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1.
Spine (Phila Pa 1976) ; 49(7): 506-512, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37093030

RESUMO

STUDY DESIGN: Prospective randomized. OBJECTIVE: Intraoperative methylprednisolone is a common adjunct following microscopic laminectomy/microdiscectomy. The goal of epidural instillation is a rapid symptomatic reduction in irritation of neural elements. There is inconsistent data supporting its use intraoperatively. To understand whether this maneuver results in any clinical effect, we performed a multiyear prospective study. SUMMARY OF BACKGROUND DATA: Previous work has demonstrated equivocal effects on pain with a suggestion of an increased risk of complication. These studies tend to suffer from small sample sizes and short follow-ups. MATERIALS AND METHODS: Study obtained IRB approval. During the study period from 2013 to 2019, nearly equivalent numbers of patients who had received steroids during MIS decompressions were followed. Primary outcomes included pain (visual analog scale) and disability [Oswestry Disability Index (ODI)] at 2 weeks and 4 months. Secondary outcomes included complications, readmissions, and reoperation rates during the study period. RESULTS: Four hundred eighty-six patients were followed for a mean follow-up of 5.17 years. The index case was more likely to be a revision surgery in the steroid group. Across all patients, there was no difference in pain at 2 weeks or 4 months. Disability was reduced at 2 weeks in the steroid group (ODI: 16.71 vs . 21.02, P = 0.04) but not at 4 months. By subgroup analysis, this is largely explained by ODI reduction in patients with high preoperative ODI (13.00 vs . 43.43, P = 0.03). Patients in the steroid cohort were more likely to undergo subsequent spinal surgery during the study period. CONCLUSION: Methylprednisolone instillation is associated with a large, transient reduction in ODI for patients with high preoperative ODI; there is no measurable effect on pain. There is equivocal effect on risk of subsequent reoperation. This issue was clarified in peer review but changes did not make it to the abstract. Therefore, the technique is likely best reserved for patients with significant preoperative disability.


Assuntos
Vértebras Lombares , Estenose Espinal , Humanos , Estudos Prospectivos , Resultado do Tratamento , Vértebras Lombares/cirurgia , Metilprednisolona/uso terapêutico , Discotomia , Dor/cirurgia , Estudos Retrospectivos , Descompressão , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estenose Espinal/cirurgia
2.
J Clin Med ; 12(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38137663

RESUMO

INTRODUCTION: In a multilevel cervical laminoplasty operation for patients with cervical spondylotic myelopathy (CSM), a partial or complete C3 laminectomy may be performed at the upper level instead of a C3 plated laminoplasty. It is unknown whether C3 technique above the laminoplasty affects loss of cervical lordosis or range of motion. METHODS: Patients undergoing multilevel laminoplasty of the cervical spine (C3-C6/C7) at a single institution were retrospectively reviewed. Patients were divided into two cohorts based on surgical technique at C3: C3-C6/C7 plated laminoplasty ("C3 laminoplasty only", N = 61), C3 partial or complete laminectomy, plus C4-C6/C7 plated laminoplasty (N = 39). All patients had at least 1-year postoperative X-ray treatment. RESULTS: Of 100 total patients, C3 laminoplasty and C3 laminectomy were equivalent in all demographic data, except for age (66.4 vs. 59.4 years, p = 0.012). None of the preoperative radiographic parameters differed between the C3 laminoplasty and C3 laminectomy cohorts: cervical lordosis (13.1° vs. 11.1°, p = 0.259), T1 slope (32.9° vs. 29.2°, p = 0.072), T1 slope-cervical lordosis (19.8° vs. 18.6°, p = 0.485), or cervical sagittal vertical axis (3.1 cm vs. 2.7 cm, p = 0.193). None of the postoperative radiographic parameters differed between the C3 laminoplasty and C3 laminectomy cohorts: cervical lordosis (9.4° vs. 11.2°, p = 0.369), T1 slope-cervical lordosis (21.7° vs. 18.1°, p = 0.126), to cervical sagittal vertical axis (3.3 cm vs. 3.6 cm, p = 0.479). In the total cohort, 31% had loss of cervical lordosis >5°. Loss of lordosis reached 5-10° (mild change) in 13% of patients and >10° (moderate change) in 18% of patients. C3 laminoplasty and C3 laminectomy cohorts did not differ with respect to no change (<5°: 65.6% vs. 74.3%, respectively), mild change (5-10°: 14.8% vs. 10.3%), and moderate change (>10°: 19.7% vs. 15.4%) in cervical lordosis, p = 0.644. When controlling for age, ordinal regression showed that surgical technique at C3 did not increase the odds of postoperative loss of cervical lordosis. C3 laminectomy versus C3 laminoplasty did not differ in the postoperative range of motion on cervical flexion-extension X-rays (23.9° vs. 21.7°, p = 0.451, N = 91). CONCLUSION: There was no difference in postoperative loss of cervical lordosis or postoperative range of motion in patients who underwent either C3-C6/C7 plated laminoplasty or C3 laminectomy plus C4-C6/C7 plated laminoplasty.

