RESUMEN
Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.
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Proteínas Portadoras , Polaridad Celular , Proteínas de la Membrana , Columna Vertebral , Pez Cebra , Animales , Pez Cebra/genética , Pez Cebra/embriología , Humanos , Ratones , Polaridad Celular/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Columna Vertebral/anomalías , Columna Vertebral/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Escoliosis/genética , Escoliosis/congénito , Escoliosis/metabolismo , Vía de Señalización Wnt/genética , Predisposición Genética a la Enfermedad , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , FemeninoRESUMEN
Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system, respectively, due to defects in somitogenesis and neurulation. Somitogenesis and neurulation rely on factors secreted from neighbouring tissues and the integrity of the axial structure. Crucial signalling pathways like Wnt, Notch and planar cell polarity regulate somitogenesis and neurulation with significant crosstalk. While previous studies suggest an association between CVMs and NTDs, the exact mechanism underlying this relationship remains unclear. In this review, we explore embryonic development, signalling pathways and clinical phenotypes involved in the association between CVMs and NTDs. Moreover, we provide a summary of syndromes that exhibit occurrences of both CVMs and NTDs. We aim to provide insights into the potential mechanisms underlying the association between CVMs and NTDs, thereby facilitating clinical diagnosis and management of these anomalies.
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Defectos del Tubo Neural , Femenino , Embarazo , Humanos , Defectos del Tubo Neural/epidemiología , Defectos del Tubo Neural/genética , Columna Vertebral/metabolismo , Desarrollo Embrionario , Neurulación/genética , Transducción de Señal/genéticaRESUMEN
OBJECTIVES: To assess the impact of diabetes mellitus (DM) on the postoperative motor and somatosensory functional recoveries of degenerative cervical myelopathy (DCM) patients. METHODS: Motor and somatosensory evoked potentials (MEP and SSEPs) and modified Japanese Orthopedic Association (mJOA) scores were recorded in 27 diabetic (DCM-DM group) and 38 non-diabetic DCM patients (DCM group) before and 1 year after surgery. The central motor (CMCT) and somatosensory (CSCT) conduction time were recorded to evaluate the conductive functions of the spinal cord. RESULTS: The mJOA scores, CMCT and CSCT improved (t test, p < 0.05) in both of the DCM-DM and DCM groups 1 year after surgery. The mJOA recovery rate (RR) and CSCT recovery ratio were significantly worse (t test, p < 0.05) in the DCM-DM group compared to the DCM group. DM proved to be a significant independent risk factor for poor CSCT recovery (OR = 4.52, 95% CI 2.32-7.12) after adjusting for possible confounding factors. In DCM-DM group, CSCT recovery ratio was also correlated with preoperative HbA1 level (R = - 0.55, p = 0.003). Furthermore, DM duration longer than 10 years and insulin dependence were risk factors for lower mJOA, CMCT and CSCT recoveries among all DCM-DM patients (t test, p < 0.05). CONCLUSIONS: DM may directly hinders spinal cord conduction recovery in DCM patients after surgery. Corticospinal tract impairments are similar between DCM and DCM-DM patients, but significantly worsened in chronic or insulin-dependent DM patients. The dorsal column is more sensitively affected in all DCM-DM patients. Deeper investigation into the mechanisms and neural regeneration strategies is needed.
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Diabetes Mellitus , Insulinas , Enfermedades de la Médula Espinal , Humanos , Vértebras Cervicales/cirugía , Enfermedades de la Médula Espinal/cirugía , Diabetes Mellitus/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.
