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1.
J Robot Surg ; 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35788970

RESUMO

This study was performed to prospectively compare the clinical and radiographic outcomes between robot-assisted minimally invasive transforaminal lumbar interbody fusion (RA MIS-TLIF) and fluoroscopy-assisted minimally invasive transforaminal lumbar interbody fusion (FA MIS-TLIF) in patients with degenerative lumbar spinal diseases. One hundred and twenty-three patients with lumbar degenerative diseases (lumbar spinal stenosis with instability and spondylolisthesis [degenerative spondylolisthesis or isthmic spondylolisthesis]) who underwent MIS-TLIF in our hospital were included in this study. Sixty-one patients underwent RA MIS-TLIF (Group A) and 62 patients underwent FA MIS-TLIF (Group B). Group A was further divided into Subgroup AI (46 single-level procedures) and Subgroup AII (15 double-level procedures). Group B was further divided into Subgroup BI (45 single-level procedures) and Subgroup BII (17 double-level procedures). The clinical outcome parameters were the visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, operative time, number of intraoperative fluoroscopies, blood loss, postoperative hospital stay, and postoperative complications. The radiographic change measures were the accuracy of screw placement, facet joint violation (FJV), fusion status, and change in disc height at the proximal adjacent segment at the 2-year follow-up. There were no significant differences in the VAS and ODI scores, blood loss, or postoperative hospital stay between Groups A and B (p > 0.05). The operative time was longer in Group A than B (p = 0.018). The operative time was longer in Subgroup AI than BI (p = 0.001). However, there was no significant difference between Subgroups AII and BII (p > 0.05). There was no significant difference in the number of intraoperative fluoroscopies for patients between Groups A and B (p > 0.05). Although the number of intraoperative fluoroscopies for patients was significantly higher in Subgroup AI than BI (p = 0.019), there was no significant difference between Subgroups AII and BII (p > 0.05). The number of intraoperative fluoroscopies for the surgeon was significantly lower in Group A than B (p < 0.001). For surgeons, the difference in the average number of intraoperative fluoroscopies between Subgroups AI and AII was 2.98, but that between Subgroups BI and BII was 10.73. In Group A, three guide pins exhibited drift and one patient developed a lateral wall violation by a pedicle screw. One pedicle screw perforated the anterior wall of the vertebral body and another caused an inner wall violation in Group B. The rate of a perfect screw position (grade A) was higher in Group A than B (p < 0.001). However, there was no significant difference in the proportion of clinically acceptable screws (grades A and B) between the two groups. The mean FJV grade was significantly higher in Group B than A (p < 0.001). During at 2-year postoperative follow-up, there was no significant difference in the fusion status between the two groups (p > 0.05); however, the decrease in disc height at the proximal adjacent segment was significantly less in Group A than B (p < 0.001). Robot-assisted percutaneous pedicle screw placement is a safer and more accurate alternative to conventional freehand fluoroscopy-assisted percutaneous pedicle screw insertion in MIS-TLIF.

2.
Orthop Surg ; 14(7): 1527-1532, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35686521

RESUMO

BACKGROUND: Although it has been established that adolescent idiopathic cervical kyphosis (AICK) has no known cause, there are associated risk factors. However, the underlying causes remain puzzling. This case report presents severe AICK linked to chronic neck flexion postural habit, treated with combined anterior and posterior correction surgery and review of the literature. CASE PRESENTATION: A 16-year-old male with no history of trauma, surgery, or family history of spinal deformity complained of intolerable neck pain and rigidity. He developed an incessant reading of comic books at a very young age, and he preferred placing the book on the floor with his head flexed between his thighs. Acupuncture and massage therapy failed to relief symptoms. He had no neurological symptoms on examination and X-ray showed Cobb angle of 70.5°. MRI and CT scans showed no spinal cord compression or osteophyte formation. A combined anterior and posterior correction surgery was performed after a week of skull traction. The deformity was corrected, neck pain disappeared, and neck rotatory function maintained after posterior implant removal. The maximum follow-up was 10 years. CONCLUSIONS: The potential underlying risk factor observed in this case is unusual. Chronic neck flexion postural habit is a potential risk factor of severe AICK in some individuals.