3.
PLoS Genet ; 19(8): e1010589, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37552671

RESUMO

The double stranded RNA binding protein Adad1 (adenosine deaminase domain containing 1) is a member of the adenosine deaminase acting on RNAs (Adar) protein family with germ cell-specific expression. In mice, Adad1 is necessary for sperm differentiation, however its function outside of mammals has not been investigated. Here, through an N-ethyl-N-nitrosourea (ENU) based forward genetic screen, we identified an adad1 mutant zebrafish line that develops as sterile males. Further histological examination revealed complete lack of germ cells in adult mutant fish, however germ cells populated the gonad, proliferated, and entered meiosis in larval and juvenile fish. Although meiosis was initiated in adad1 mutant testes, the spermatocytes failed to progress beyond the zygotene stage. Thus, Adad1 is essential for meiosis and germline maintenance in zebrafish. We tested if spermatogonial stem cells were affected using nanos2 RNA FISH and a label retaining cell (LRC) assay, and found that the mutant testes had fewer LRCs and nanos2-expressing cells compared to wild-type siblings, suggesting that failure to maintain the spermatogonial stem cells resulted in germ cell loss by adulthood. To identify potential molecular processes regulated by Adad1, we sequenced bulk mRNA from mutants and wild-type testes and found mis-regulation of genes involved in RNA stability and modification, pointing to a potential broader role in post-transcriptional regulation. Our findings suggest that the RNA regulatory protein Adad1 is required for fertility through regulation of spermatogonial stem cell maintenance in zebrafish.


Assuntos
Adenosina Desaminase , Peixe-Zebra , Animais , Masculino , Camundongos , Adenosina Desaminase/metabolismo , Células Germinativas/metabolismo , Mamíferos/genética , Meiose/genética , RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Sêmen/metabolismo , Testículo/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
4.
J Neurosurg Spine ; 39(2): 287-294, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148234