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Predisposición Genética a la Enfermedad , Escoliosis/diagnóstico , Escoliosis/genética , Adolescente , Adulto , Edad de Inicio , Preescolar , China/epidemiología , Estudios de Cohortes , Exoma/genética , Femenino , Humanos , Masculino , Estudios Retrospectivos , Escoliosis/clasificación , Escoliosis/patología , Secuenciación del ExomaRESUMEN
BACKGROUND: To compare the safety and efficacy of tranexamic acid (TXA)-soaked absorbable Gelfoam and the retrograde injection of TXA through a drain with drain-clamping in degenerative cervical laminoplasty patients. METHODS: Patients were assigned into either TXA retrograde injection (TXA-RI), TXA-soaked absorbable Gelfoam (TXA-Gel), or control groups. The demographics, operative measurements, volume and length of drainage, length of hospital stay, complete blood cell count, coagulopathy, postoperative complications, and blood transfusion were recorded. RESULTS: We enrolled 133 patients, with 44, 44, and 45 in the TXA-RI, TXA-Gel, and control groups, respectively. The baseline characteristics did not differ significantly among the three groups. The TXA-RI group exhibited a lower volume and length of postoperative drainage compared to the TXA-Gel and control groups (126.60 ± 31.27 vs. 156.60 ± 38.63 and 275.45 ± 75.27 mL; 49.45 ± 9.70 vs 58.70 ± 10.46 and 89.31 ± 8.50 hours, all P < 0.01). The TXA-RI group also had significantly shorter hospital stays compared to the control group (5.31 ± 1.18 vs 7.50 ± 1.25 days, P < 0.05) and higher hemoglobin and hematocrit levels (12.58 ± 1.67 vs 11.28 ± 1.76 g/dL; 36.62 ± 3.66% vs 33.82 ± 3.57%, both P < 0.05) at hospital discharge. In the TXA-RI and TXA-Gel groups, the D-dimmer (DD) and fibrinogen (FIB) were significantly lower than those in the control group after surgery (P < 0.05). None of the patients required blood transfusion. No complications, including thromboembolic events, were reported. CONCLUSION: Topical retrograde injection of TXA through a drain with drain-clamping at the conclusion of unilateral posterior cervical expansive open-door laminoplasty may effectively reduce postoperative blood loss and the length of hospital stays without increasing postoperative complications.
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Antifibrinolíticos , Laminoplastia , Ácido Tranexámico , Antifibrinolíticos/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Catéteres , Constricción , Drenaje , Esponja de Gelatina Absorbible/efectos adversos , Humanos , Laminoplastia/efectos adversos , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Ácido Tranexámico/efectos adversosRESUMEN
BACKGROUND: Diagnosing chronic periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the serum neutrophil-to-lymphocyte ratio (NLR) in aiding the diagnosis of chronic PJI. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 158 patients who had undergone revision arthroplasty (104 with aseptic mechanic failure and 54 with chronic PJI) from July 2011 to July 2020. Univariate analysis followed by multivariate logistic regression was applied to compare NLR, C-reactive protein (CRP), and erythrocyte sedimentation ratio (ESR) between the two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with CRP and ESR. RESULTS: NLR, CRP, and ESR were significantly higher in patients with chronic PJI than in the aseptic revision group (p < 0.05). ROC curve analysis revealed that NLR had a sensitivity of 57.41% and a specificity of 77.88% with an optimal threshold of 2.56. The optimal threshold for CRP and ESR was 7.00 mg/L (sensitivity 62.50% and specificity 83.12%) and 43 mm/h (sensitivity 59.38% and specificity 80.52%), respectively. The combined diagnostic value of NLR with CRP and ESR was shown to have no additional diagnostic value in predicting chronic PJI. CONCLUSION: Compared with traditional inflammatory biomarkers (ESR and CRP), the value of serum NLR alone or combined with CRP and ESR for diagnosing chronic PJI is limited. LEVEL OF EVIDENCE: Level 3.