Assuntos
Cifose , Fusão Vertebral , Adolescente , Vértebras Cervicais/cirurgia , Hábitos , Humanos , Cifose/complicações , Cifose/cirurgia , Masculino , Cervicalgia/etiologia , Leitura , Resultado do Tratamento
3.
Clin Spine Surg ; 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35675143

RESUMO

STUDY DESIGN: This was a retrospective case series. OBJECTIVE: The purpose of this study was to compare radiologic and clinical outcomes in patients with L4-L5 lumbar spinal stenosis (LSS) who had undergone either minimally invasive (MIS-) or open (O-) transforaminal lumbar interbody fusion (TLIF), especially with regard to the development of adjacent segment degeneration (ASDeg). SUMMARY OF BACKGROUND DATA: ASDeg is defined as the degenerative changes at adjacent segments of a fused segment, with no obvious clinical symptoms. MATERIALS AND METHODS: A total of 121 LSS patients with a minimum 5-year follow-up were included. Patients were divided into 2 groups according to the surgery performed (MIS-TLIF: 57 patients, O-TLIF: 64 patients). Preoperative and final follow-up radiologic parameters were determined. The incidence of ASDeg was evaluated and compared between the 2 groups. Visual Analog Scale score, Japanese Orthopaedic Association score, and Oswestry Disability Index were used to assess clinical outcomes. RESULTS: Before surgery, no significant difference was found between MIS-TLIF and O-TLIF groups regarding demographic, radiologic, and clinical data. After a 5-year follow-up, the incidence of ASDeg in LSS patients was 47.1% (57/121). ASDeg was mostly located at the cranial segment of the fused level in each group. The most common type of ASDeg in both groups was intervertebral space collapse. There was a lower chance of ASDeg in MIS-TLIF group than that in O-TLIF group (33.3% vs. 59.4%, P<0.01). Postoperatively, both groups had significant improvement in clinical outcomes, and there were no statistically significant intergroup differences assessed by Visual Analog Scale, Japanese Orthopaedic Association, and Oswestry Disability Index scores. CONCLUSION: The clinical effect of MIS-TLIF and O-TLIF were similar, but the incidence of ASDeg was significantly lower after MIS-TLIF at 5-year follow-up.

4.
Liver Int ; 42(5): 1097-1108, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35257483

RESUMO

BACKGROUND & AIMS: Genetic factors underlie a substantial proportion of paediatric liver diseases. Hereditary liver diseases have considerable genetic heterogeneity and variable clinical manifestations, which bring great challenges to clinical and molecular diagnoses. In this study, we investigated a group of paediatric patients with varying degrees of liver dysfunction using a hierarchical genetic testing strategy. METHODS: We first applied a panel encompassing 166 known causal genes of liver disease. We then used exome sequencing (ES) in those patients whose cases remained undiagnosed to identify the genetic aetiology of their symptoms. RESULTS: In total, we enrolled 131 unrelated paediatric patients with liver disease of Chinese Han ethnicity. We first applied targeted gene sequencing of 166 genes to all patients and yielded a diagnostic rate of 35.9% (47 of 131). Eighty-four patients who remained undiagnosed after target gene sequencing were subjected to ES. As a result, eight (8/84, 9.5%) of them obtained molecular diagnoses, including four patients suspected of abnormal bilirubin metabolism and four idiopathic cases. Non-typical genetic findings, including digenic inheritance and dual molecular diagnosis, were also identified. Through a comprehensive assessment of novel candidate variants of uncertain disease association, 11 patients of the remaining undiagnosed patients were able to obtain likely molecular diagnoses. CONCLUSIONS: Our study presents evidence for the diagnostic utility of sequential genetic testing in a cohort of patients with paediatric liver disease. Our findings expand the understanding of the phenotypic and mutational spectrum underlying this heterogeneous group of diseases.