RESUMO

OBJECTIVE: In the absence of spinal cord compression, it is unclear if surgery is more effective than radiation treatment for improving functional outcomes in metastatic spinal tumor patients with potentially unstable spines. The authors compared functional status outcomes assessed with Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) scores after surgery or radiation in patients without spinal cord compression with Spine Instability Neoplastic Score (SINS) values of 7-12 indicating possible instability (SINS 7-12). METHODS: A retrospective review was performed of patients with metastatic spinal tumor SINS values of 7-12 at a single institution between 2004 and 2014. Patients were divided into two different groups: 1) those treated with surgery and 2) those treated with radiation. Baseline clinical characteristics were measured, and KPS and ECOG scores were obtained pre- and postradiation or postsurgery. The paired, nonparametric Wilcoxon signed-rank test and ordinal logistic regression analysis were used for statistical analysis. RESULTS: A total of 162 patients met inclusion criteria; 63 patients were treated operatively and 99 patients were treated with radiation. The mean follow-up was 1.9 years, with a median of 1.1 years for the surgical cohort (ranging from 2.5 months to 13.8 years) and a mean of 2 years with a median of 0.8 years for the radiation cohort (ranging from 2 months to 9.3 years). After covariates were accounted for, the average posttreatment changes in KPS scores in the surgical cohort were 7.46 ± 17.3 and in the radiation cohort were -2 ± 13.6 (p = 0.045). No significant difference was observed in ECOG scores. KPS scores improved postoperatively in 60.3% of patients in the surgical group and postradiation in 32.3% of patients in the radiation cohort (p < 0.001). Subanalysis within the radiation cohort revealed no differences in fracture rates or local control between patients treated with external-beam radiation therapy versus stereotactic body radiation therapy. In patients initially treated with radiation, 21.2% eventually developed compression fractures at a treated level. Five of the 99 patients in the radiation cohort-all of whom had a fracture-eventually underwent either methyl methacrylate augmentation or instrumented fusion. CONCLUSIONS: Patients with SINS values of 7-12 who underwent surgery had greater improvement in KPS scores-but not in ECOG scores-than patients undergoing radiation alone. In patients treated with radiation, treatment was converted to a procedural intervention such as surgery only in patients who sustained fractures. Of the patients with fractures after radiation (21 of 99), 5 patients underwent an invasive procedure and 16 did not.


Assuntos
Neoplasias do Sistema Nervoso Central , Fraturas por Compressão , Compressão da Medula Espinal , Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/radioterapia , Compressão da Medula Espinal/cirurgia , Coluna Vertebral/cirurgia , Neoplasias da Medula Espinal/patologia , Estudos Retrospectivos
5.
J Neurosurg Spine ; 38(2): 265-270, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36461846

RESUMO

OBJECTIVE: Wound complications are a common adverse event following metastatic spine tumor surgery. Some patients with spinal metastases may first undergo radiation but eventually require spinal surgery because of either cord compression or instability. The authors compared wound complication rates in patients who had undergone surgery for metastatic disease and received preoperative radiation treatments, postoperative radiation, or no radiation. METHODS: Records from patients treated at the University of California, San Francisco, for metastatic spine disease between 2005 and 2017 were retrospectively reviewed. Baseline characteristics were collected, including preoperative Karnofsky Performance Status (KPS), Spine Instability Neoplastic Score, total radiation dose, indication for surgery, diabetes status, time between radiation and surgery, use of perioperative chemotherapy or steroids, estimated blood loss, extent of fusion, and preoperative albumin level. Wound complication was defined as poor healing, dehiscence, or infection per the Centers for Disease Control and Prevention guidelines, within 6 months of surgery. One-way ANOVA was used to compare means across groups. Cumulative incidence analysis with competing risk methodology was used to adjust for risk of death during follow-up. Statistical analysis was performed using R software. RESULTS: Two hundred five patients with adequate medical records were identified. Seventy patients had received preoperative radiation, 74 had received postoperative radiation within 6 months after surgery, and 61 had received no radiation at the surgical site. Wound complication rates were similar across the 3 cohorts: 14.3% (n = 10) in the group with preoperative radiation, 10.8% (n = 8) in the group that received postoperative radiation, and 11.5% (n = 7) in the group with no radiation (p = 0.773). Competing risk analysis showed a higher cumulative incidence of wound complications for the preoperative cohort, though this difference was not significant (p = 0.46). Overall, 89 patients were treated with external beam radiation therapy (EBRT), whereas 55 received stereotactic body radiation therapy (SBRT). There was no significant difference in wound complications for patients treated with EBRT (11.2%, n = 10) versus SBRT (14.5%, n = 8; p = 0.825). KPS was the only factor correlated with wound complications on univariate analysis (p = 0.03). CONCLUSIONS: Wound complication rates did not differ across the 3 cohorts: patients treated with preoperative radiation, postoperative radiation within 6 months of surgery, or no radiation. The effect size was small for KPS and likely does not represent a clinically significant predictor of wound complications.