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Artroplastia de Reemplazo de Cadera , Infecciones Relacionadas con Prótesis , Biomarcadores , Humanos , Linfocitos , Neutrófilos , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/cirugía , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Congenital scoliosis (CS) is a birth defect with variable clinical and anatomical manifestations due to spinal malformation. The genetic etiology underlying about 10% of CS cases in the Chinese population is compound inheritance by which the gene dosage is reduced below that of haploinsufficiency. In this genetic model, the trait manifests as a result of the combined effect of a rare variant and common pathogenic variant allele at a locus. From exome sequencing (ES) data of 523 patients in Asia and two patients in Texas, we identified six TBX6 gene-disruptive variants from 11 unrelated CS patients via ES and in vitro functional testing. The in trans mild hypomorphic allele was identified in 10 of the 11 subjects; as anticipated these 10 shared a similar spinal deformity of hemivertebrae. The remaining case has a homozygous variant in TBX6 (c.418C>T) and presents a more severe spinal deformity phenotype. We found decreased transcriptional activity and abnormal cellular localization as the molecular mechanisms for TBX6 missense loss-of-function alleles. Expanding the mutational spectrum of TBX6 pathogenic alleles enabled an increased molecular diagnostic detection rate, provided further evidence for the gene dosage-dependent genetic model underlying CS, and refined clinical classification.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Patrón de Herencia , Mutación Missense , Proteínas de Dominio T Box/genética , Alelos , Línea Celular , Femenino , Expresión Génica , Genes Reporteros , Genotipo , Haplotipos , Humanos , Masculino , Modelos Moleculares , Técnicas de Diagnóstico Molecular , Fenotipo , Conformación Proteica , Radiografía , Análisis de Secuencia de ADN , Columna Vertebral/anomalías , Columna Vertebral/diagnóstico por imagen , Relación Estructura-Actividad , Proteínas de Dominio T Box/química , Secuenciación del ExomaRESUMEN
Congenital scoliosis (CS) is a form of scoliosis caused by congenital vertebral malformations. Genetic predisposition has been demonstrated in CS. We previously reported that TBX6 loss-of-function causes CS in a compound heterozygous model; however, this model can explain only 10% of CS. Many monogenic and polygenic CS genes remain to be elucidated. In this study, we analyzed exome sequencing (ES) data of 615 Chinese CS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) project. Cosegregation studies for 103 familial CS identified a novel heterozygous nonsense variant, c.2649G>A (p.Trp883Ter) in FBN1. The association between FBN1 and CS was then analyzed by extracting FBN1 variants from ES data of 574 sporadic CS and 828 controls; 30 novel variants were identified and prioritized for further analyses. A mutational burden test showed that the deleterious FBN1 variants were significantly enriched in CS subjects (OR = 3.9, P = 0.03 by Fisher's exact test). One missense variant, c.2613A>C (p.Leu871Phe) was recurrent in two unrelated CS subjects, and in vitro functional experiments for the variant suggest that FBN1 may contribute to CS by upregulating the transforming growth factor beta (TGF-ß) signaling. Our study expanded the phenotypic spectrum of FBN1, and provided nove insights into the genetic etiology of CS.
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Anomalías Congénitas/genética , Fibrilina-1/genética , Predisposición Genética a la Enfermedad , Escoliosis/genética , Niño , Preescolar , Codón sin Sentido/genética , Anomalías Congénitas/diagnóstico por imagen , Anomalías Congénitas/fisiopatología , Exoma/genética , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Masculino , Mutación , Mutación Missense/genética , Linaje , Escoliosis/diagnóstico por imagen , Escoliosis/fisiopatología , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/fisiopatología , Factor de Crecimiento Transformador beta/genéticaRESUMEN
STUDY DESIGN: Diagnostic accuracy study with prospectively collected data. OBJECTIVE: This study aimed to establish optimal cutoff values for the 10-second grip and release (10s-G&R) Test to distinguish between mild, moderate, and severe levels of hand dexterity impairment in patients with degenerative cervical myelopathy (DCM). BACKGROUND: The 10s-G&R test is widely utilized to assess hand function in DCM patients. However, whether this test can effectively distinguish between varying severities of hand dexterity impairment, along with the relevant cutoff values, remains unknown. MATERIALS AND METHODS: The authors analyzed hand motion data from 551 consecutively enrolled DCM patients using an artificial intelligent system. In addition, the authors conducted evaluations of functional status, quality of life, and outcome measures. Receiver operating curve analysis was performed to determine cutoff values that differentiate mild, moderate, and severe hand dexterity impairments based on the ability to fasten buttons, as assessed by the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire Q2-1. The validity of these cutoffs was assessed by comparing G&R parameters, upper limb disability, overall disease severity, and quality of life among patients in different severity groups. RESULTS: The authors identified 16 G&R cycles as the cutoff for moderate hand dexterity impairment and 13 G&R cycles as the cutoff for severe impairment. Patients with severe impairment exhibited significantly worse G&R parameters, more severe upper limb symptoms, greater overall disease severity, and reduced quality of life. Patients completing fewer than 13 G&R cycles within 10 seconds were more likely to have moderate-to-severe DCM, indicating the need for potential surgical intervention. CONCLUSION: The authors propose classifying mild hand dexterity impairment as 17 to 20 cycles on the 10s-G&R test, moderate as 14 to 16 cycles, and severe as 13 cycles or less. Our study underscores that the 10s-G&R test can serve as an effective supplementary tool within the context of other currently available measurement tools.