Assuntos
Exoma , Hepatopatias , Criança , Testes Genéticos , Humanos , Hepatopatias/diagnóstico , Hepatopatias/genética , Mutação , Sequenciamento Completo do Exoma
5.
NPJ Genom Med ; 7(1): 11, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169139

RESUMO

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.

6.
Am J Hum Genet ; 109(2): 270-281, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35063063

RESUMO

In recent years, exome sequencing (ES) has shown great utility in the diagnoses of Mendelian disorders. However, after rigorous filtering, a typical ES analysis still involves the interpretation of hundreds of variants, which greatly hinders the rapid identification of causative genes. Since the interpretations of ES data require comprehensive clinical analyses, taking clinical expertise into consideration can speed the molecular diagnoses of Mendelian disorders. To leverage clinical expertise to prioritize candidate genes, we developed PhenoApt, a phenotype-driven gene prioritization tool that allows users to assign a customized weight to each phenotype, via a machine-learning algorithm. Using the ability to rank causative genes in top-10 lists as an evaluation metric, baseline analysis demonstrated that PhenoApt outperformed previous phenotype-driven gene prioritization tools by a relative increase of 22.7%-140.0% in three independent, real-world, multi-center cohorts (cohort 1, n = 185; cohort 2, n = 784; and cohort 3, n = 208). Additional trials showed that, by adding weights to clinical indications, which should be explained by the causative gene, PhenoApt performance was improved by a relative increase of 37.3% in cohort 2 (n = 471) and 21.4% in cohort 3 (n = 208). Moreover, PhenoApt could assign an intrinsic weight to each phenotype based on the likelihood of its being a Mendelian trait using term frequency-inverse document frequency techniques. When clinical indications were assigned with intrinsic weights, PhenoApt performance was improved by a relative increase of 23.7% in cohort 2 and 15.5% in cohort 3. For the integration of PhenoApt into clinical practice, we developed a user-friendly website and a command-line tool.


Assuntos
Doenças Genéticas Inatas/genética , Perda Auditiva Neurossensorial/genética , Deficiência Intelectual/genética , Aprendizado de Máquina , Microcefalia/genética , Nistagmo Congênito/genética , Escoliose/genética , Estudos de Coortes , Biologia Computacional , Bases de Dados Genéticas , Exoma , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/patologia , Testes Genéticos , Genótipo , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/patologia , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Microcefalia/diagnóstico , Microcefalia/patologia , Nistagmo Congênito/diagnóstico , Nistagmo Congênito/patologia , Fenótipo , Escoliose/diagnóstico , Escoliose/patologia , Software , Sequenciamento Completo do Exoma
7.
J Pain Res ; 15: 13-22, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023967

RESUMO

BACKGROUND: Sciatica-related spinal imbalance could be observed in lumbar disc herniation (LDH) patients. However, their characteristics and recovery process remained unclear. The purpose was to analyze the radiological characteristics of spinal imbalance related to sciatica and recovery following endoscopic discectomy. METHODS: The records of LDH patients with sciatica and spinal imbalance receiving endoscopic discectomy were retrospectively reviewed. The patients were divided to Group A (sagittal imbalance), Group B (coronal imbalance) and Group C (sagittal and coronal imbalance). The whole-spine x-ray was performed at pre-operation, immediately post-operation, 3-month and 6-month follow-up and related radiological parameters were measured. RESULTS: A total of 110 LDH patients (18.3%) presented with spinal imbalance were included and there were 31 patients in Group A, 38 patients in Group B and 41 patients in Group C. In this study, 77.2% of the coronal imbalance patients present with trunk shifted to contralateral side of disc herniation and 65.3% of the sagittal imbalance patients present with forward trunk. Most patients present mild and moderate sagittal and coronal imbalance. The magnitude of sagittal and coronal imbalance in Group C was significantly more severe than that of Group A and Group B. Most patients (≥75%) acquired spinal balance immediately after surgery. The sagittal imbalance improved better than coronal imbalance and single plane imbalance improved better than biplane imbalance. At the postoperative 6-month follow-up, all patients recovered to normal sagittal and coronal balance. CONCLUSION: Sciatica-related spinal imbalance occurs in 18.3% of the LDH patients receiving endoscopic discectomy. Different subgroups of spinal imbalance present different characteristics. Spontaneous correction of the spinal imbalance could be achieved when sciatica was relieved immediately after surgery and well maintained during follow-up.

