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Articulação Zigapofisária , Adulto , Humanos , Articulação Zigapofisária/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Fatores de Risco
15.
Epilepsia Open ; 8(1): 154-164, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36524291

RESUMO

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.


Assuntos
Polimicrogiria , Masculino , Feminino , Humanos , Lactente , Pré-Escolar , Criança , Adulto Jovem , Adulto , Irmãos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Mutação de Sentido Incorreto
16.
Nat Commun ; 13(1): 6385, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302784

RESUMO

Neutrophils play essential anti-microbial and inflammatory roles in host defense, however, their activities require tight regulation as dysfunction often leads to detrimental inflammatory and autoimmune diseases. Here we show that the adhesion molecule GPR97 allosterically activates CD177-associated membrane proteinase 3 (mPR3), and in conjugation with several protein interaction partners leads to neutrophil activation in humans. Crystallographic and deletion analysis of the GPR97 extracellular region identified two independent mPR3-binding domains. Mechanistically, the efficient binding and activation of mPR3 by GPR97 requires the macromolecular CD177/GPR97/PAR2/CD16b complex and induces the activation of PAR2, a G protein-coupled receptor known for its function in inflammation. Triggering PAR2 by the upstream complex leads to strong inflammatory activation, prompting anti-microbial activities and endothelial dysfunction. The role of the complex in pathologic inflammation is underscored by the finding that both GPR97 and mPR3 are upregulated on the surface of disease-associated neutrophils. In summary, we identify a PAR2 activation mechanism that directs neutrophil activation, and thus inflammation. The PR3/CD177/GPR97/PAR2/CD16b protein complex, therefore, represents a potential therapeutic target for neutrophil-mediated inflammatory diseases.


Assuntos
Ativação de Neutrófilo , Neutrófilos , Receptor PAR-2 , Receptores Acoplados a Proteínas G , Humanos , Inflamação/patologia , Mieloblastina/metabolismo , Ativação de Neutrófilo/fisiologia , Fagocitose , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
17.
BMC Musculoskelet Disord ; 23(1): 853, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088338

RESUMO

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.


Assuntos
Substitutos Ósseos , Vancomicina , Substitutos Ósseos/uso terapêutico , Humanos , Pós , Estudos Prospectivos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Vancomicina/efeitos adversos
18.
J Clin Med ; 11(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35807031

RESUMO

Gouty arthritis is the most common form of inflammatory arthritis and flares frequently after surgeries. Such flares impede early patient mobilization and lengthen hospital stays; however, little has been reported on gout flares after spinal procedures. This study reviewed a database of 6439 adult patients who underwent thoracolumbar spine surgery between January 2009 and June 2021, and 128 patients who had a history of gouty arthritis were included. Baseline characteristics and operative details were compared between the flare-up and no-flare groups. Multivariate logistic regression was used to analyze predictors and construct a predictive model of postoperative flares. This model was validated using a receiver operating characteristic (ROC) curve analysis. Fifty-six patients (43.8%) had postsurgical gout flares. Multivariate analysis identified gout medication use (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14−0.75; p = 0.009), smoking (OR, 3.23; 95% CI, 1.34−7.80; p = 0.009), preoperative hemoglobin level (OR, 0.68; 95% CI, 0.53−0.87; p = 0.002), and hemoglobin drop (OR, 1.93; 95% CI, 1.25−2.96; p = 0.003) as predictors for postsurgical flare. The area under the ROC curve was 0.801 (95% CI, 0.717−0.877; p < 0.001). The optimal cut-off point of probability greater than 0.453 predicted gout flare with a sensitivity of 76.8% and specificity of 73.2%. The prediction model may help identify patients at an increased risk of gout flare.

19.
Pharmaceuticals (Basel) ; 15(2)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35215331

RESUMO

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.

20.
J Chin Med Assoc ; 85(1): 129-135, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35006129

RESUMO

BACKGROUND: Restoration of height or angle has been reported following vertebroplasty (VP). The purpose of the study was to investigate the predictive value of the preoperative lateral fulcrum radiograph (LFR) of success in one-level VP for painful osteoporotic vertebral fracture. METHODS: From January 2017 to January 2018, 71 patients (mean age, 76 years) receiving VP were retrospectively analyzed. Painful vertebra was defined as pseudarthrosis or edematous change in magnetic resonance imaging (MRI) scan. Fulcrum flexibility (FF) and fulcrum restoration index (FRI) of the vertebral wedge angle (VWA), regional kyphotic angle (RKA), and anterior vertebral body height (AVBH) were investigated. Back pain was evaluated using a visual analogue scale. RESULTS: The 30 males and 41 females were followed for an average of 21 months. The sensitivity of LFR and MRI to detect pseudarthrosis was 92% and 97%, respectively. Preoperative FF of VWA, RKA, and AVBH was 52.4%, 58.3%, and 60%, respectively, indicating similar potential restoration ability. Postoperative average FRI for VWA, RKA, and AVBH was 1.29 ± 2.98, 0.46 ± 1.16, and 1.04 ± 1.68, respectively. Final average FRI was 0.94 ± 2.96, -0.03 ± 2.25, and 0.6 ± 2.04, respectively. VWA and AVBH had better immediate restoration, and VWA had better final maintenance. All parameters progressive lost significant levels of restoration to similar degrees but without increase in back pain. CONCLUSION: LFR can help with evaluation for pseudarthrosis and the restoration effect of VP. VP had better immediate restoration of VWA and AVBH and better final VWA maintenance.


Assuntos
Manejo da Dor , Radiografia/métodos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/fisiopatologia , Resultado do Tratamento
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