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Calidad de Vida , Enfermedades de la Médula Espinal , Humanos , Vértebras Cervicales/cirugía , Enfermedades de la Médula Espinal/cirugía , Extremidad Superior , Fuerza de la ManoRESUMEN
Objective: The mechanisms of intervertebral disc degeneration (IVDD) in low back pain (LBP) patients are multiples. In this study, we attempt to investigate whether melatonergic system plays a potential role in IVDD patients with LBP by analyzing their clinical specimens. The fucus will be given to the correlation between the melatonin receptor expression and intervertebral disc tissue apoptosis. Methods: In this clinical study, 107 lumbar intervertebral disc nucleus pulposus (NP) specimens from patients with LBP were collected with patients' consents. The disc height (DH) discrepancy ratio, range of motion and sagittal parameters of the pathological plane were measured and Pfirrmann grade was used to classified the grades of IVDD level. Discs at grades 1-3 were served as normal control and grades 4-5 were considered as IVDD. The expression levels of melatonin receptor 1A (MT1) and 1B (MT2) were measured by immunohistochemistry. The apoptosis of NP was assessed using TUNEL staining. Their potential associations among MT1/2, DH, apoptosis, sagittal parameters with IVDD and LBP were evaluated with statistical analysis. Results: The incidence of IVDD was positively associated with age and negatively related to VAS scores for LBP (p < 0.001). Patients with higher degree of IVDD also have higher DH discrepancy ratio (p < 0.001), higher prevalence of lumbar instability (p = 0.003) and higher cell apoptosis compared to the control. Nevertheless, no statistically significant correlation was identified between Pfirrmann grade and lumbar sagittal parameters. MT1 and MT2 both were highly expressed in the NP tissues. Importantly, MT1 expression but not MT2 was significantly increased in the intervertebral disc tissue of patients with IVDD and its level correlated well with cell apoptosis level and the severity of IVDD as well as lower VAS scores for LBP. Conclusion: The highly elevated MT1 expression was found in NP tissues of patients with IVDD and LBP compared to the control. This phenomenon probably reflects the compensating response of the body to the pathological alteration of the IVDD and LBP. Therefore, these findings provide the novel information to use selective agonists of MT1 to target IVDD and LBP clinically.
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Apoptosis , Degeneración del Disco Intervertebral , Dolor de la Región Lumbar , Humanos , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Dolor de la Región Lumbar/patología , Dolor de la Región Lumbar/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Vértebras Lumbares/patología , Receptor de Melatonina MT1/metabolismo , Receptor de Melatonina MT2/metabolismo , Anciano , Disco Intervertebral/patología , Disco Intervertebral/metabolismoRESUMEN
OBJECTIVE: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. METHODS: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. RESULTS: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. CONCLUSION: DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.