8.
Pain Physician ; 25(1): E73-E86, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35051154

RESUMO

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and percutaneous endoscopic TLIF (PE-TILF) have been widely used in spine surgery. The use of a robot-guided technique provided several advantages; however, few studies have investigated the clinical outcomes of robot-assisted PE-TLIF (PE RA-TLIF). OBJECTIVE: The aim of this prospective cohort study was to compare the clinical outcomes of PE RA-TLIF with MIS-TLIF for the treatment of lumbar 4-5 (L4-5) spondylolisthesis. STUDY DESIGN: Prospective cohort study. SETTING: Qilu Hospital of Shandong University. METHODS: Fifty-eight cases diagnosed with L4-5 spinal stenosis with instability and Meyerding grade I spondylolisthesis (degenerative spondylolisthesis or isthmic spondylolisthesis) were included in this study. Twenty-six patients (group A) were treated with PE RA-TLIF, and the others (group B) underwent MIS-TLIF. The surgical procedures for PE RA-TLIF included the percutaneous implantation of pedicle screws (PS) under robot guidance, percutaneous fully endoscopic transforaminal decompression, and interbody fusion. The Japanese Orthopedic Association (JOA) score, the visual analog scale (VAS) for low back pain (LBP), the VAS for leg pain/numbness, and the Oswestry disability index (ODI) were used as follow-up clinical outcomes, and the lumbar interbody fusion rate was evaluated by CT. All statistical analyses were performed with SPSS 22.0, and the results were presented as mean ± standard deviation (SD). RESULTS: There were 4 cases of spinal stenosis with instability, 17 cases of degenerative spondylolisthesis, and 5 cases of isthmic spondylolisthesis in group A. For group B, there were 6 cases of spinal stenosis with instability, 19 cases of degenerative spondylolisthesis, and 7 cases of isthmic spondylolisthesis. The preoperative scores for the JOA, ODI, VAS for LBP, and VAS for leg pain were not statistically comparable between the 2 groups (P > 0.05). The incision length for decompression and interbody fusion, estimated blood loss (EBL), and 1-day and 3-day incision pain were significantly higher in group B than in group A (P < 0.05). The mean operative time was longer in group A than in group B (P < 0.05). The operation time of the first 10 cases (251 ± 24 min) was much longer than that of the last 16 cases (200 ± 17 min) in group A. The misplacement rate of percutaneous pedicle screw placement was higher in group B (P < 0.05). No infections of incisions and interbody or nerve root or dural injuries were found in either group A or B. No differences were found between the 2 groups in the JOA scores, ODI, leg pain VAS score, or lumbar interbody fusion rate at the 2-year follow-up. The VAS for back pain was better in group A than in group B (P < 0.05). LIMITATIONS: The PE RA -TLIF procedure is technically challenging and has a steep learning curve, and the study was not strictly randomized. CONCLUSION: PE RA-TLIF is a safe and effective procedure that can significantly improve the accuracy of pedicle screw placement, reduce surgical trauma, and facilitate rapid postoperative recovery. However, this technique has a steep and long learning curve and requires long-term follow-ups.


Assuntos
Robótica , Fusão Vertebral , Espondilolistese , Humanos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Prospectivos , Estudos Retrospectivos , Fusão Vertebral/métodos , Espondilolistese/cirurgia , Resultado do Tratamento
9.
Front Endocrinol (Lausanne) ; 12: 711991, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589056

RESUMO

Purpose: Congenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms via a candidate gene-based mutational burden analysis. Methods: We retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis. Results: In 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (NF1 [c.2329T>A, c.7131C>G], GHRHR [c.731G>A], STAT5B [c.1102delC], HRAS [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that POLR3A (p = 0.005), SUFU (p = 0.006), LHX3 (p = 0.021) and CREB3L4 (p = 0.040) represented top genes enriched in GHD patients. Conclusion: Our study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.