Assuntos
Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , Compressão da Medula Espinal/cirurgia , Medição de Risco , Complicações Pós-Operatórias/epidemiologia
6.
Global Spine J ; 13(4): 1042-1048, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-33998302

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Overcorrection in adult spinal deformity (ASD) surgery may lead to proximal junctional kyphosis (PJK) because of posterior spinal displacement. The aim of this paper is to determine if the L1 position relative to the gravity line (GL) is associated with PJK. METHODS: ASD patients fused from the lower thoracic spine to sacrum by 4 spine surgeons at our hospital were retrospectively studied. Lumbar-only and upper thoracic spine fusions were excluded. Spinopelvic parameters, the L1 plumb line (L1PL), L1 distance to the GL (L1-GL), and Roussouly type were measured. RESULTS: One hundred fourteen patients met inclusion criteria (63 patients with PJK, 51 without). Mean age and follow up was 65.51 and 3.39 years, respectively. There was no difference between the PJK and the non-PJK groups in baseline demographics, pre-operative and immediate post-operative pelvic incidence-lumbar lordosis mismatch, sagittal vertical axis, or coronal Cobb. The immediate postoperative L1-GL was -7.24 cm in PJK and -3.45 cm in non-PJK (P < 0.001), L1PL was 1.71 cm in PJK and 3.07 cm in non-PJK (P = 0.004), and PT (23.76° vs 18.90°, P = 0.026) and TK (40.56° vs 31.39°, P < 0.001) were larger in PJK than in non-PJK. After univariate and multivariate analyses, immediate postoperative TK and immediate postoperative L1-GL were independent risk factors for PJK without collinearity. CONCLUSIONS: A dorsally displaced L1 relative to the GL was associated with an increased risk of PJK after ASD surgery. The postoperative L1-GL distance may be a factor to consider during ASD surgery.

7.
World Neurosurg ; 167: e464-e468, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35964902

RESUMO

OBJECTIVE: We sought to evaluate Hounsfield units (HU) at the adjacent segment after single-level transforaminal lumbar interbody fusion (TLIF) with preoperative and postoperative computed tomography scans. METHODS: We performed a retrospective study on a series of patients who underwent L4-5 TLIF, from 2007 to 2017, by 3 spine surgeons at our institution. One-hundred and forty-three total patients were identified, and 41 patients with minimum 1-year follow-up met inclusion criteria. HU values were measured on preoperative and postoperative computed tomography at the adjacent L3 segment and at L1 as a control arm. Lumbar lordosis, pelvic tilt, pelvic incidence, sacral slope, and sagittal vertical axis were also collected preoperatively and postoperatively. RESULTS: Mean preoperative HU value at L3 did not differ from the postoperative value (134.11 ± 47.14 mg/cm3 vs. 141.21 ± 55.14 mg/cm3, P = 0.34). Similarly, the mean preoperative HU value at the L1 control level region of interest did not differ from the postoperative value (150.17 ± 53.91 mg/cm3 vs. 145.78 ± 58.34 mg/cm3, P = 0.634). The interrater reliability of HU measurements was satisfactory with a resulting intraclass correlation coefficient of 0.76. CONCLUSIONS: As measured by HU, we did not observe a change in bone density or other signs of adjacent segment disease at the L3 vertebral body 12 months after L4-5 TLIF. Spinopelvic parameters were not shown to be correlated with HU changes.


Assuntos
Densidade Óssea , Fusão Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Corpo Vertebral , Reprodutibilidade dos Testes , Fusão Vertebral/métodos
9.
Spine Deform ; 10(2): 449-455, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478128