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BACKGROUND: Despite advancements in school scoliosis screening (SSS), there are still no effective indicators to estimate the severity of spinal curvature. We aim to investigate the association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis (AIS) among Chinese adolescents. METHODS: In this SSS program, we examined the incorrect posture, Adam's forward bending test (FBT) results, and angle of trunk rotation (ATR) in adolescents. Those with suspected scoliosis were referred for a standing anteroposterior whole-spine radiography as outpatients. The radiographic data of 426 students with lateral Cobb angles were collected from 2016 to 2022 and the associations were studied using logistic regression (LR) models and receiver operating characteristic (ROC) curves. RESULTS: Univariate LR revealed that female gender [odds ratio (OR) = 2.92, 95% confidence interval (CI) 1.67-5.09, P < 0.001], age 16-19y (OR = 2.83, 95%CI 1.10-7.28, P = 0.031), right shoulder height (OR = 2.15, 95%CI 1.23-3.75, P = 0.007), right scapula tilt (OR = 2.03, 95%CI 1.18-3.50, P = 0.010), right rib hump (OR = 1.88, 95%CI 1.23-2.85, P = 0.003), right thoracic rotation ≥ 5° (OR = 2.14, 95%CI 1.43-3.20, P < 0.001), and left thoracolumbar kyphosis (OR = 3.79, 95%CI 1.06-13.56, P = 0.041) were all significantly associated with the severity of the curve magnitude. Multivariate LR showed that female gender [adjusted OR (AOR) = 3.23, 95%CI 1.81-5.73, P < 0.001], those aged 16-19y (AOR = 5.08, 95%CI 1.86-13.91, P = 0.002), and with a right rib hump (AOR = 1.72, 95%CI 1.11-2.64, P = 0.015) presented with a higher risk of severe curve magnitude than men, those aged 7-12y, and without a rib hump, respectively. ROC curves further proved that sex, age, shoulder-height difference, scapula tilt, flat back, rib hump, angle of thoracic rotation were the risk predictors for curve magnitude. CONCLUSION: Incorrect posture and ATR, especially the right rib hump, were significantly associated with the curve magnitude of AIS. Early screening for incorrect postures and ATR could be an effective and economical strategy to predict the severity of AIS through SSS in Chinese adolescents.
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Postura , Escoliosis , Humanos , Escoliosis/diagnóstico por imagen , Escoliosis/fisiopatología , Adolescente , Femenino , Masculino , China/epidemiología , Postura/fisiología , Adulto Joven , Índice de Severidad de la Enfermedad , RadiografíaRESUMEN
OBJECTIVE: Irrigation is a conventional treatment for acute and chronic periprosthetic joint infections (PJI). However, there has been no unified standard for irrigation during surgery for PJI in the past, and the efficacy is uncertain. The purpose of this study is to create a new irrigation protocol to enhance the infection control rate and reduce the postoperative recurrence rate of PJI patients. METHODS: We conducted a single-institution retrospective review with a total of 56 patients who underwent revision total hip or knee arthroplasties due to PJI from January 2011 to January 2022. Conventional irrigation (CI) was used in 32 cases, and standard operating procedure of irrigation (SOPI) was used in 24. The CI protocol carries out an empirical irrigation after debridement, which is quite random. Our SOPI protocol clearly stipulates the soaking concentration and time of hydrogen peroxide and povidone-iodine. The irrigation is carried out three times, and tissue samples are taken from multiple parts before and after irrigation, which are sent for microbial culture. The important statistical indicators were the rate of positive microbiological culture and postoperative recurrence rate with an average follow-up of 24 average months. RESULTS: The drainage volume was lower in the SOPI group than in the CI group on postoperative day 3 (p < 0.01) and 7 (p = 0.016). In addition, the percentage of positive microbiological cultures after the third irrigation was less than that before (p < 0.01) and after (p < 0.01) the first irrigation. The most common causative organism was Staphylococcus aureus, which was detected in 25.0% and 12.5% of the SOPI and CI groups, respectively. The failure rate at the final follow-up was 8.3% and 31.3% (p = 0.039) for the SOPI and CI groups, respectively. CONCLUSION: Compared with the traditional CI method, SOPI standardized the soaking time of hydrogen peroxide and povidone-iodine, increased the frequency of and irrigation, and proved that microorganisms were almost completely removed through the microbial culture of multiple tissues. SOPI has the potential to become a standardized irrigation process worthy of promotion, effectively reducing the postoperative recurrence rate of PJI patients.