Assuntos
Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/genética , Sequenciamento Completo do Exoma , Criança , Pré-Escolar , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , DNA/sangue , Análise Mutacional de DNA , Feminino , Humanos , Fator de Crescimento Insulin-Like I/genética , Proteínas com Homeodomínio LIM/genética , Masculino , RNA Polimerase III/genética , Proteínas Repressoras/genética , Estudos Retrospectivos , Fatores de Transcrição/genética
10.
Global Spine J ; : 21925682211039186, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34409875

RESUMO

STUDY DESIGN: Retrospective. OBJECTIVES: To present rarely reported complex fractures of the upper cervical spine (C1-C2) and discuss the clinical results of the posterior temporary C1-2 pedicle screws fixation for C1-C2 stabilization. METHODS: A total of 19 patients were included in the study (18 males and 1 female). Their age ranged from 23 to 66 years (mean age of 39.6 years). The patients were diagnosed with complex fractures of the atlas and the axis of the upper cervical spine and underwent posterior temporary C1-2 pedicle screws fixation. The patients underwent a serial postoperative clinical examination at approximately 3, 6, 9 months, and annually thereafter. The neck disability index (NDI) and the range of neck rotary motion were used to evaluate the postoperative clinical efficacy of the patients. RESULTS: The average operation time and blood loss were 110 ± 25 min and 50 ± 12 ml, respectively. The mean follow-up was 38 ± 11 months (range 22 to 60 months). The neck rotary motion before removal, immediately after removal, and the last follow-up were 68.7 ± 7.1°, 115.1 ± 11.7°, and 149.3 ± 8.9° (P < 0.01). The NDI scores before and after the operation were 42.7 ± 4.3, 11.1 ± 4.0 (P < 0.01), and the NDI score 2 days after the internal fixation was removed was 7.3 ± 2.9, which was better than immediately after the operation (P < 0.01), and 2 years after the internal fixation was removed. The NDI score was 2.0 ± 0.8, which was significantly better than 2 days after the internal fixation was taken out (P < 0.001). CONCLUSIONS: Posterior temporary screw fixation is a good alternative surgical treatment for unstable C1-C2 complex fractures.

11.
Mol Ther Nucleic Acids ; 24: 961-970, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34094714

RESUMO

Congenital limb malformations (CLMs) affect 1 in 500 live births. However, the value of exome sequencing (ES) for CLM is lacking. The purpose of this study was to decipher the mutational signature of CLM on an exome level. We enrolled a cohort of 66 unrelated probands (including 47 families) with CLM requiring surgical correction. ES was performed for all patients and available parental samples. A definite molecular diagnosis was achieved in 21 out of 66 (32%) patients. We identified 19 pathogenic or likely pathogenic single-nucleotide variants and three copy number variants, of which 11 variants were novel. We identified four variants of uncertain significance. Additionally, we identified RPL9 and UBA2 as novel candidate genes for CLM. By comparing the detailed phenotypic features, we expand the phenotypic spectrum of diastrophic dysplasia and chromosome 6q terminal deletion syndrome. We also found that the diagnostic rate was significantly higher in patients with a family history of CLM (p = 0.012) or more than one limb affected (p = 0.034). Our study expands our understanding of the mutational and phenotypic spectrum of CLM and provides novel insights into the genetic basis of these syndromes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34075012