RESUMO

INTRODUCTION: Although matching lumbar lordosis (LL) with pelvic incidence (PI) is an important surgical goal for adult spinal deformity (ASD), there is concern that overcorrection may lead to proximal junctional kyphosis (PJK). We introduce the upper instrumented vertebra-femoral angle (UIVFA) as a measure of appropriate postoperative position in the setting of lower thoracic to pelvis surgical correction for patients with sagittal imbalance. We hypothesize that a more posterior UIV position in relation to the center of the femoral head is associated with an increased risk of PJK given compensatory hyperkyphosis above the UIV. METHODS: In this retrospective cohort study, adult patients undergoing lower thoracic (T9-T12) to pelvis correction of ASD with a minimum of 2-year follow-up were included. UIVFA was measured as the angle subtended by a line from the UIV centroid to the femoral head center to the vertical axis. Patients who developed PJK and those who did not were compared with preoperative and postoperative UIVFA as well as change between postoperative and preoperative UIVFA (deltaUIVFA). RESULTS: Of 119 patients included with an average 3.6-year follow-up, 51 (42.9%) had PJK and 24 (20.2%) had PJF. Patients with PJK had significantly higher postoperative UIVFA (12.6 ± 4.8° vs. 9.4 ± 6.6°, p = 0.04), deltaUIVFA (6.1 ± 7.6° vs. 2.1 ± 5.6°, p < 0.01), postoperative pelvic tilt (27.3 ± 9.2 vs. 23.3 ± 11, p = 0.04), postoperative lumbar lordosis (47.7 ± 13.9° vs. 42.4 ± 13.1, p = 0.04) and postoperative thoracic kyphosis (44.9 ± 13.2 vs. 31.6 ± 18.8) than patients without PJK. With multivariate logistic regression, postoperative UIVFA and deltaUIVFA were found to be independent risk factors for PJK (p < 0.05). DeltaUIVFA was found to be an independent risk factor for PJF (p < 0.05). A receiver operating characteristic (ROC) curve for UIVFA as a predictor for PJK was established with an area under the curve of 0.67 (95% CI 0.59-0.76). Per the Youden index, the optimal UIVFA cut-off value is 11.5 degrees. CONCLUSION: The more posterior the UIV is from the femoral head center after lower thoracic to pelvis surgical correction for ASD, the more patients are at risk for PJK. The greater the magnitude of posterior translation of the UIV from the femoral head center from preop to postop, the greater the likelihood for PJF.


Assuntos
Cifose , Fusão Vertebral , Adulto , Humanos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia
10.
Clin Spine Surg ; 35(1): E181-E186, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029263

RESUMO

STUDY DESIGN: This was a retrospective, single center. OBJECTIVES: The objective of this study was to investigate the association between the cross-sectional area (CSA) of the deep extensor muscles (DEM) and postlaminoplasty alignment. SUMMARY OF BACKGROUND DATA: The preoperative CSA of the semispinalis cervicis (SC) has been reported to correlate with loss of lordosis (LL) after laminoplasty, with a CSA <154.5 mm2 associated with a 10 degrees LL. METHODS: Laminoplasty patients at the University of California San Francisco between 2009 and 2018 by 2 spine surgeons were retrospectively studied. Patients with previous cervical surgery or nondegenerative diagnoses were excluded. Measurements included the C2-C7 Cobb, T1 slope, and cervical sagittal vertical axis. Preoperative DEM CSA was measured on magnetic resonance imaging. Variables associated with lordosis were analyzed with univariate analysis and multivariate logistic regression, and association between postoperative cervical alignment and the musculature was evaluated. RESULTS: Seventy-six patients with a mean age of 64 years were included. The average follow-up was 22.53 months. The overall average CSA of the DEM was 2274.55 mm2 and that of the SC was 275.64 mm2. Means of both CSAs were higher in men (P<0.001). Linear regression showed no correlation between LL with CSA of the DEM or the SC (r=0.005, P=0.119; r=0.001, P=0.095). Univariate and multivariate regression showed no differences in the CSA of the DEM and SC between groups with and without LL (P=0.092, 0.117 and 0.163, 0.292). There was no correlation in LL with sex or body mass index (P>0.05). CONCLUSIONS: Preoperative CSA of the deep cervical extensor muscles may not predict LL after cervical laminoplasty. The correlation between the preoperative SC CSA and postoperative cervical alignment may not be as strong as previously reported.