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Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Humanos , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Relacionadas con Prótesis/etiología , Resultado del Tratamiento , Povidona Yodada/uso terapéutico , Peróxido de Hidrógeno , Artroplastia de Reemplazo de Rodilla/efectos adversosRESUMEN
STUDY DESIGN: A prospective cohort study. OBJECTIVES: To report a new index, the realigned K-line, for predicting surgical outcomes after laminoplasty in patients with degenerative cervical myelopathy (DCM). METHODS: One hundred twenty-eight patients with DCM undergoing laminoplasty were enrolled from January 2018 to April 2021 in our department. A realigned K-line was defined as the line connecting the midpoints of the spinal cord between C2 and C7 on realigned T1-weighted magnetic resonance imaging. The minimum interval between the anterior compression factors of the spinal cord and the realigned K-line (INTrea), and the modified K-line (INTmod) were measured. A logistic regression analysis was performed to identify factors associated with unsatisfactory surgical outcomes. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was applied to evaluate the reliability of the multivariate logistic regression model. RESULTS: Univariate analysis showed that the score for the bladder function section of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire, numeric rating scale scores for arm pain, and INTrea might be related to the Japanese Orthopaedic Association (JOA) recovery rate (RR) not achieving the minimal clinically important difference (MCID) (P < .05). Only INTrea (odds ratio = .744, P < .05) was an independent preoperative factor related to the JOA RR not achieving the MCID (area under the curve, .743). A cutoff of 5.0 mm for INTrea had an accuracy of 71.9% and specificity of 80.3% for predicting the JOA RR not achieving the MCID. CONCLUSIONS: INTrea is an independent preoperative risk factor related to the JOA RR not achieving the MCID in patients with DCM. A cutoff point of 5.0 mm is most appropriate for alerting spine surgeons to a high likelihood of the JOA RR not achieving the MCID.
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Pathogenic variants in MYH3 cause distal arthrogryposis type 2A and type 2B3 as well as contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B. These disorders are ultra-rare and their natural course and phenotypic variability are not well described. In this study, we summarize the clinical features and genetic findings of 17 patients from 10 unrelated families with vertebral malformations caused by dominant or recessive pathogenic variants in MYH3. Twelve novel pathogenic variants in MYH3 (NM_002470.4) were identified: three of them were de novo or inherited in autosomal dominant way and nine were inherited in autosomal recessive way. The patients had vertebral segmentation anomalies accompanied with variable joint contractures, short stature and dysmorphic facial features. There was a significant phenotypic overlap between dominant and recessive MYH3-associated conditions regarding the degree of short stature as well as the number of vertebral fusions. All monoallelic variants caused significantly decreased SMAD3 phosphorylation, which is consistent with the previously proposed pathogenic mechanism of impaired canonical TGF-ß signaling. Most of the biallelic variants were predicted to be protein-truncating, while one missense variant c.4244T>G,p.(Leu1415Arg), which was inherited in an autosomal recessive way, was found to alter the phosphorylation level of p38, suggesting an inhibition of the non-canonical pathway of TGF-ß signaling. In conclusion, the identification of 12 novel pathogenic variants and overlapping phenotypes in 17 affected individuals from 10 unrelated families expands the mutation and phenotype spectrum of MYH3-associated skeletal disorders. We show that disturbances of canonical or non-canonical TGF-ß signaling pathways are involved in pathogenesis of MYH3-associated skeletal fusion (MASF) syndrome.