RESUMO

STUDY DESIGN: Prospective study. OBJECTIVE: The aim of this study was to prospectively assess the clinical outcomes of modified MIS-TLIF for the treatment of single-segment lumbar spondylolisthesis. SUMMARY OF BACKGROUND DATA: MIS-TLIF is a safe and effective procedure in the treatment of lumbar degenerative disease. To avoid durotomy and nerve root injury, we modified the surgical order of MIS-TLIF such that the interbody fusion procedure was performed before the decompression procedure. METHODS: One hundred thirty-nine patients with single-segment lumbar spondylolisthesis were separated into two groups. 67 patients underwent modified MIS-TLIF (group A). In group B, 72 patients underwent routine MIS-TLIF. The Japanese Orthopaedic Association (JOA) score and the visual analogue scale (VAS) scores for lower back pain (LBP) and leg pain were assessed during the postoperative follow-up, and the lumbar interbody fusion rate was evaluated by CT scanning. RESULTS: The mean operative time, incision length, average blood loss and incision pain level were not significantly different (P > 0.05) between the two groups. No nerve root or dural injuries were observed in group A. In group B, there were 2 cases of dural injury and 3 cases of nerve root injury. One patient experienced temporary numbness and weakness on dorsiflexion of the foot, which recovered in three months. No differences were identified between the two groups when postoperative JOA scores, back pain, leg pain VAS scores or the lumbar interbody fusion rate. CONCLUSION: Both methods are effective in the treatment of lumbar degenerative disease. Modified MIS-TLIF is a safe and effective procedure that can significantly reduce the occurrence of injury to the dura and nerve root during decompression and the interbody fusion procedure.Level of Evidence: 3.

13.
BMC Musculoskelet Disord ; 22(1): 483, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034738

RESUMO

INTRODUCTION: Adult non-degenerative scoliosis accounts for 90% of spinal deformities in young adults. However, perioperative complications and related risk factors of long posterior instrumentation and fusion for the treatment of adult non-degenerative scoliosis have not been adequately studied. METHODS: We evaluated clinical and radiographical results from 146 patients with adult non-degenerative scoliosis who underwent long posterior instrumentation and fusion. Preoperative clinical data, intraoperative variables, and perioperative radiographic parameters were collected to analyze the risk factors for perioperative complications. Potential and independent risk factors for perioperative complications were evaluated by univariate analysis and logistic regression analysis. RESULTS: One hundred forty-six adult non-degenerative scoliosis patients were included in our study. There were 23 perioperative complications for 21 (14.4%) patients, eight of which were cardiopulmonary complications, two of which were infection, six of which were neurological complications, three of which were gastrointestinal complications, and four of which were incision-related complication. The independent risk factors for development of total perioperative complications included change in Cobb angle (odds ratio [OR] = 1.085, 95% CI = 1.035 ~ 1.137, P = 0.001) and spinal osteotomy (OR = 3.565, 95% CI = 1.039 ~ 12.236, P = 0.043). The independent risk factor for minor perioperative complications is change in Cobb angle (OR = 1.092, 95% CI = 1.023 ~ 1.165, P = 0.008). The independent risk factors for major perioperative complications are spinal osteotomy (OR = 4.475, 95% CI = 1.960 ~ 20.861, P = 0.036) and change in Cobb angle (OR = 1.106, 95% CI = 1.035 ~ 1.182, P = 0.003). CONCLUSIONS: Our study indicate that change in Cobb angle and spinal osteotomy are independent risk factors for total perioperative complications after long-segment posterior instrumentation and fusion in adult non-degenerative scoliosis patients. Change in Cobb angle is an independent risk factor for minor perioperative complications. Change in Cobb angle and spinal osteotomy are independent risk factors for major perioperative complications.


Assuntos
Escoliose , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Radiografia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Resultado do Tratamento , Adulto Jovem
14.
World Neurosurg ; 151: e128-e136, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33831616