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Aseptic loosening caused by peri-implant osteolysis (PIO) is a common complication after joint replacement, and there is still no better treatment than revision surgery. The wear particle-induced inflammation response, especially subsequent osteoclastic bone resorption, is responsible for PIO. As the importance of wear particles in inducing autophagy in cells around the prosthesis in PIO has been discovered, this might be a central process underlying aseptic loosening. However, the role of autophagy induced by wear particles in osteoclastogenesis during PIO remains unclear. In this study, we investigated the role of autophagy in osteoclastogenesis and verified it in a mouse calvarial osteolysis model. We found that osteoclasts were increased in the interface membranes of patients with aseptic loosening. In vitro, knocking down the Atg5 gene or using autophagy inhibitors (3-MA, LY294002) to inhibit autophagy was found to repress osteoclastogenesis and decrease expression of the osteoclast-related genes TRAP, cathepsin K, and matrix metalloprotein 9 (MMP-9) with or without titanium (Ti) particles. In vivo, 3-MA and LY294002 repressed Ti particle-stimulated osteolysis and osteoclastogenesis and reduced expression of the pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Our results suggest that 3-MA and LY294002 might be the potential medicines to prevent and treat PIO and aseptic loosening.
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Osteólisis , Animales , Autofagia , Cromonas , Humanos , Ratones , Ratones Endogámicos C57BL , Morfolinas , Osteoclastos , Osteogénesis , Osteólisis/inducido químicamente , Titanio/efectos adversosRESUMEN
OBJECTIVES: To investigate abnormally methylated-differentially expressed genes (DEGs) and their related pathways in osteoarthritis (OA) by comprehensive bioinformatic analysis. METHODS: Gene expression profiles of GSE51588 and GSE114007, and a gene methylation microarray data GSE63695 were downloaded from the Gene Expression Omnibus (GEO) repository. Abnormally methylated DEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of these genes were subsequently performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction (PPI) network was built from STRING. Module analysis and hub gene identification were performed by using Cytoscape. Co-expression analysis was also constructed using the CEMiTool package. RESULTS: In total, 133 abnormally methylated DEGs were identified, including 85 hypomethylation high-expression genes and 48 hypermethylation low-expression genes. Among biological processes and KEGG pathways of abnormally methylated DEGs, collagen fibril organization was enriched most frequently, and pathways of oxidative stress and aging were enriched, including HIF-1 signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. In PPI networks, the hub genes of hypomethylation high-expression genes were COL1A1, COL3A1, COL1A2, COL5A2, LUM, MMP2, SPARC, COL2A1, COL6A2, and COL7A1, and the hub genes of hypermethylation low-expression genes were VEGFA, SLC2A1, LDHA, PDK1, and BNIP3. Combined with co-expression analysis, COL3A1, LUM, and MMP2 were the critical hypomethylation high-expression hub genes in medial tibia subchondral bone. CONCLUSIONS: Our study implied abnormally methylated DEGs and dysregulated pathways in OA. Common methylation biomarkers included COL3A1, LUM, and MMP2, and we also found that THBS2 may serve as a novel biomarker in end-stage OA. Key Points ⢠Abnormally methylated differentially expressed genes regulate osteoarthritis. ⢠Hypomethylation high-expression genes were related to the extracellular matrix. ⢠Hypermethylation low-expression genes were related to oxidative stress and aging. ⢠COL3A1, LUM, and MMP2 were potential methylation biomarkers for osteoarthritis.
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Biología Computacional , Osteoartritis , Metilación de ADN , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Osteoartritis/genéticaRESUMEN
Background: Inflammatory osteolysis induced by wear particles is the major cause of prosthetic loosening after artificial joint replacement, and its prevention and treatment are difficult worldwide. Our previous study confirmed that sphingosine kinases (SPHKs) are important mediators regulating the wear particle-induced macrophage inflammatory response. However, it is unclear whether SPHKs can modulate chronic inflammation and alleviate osteolysis. Zoledronic acid (ZA), an imidazole-containing bisphosphonate, directly affects osteoclasts and prevents bone mineral-related diseases. However, the effects of SPHK inhibitors and ZA used to treat periprosthetic osteolysis are unknown. Methods: We applied tartrate-resistant acid phosphatase (TRAP) staining to evaluate bone destruction in the interface membranes of patients with aseptic loosening and a control group. A murine calvarial osteolysis model was used to examine the preventative effect of SPHK inhibitors and ZA on osteolysis. Micro-CT scanning, immunohistochemistry (IHC), and histomorphometric analysis were conducted to determine the variations in inflammatory osteolysis. The effects of different drug concentrations on cell viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to confirm the reduced expression of osteoclast-specific genes after drug and titanium treatment. The osteoclast formation and functions of the drugs were analyzed using TRAP staining in vivo and in vitro. The effect of SPHKs/S1P-TRAF2-BECN1 signaling pathways was verified via RT-qPCR and tissue IHC. Results: In this study, we found that SPHK inhibitors (ABC294640 and FTY720) combined with ZA decreased the degree of inflammatory osteolysis in vivo. However, ABC294640 and ZA suppressed osteoclast differentiation and osteoclast-specific genes in vitro. SPHKs regulate the inflammatory osteolysis induced by wear particles by increasing the expression of SPHKs/S1P-TRAF2-BECN1. Conclusion: Our study revealed that wear particles could induce inflammatory osteolysis by upregulating SPHKs/S1P-TRAF2-BECN1 and SPHK inhibitors/ZA inhibit osteoclastogenesis in vitro and prevent inflammatory osteolysis in vivo, suggesting that SPHK inhibitors and ZA can be a new perspective and scientific basis for the prevention and treatment of prosthesis loosening.
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BACKGROUND: Perioperative hyperglycemia is a risk factor for postoperative complications after total joint arthroplasty (TJA). However, the variability of fasting blood glucose (FBG) after TJA remains unknown. We aimed to assess the fluctuation and extent of elevation of FBG following primary or revision TJA. METHODS: We retrospectively evaluated the medical records of 1788 patients who underwent primary or revision TJA between 2013 and 2018. We examined FBG values collected during 6 days of the perioperative period. The findings for each time point were evaluated with descriptive statistics. Postoperative glycemic variability was assessed by the coefficient of variation (CV). RESULTS: The final cohort included the medical records of 1480 patients (1417 primary and 63 revision). FBG was highest on postoperative day 1 in the primary and revision groups (P < 0.001), which had the highest number of hyperglycemic patients (FBG > 100 mg/dL), with 66.4% and 75.5% in the primary and revision groups, respectively. The CV of diabetics in the primary group, and diabetics and non-diabetics in the revision group, was higher than that of non-diabetics in the primary group. CONCLUSION: Postoperative day 1 showed the highest FBG levels and proportion of patients with hyperglycemia in the perioperative period. Primary group diabetics, and revision group diabetics and non-diabetics, had higher postoperative fluctuation of FBG than primary group non-diabetics. Frequent FBG monitoring may therefore be warranted in diabetic patients undergoing TJA, and all patients undergoing revision TJA.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Glucemia/metabolismo , Ayuno/sangre , Hiperglucemia/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Anciano , Biomarcadores/sangre , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Periodo Posoperatorio , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Periprosthetic joint infection (PJI) has been increasingly documented; however, its preoperative accurate diagnosis remains challenging. Furthermore, there is a dire need to identify appropriate and effective biomarkers. We aimed to evaluate the relationship between globulin, albumin to globulin (A/G) ratio, and development of PJI in patients undergoing revision total joint arthroplasty (TJA). METHODS: A retrospective study was conducted on patients who had undergone revision TJA between 2011 and 2018 (89 with aseptic mechanic failure and 38 with PJI). The serum proteins were explored using univariate analysis followed by multivariate logistic regression. The diagnostic performance of these proteins was assessed by the receiver operating characteristic (ROC) curve. RESULTS: Higher globulin levels (odds ratio [OR], 1.239; P < 0.001) and lower A/G ratio (OR, 0.007; P < 0.001) were strongly associated with the risk of PJI. ROC curve analysis demonstrated reasonable diagnostic performance for globulin (area under the curve [AUC], 0.77; sensitivity, 78.95%; and specificity, 69.66%) and A/G ratio (AUC, 0.779; sensitivity, 65.79%; and specificity, 78.65%). CONCLUSIONS: Both globulin and A/G ratio were associated with PJI and may serve as potential adjuvant biomarkers in the diagnosis of PJI.