RESUMO

BACKGROUND: Hypertrophy of the ligamentum flavum (LF) contributes to the development of spinal stenosis. Smad proteins can mediate the fibrogenesis activity through the transforming growth factor ß1 (TGF-ß1) pathway, but which Smad protein plays a more important role in the hypertrophy process of LF is unclear. METHODS: The LF samples were obtained from 50 patients. After the LF cells (LFCs) were cultured, small interfering ribonucleic acid (siRNA) that target human phosphorylated-Smad2, 3, or 4 (p-Smad2,3,4) genes was transfected into LFCs. Next, proteins from cells were extracted and the protein levels of Smad2, Smad3, and Smad4 were detected by Western blot. The messenger ribonucleic acid level of TGF-ß1 was measured by real-time polymerase chain reaction (PCR). Furthermore, an enzyme-linked immunosorbent assay was performed to test the impact of Smad2 downstream of the TGF-ß1 signaling pathway. RESULTS: Degeneration of the LF was characterized by an increase in disorganized elastic fibers and fibrotic transformation by extracellular collagen deposition. The gene expression analysis of fibrotic genes in LFCs showed that knockdown of phosphorylated-Smad2 by siRNA significantly reduced the protein expression level of TGF-ß1 compared with other groups. The enzyme-linked immunosorbent assay suggested that the protein expression level of Smad2 can influence the downstream events of TGF-ß1 signaling pathway in the LFCs. CONCLUSIONS: Our findings suggest that Smad2 plays a potential role in the pathologic development of hypertrophy of LF. We also found that Smad2 knockdown by Smad-siRNA can influence the TGF-ß1 signaling pathway through decreasing expression of TGF-ß1, tumor necrosis factor α, and nuclear factor κb.


Assuntos
Ligamento Amarelo/patologia , Proteína Smad2/genética , Fator de Crescimento Transformador beta1 , Adulto , Idoso , Colágeno/metabolismo , Feminino , Fibroblastos/patologia , Fibrose , Humanos , Hipertrofia , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , RNA Interferente Pequeno/genética , Transdução de Sinais , Proteína Smad3/genética , Proteína Smad4/genética , Transfecção
15.
World Neurosurg ; 149: e785-e793, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33529764

RESUMO

OBJECTIVE: To report the clinical use of uniplanar cannulated pedicle screws for the correction of Lenke type 1 adolescent idiopathic scoliosis (AIS), and to evalute its safety and clinical outcomes. METHODS: A total of 68 patients with Lenke type 1 AIS were retrospective analyzed, among which 38 patients were treated with uniplanar cannulated screws at the concave side of periapical levels and multiaxial screws at the other levels (group A). The remaining 30 patients were treated with all multiaxial screws (group B). The preoperative and postoperative radiographic parameters, axial vertebral rotation, and the safety of the pedicle screws were evaluated. RESULTS: Preoperative data were comparable between the 2 groups. The postoperative proximal thoracic curve, main thoracic curve, thoracolumbar/lumbar curve, and apical vertebral rotation were significantly improved in both groups (P < 0.05). The coronal correction rates in group A and B were 83% and 81.9% (P = 0.723). The derotation rates in group A and B were 60.8% and 43.2% (P < 0.05). The rotation classification in the group A was also better than group B. The misplacement rate in group A and B was 7.9% and 11.8% (P < 0.05), and the total misplacement rate on the concave side (11.4%) was higher than that of convex side (8.4%). On the concave side, the misplacement rate in group A and B was 9.7% and 12.3%. On the convex side, the misplacement rate in group A and B was 5.9% and 11.1% (P < 0.05). CONCLUSIONS: Collectively, uniplanar cannulated pedicle screws could effectively increase the accuracy of pedicle screws and facilitate the derotation of the apical vertebra compared with the multiaxial pedicle screws.


Assuntos
Cifose/cirurgia , Parafusos Pediculares , Escoliose/cirurgia , Vértebras Torácicas/cirurgia , Adolescente , Feminino , Humanos , Masculino , Parafusos Pediculares/efeitos adversos , Período Pós-Operatório , Rotação , Fusão Vertebral/métodos , Resultado do Tratamento
16.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
17.
J Med Genet ; 58(1): 41-47, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381727

RESUMO

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.


Assuntos
Predisposição Genética para Doença , Escoliose/diagnóstico , Escoliose/genética , Adolescente , Adulto , Idade de Início , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Exoma/genética , Feminino , Humanos , Masculino , Estudos Retrospectivos , Escoliose/classificação , Escoliose/patologia , Sequenciamento Completo do Exoma
18.
J Neurosurg Case Lessons ; 1(24): CASE21134, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35855094

RESUMO

BACKGROUND: Atlantoaxial dislocation (AAD) is a rare and potentially life-threatening condition. Various underlying mechanisms of injury are described in the literature. Here, the authors report an unusual nontraumatic injury mechanism of AAD in a 12-year-old patient. OBSERVATIONS: A 12-year-old boy presented with intolerable neck pain and numbness in both upper limbs. The patient's symptoms had started 2 months after the initiation of online classes during the coronavirus disease 2019 pandemic without a history of trauma. He used a computer for personal study and online classes for prolonged hours with no respite. On physical and radiological evaluation, he was diagnosed with AAD. Before surgery, skull traction was applied to reduce the dislocation and posterior C1 lateral mass screw and C2 pedicle screw fixation was performed. An optimal clinical outcome was achieved with no postoperative complications. A preoperative visual analog scale score of 8.0 was reduced to 0 postoperatively. LESSONS: A prolonged fixed neck posture is an unusual underlying cause of AAD. Posterior C1 lateral mass and C2 pedicle screw fixation results in an optimal clinical outcome.

19.
Orphanet J Rare Dis ; 15(1): 288, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054853

RESUMO

BACKGROUND: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly. RESULTS: We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients' blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype-phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005). CONCLUSIONS: Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly.


Assuntos
Deformidades Congênitas dos Membros , Mosaicismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Dedos/anormalidades , Humanos , Mutação/genética , Proteínas Proto-Oncogênicas c-akt/genética
20.
Orphanet J Rare Dis ; 15(1): 250, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933559

RESUMO

BACKGROUND: We previously reported a novel clinically distinguishable subtype of congenital scoliosis (CS), namely, TBX6-associated congenital scoliosis (TACS). We further developed the TBX6-associated CS risk score (TACScore), a multivariate phenotype-based model to predict TACS according to the patient's clinical manifestations. In this study, we aimed to evaluate whether using the TACScore as a screening method prior to performing whole-exome sequencing (WES) is more cost-effective than using WES as the first-line genetic test for CS. METHODS: We retrospectively collected the molecular data of 416 CS patients in the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study. A decision tree was constructed to estimate the cost and the diagnostic time required for the two alternative strategies (TACScore versus WES). Bootstrapping simulations and sensitivity analyses were performed to examine the distributions and robustness of the estimates. The economic evaluation considered both the health care payer and the personal budget perspectives. RESULTS: From the health care payer perspective, the strategy of using the TACScore as the primary screening method resulted in an average cost of $1074.2 (95%CI: $1044.8 to $1103.5) and an average diagnostic duration of 38.7d (95%CI: 37.8d to 39.6d) to obtain a molecular diagnosis for each patient. In contrast, the corresponding values were $1169.6 (95%CI: $1166.9 to $1172.2) and 41.4d (95%CI: 41.1d to 41.7d) taking WES as the first-line test (P < 0.001). From the personal budget perspective, patients who were predicted to be positive by the TACScore received a result with an average cost of $715.1 (95%CI: $594.5 to $835.7) and an average diagnostic duration of 30.4d (95%CI: 26.3d to 34.6d). Comparatively, the strategy of WES as the first-line test was estimated to have significantly longer diagnostic time with an average of 44.0d (95%CI: 43.2d to 44.9d), and more expensive with an average of $1193.4 (95%CI: $1185.5 to $1201.3) (P < 0.001). In 100% of the bootstrapping simulations, the TACScore strategy was significantly less costly and more time-saving than WES. The sensitivity analyses revealed that the TACScore strategy remained cost-effective even when the cost per WES decreased to $8.8. CONCLUSIONS: This retrospective study provides clinicians with economic evidence to integrate the TACScore into clinical practice. The TACScore can be considered a cost-effective tool when it serves as a screening test prior to performing WES.


Assuntos
Escoliose , Proteínas com Domínio T , Análise Custo-Benefício , Testes Genéticos , Humanos , Estudos Retrospectivos , Fatores de Risco , Escoliose/diagnóstico , Escoliose/genética , Proteínas com Domínio T/genética
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