Assuntos
Laminoplastia , Lordose , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Laminoplastia/efeitos adversos , Laminoplastia/métodos , Lordose/diagnóstico por imagem , Lordose/cirurgia , Masculino , Pessoa de Meia-Idade , Músculos , Estudos Retrospectivos , Resultado do Tratamento
11.
Neurosurg Focus ; 51(6): E2, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34852318

RESUMO

OBJECTIVE: There is a learning curve for surgeons performing "awake" spinal surgery. No comprehensive guidelines have been proposed for the selection of ideal candidates for awake spinal fusion or decompression. The authors sought to formulate an algorithm to aid in patient selection for surgeons who are in the startup phase of awake spinal surgery. METHODS: The authors developed an algorithm for selecting patients appropriate for awake spinal fusion or decompression using spinal anesthesia supplemented with mild sedation and local analgesia. The anesthetic protocol that was used has previously been reported in the literature. This algorithm was formulated based on a multidisciplinary team meeting and used in the first 15 patients who underwent awake lumbar surgery at a single institution. RESULTS: A total of 15 patients who underwent decompression or lumbar fusion using the awake protocol were reviewed. The mean patient age was 61 ± 12 years, with a median BMI of 25.3 (IQR 2.7) and a mean Charlson Comorbidity Index of 2.1 ± 1.7; 7 patients (47%) were female. Key patient inclusion criteria were no history of anxiety, 1 to 2 levels of lumbar pathology, moderate stenosis and/or grade I spondylolisthesis, and no prior lumbar surgery at the level where the needle is introduced for anesthesia. Key exclusion criteria included severe and critical central canal stenosis or patients who did not meet the inclusion criteria. Using the novel algorithm, 14 patients (93%) successfully underwent awake spinal surgery without conversion to general anesthesia. One patient (7%) was converted to general anesthesia due to insufficient analgesia from spinal anesthesia. Overall, 93% (n = 14) of the patients were assessed as American Society of Anesthesiologists class II, with 1 patient (7%) as class III. The mean operative time was 115 minutes (± 60 minutes) with a mean estimated blood loss of 46 ± 39 mL. The median hospital length of stay was 1.3 days (IQR 0.1 days). No patients developed postoperative complications and only 1 patient (7%) required reoperation. The mean Oswestry Disability Index score decreased following operative intervention by 5.1 ± 10.8. CONCLUSIONS: The authors propose an easy-to-use patient selection algorithm with the aim of assisting surgeons with patient selection for awake spinal surgery while considering BMI, patient anxiety, levels of surgery, and the extent of stenosis. The algorithm is specifically intended to assist surgeons who are in the learning curve of their first awake spinal surgery cases.


Assuntos
Fusão Vertebral , Vigília , Idoso , Algoritmos , Feminino , Humanos , Curva de Aprendizado , Pessoa de Meia-Idade , Seleção de Pacientes
12.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607954

RESUMO

BRCA1 germline mutations are associated with an increased risk of breast and ovarian cancer. Recent findings of others suggest that BRCA1 mutation carriers also bear an increased risk of esophageal and gastric cancer. Here, we employ a Brca1/Trp53 mouse model to show that unresolved replication stress (RS) in BRCA1 heterozygous cells drives esophageal tumorigenesis in a model of the human equivalent. This model employs 4-nitroquinoline-1-oxide (4NQO) as an RS-inducing agent. Upon drinking 4NQO-containing water, Brca1 heterozygous mice formed squamous cell carcinomas of the distal esophagus and forestomach at a much higher frequency and speed (∼90 to 120 d) than did wild-type (WT) mice, which remained largely tumor free. Their esophageal tissue, but not that of WT control mice, revealed evidence of overt RS as reflected by intracellular CHK1 phosphorylation and 53BP1 staining. These Brca1 mutant tumors also revealed higher genome mutation rates than those of control animals; the mutational signature SBS4, which is associated with tobacco-induced tumorigenesis; and a loss of Brca1 heterozygosity (LOH). This uniquely accelerated Brca1 tumor model is also relevant to human esophageal squamous cell carcinoma, an often lethal tumor.


Assuntos
Proteína BRCA1/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Perda de Heterozigosidade/genética , Proteína Supressora de Tumor p53/genética , 4-Nitroquinolina-1-Óxido/toxicidade , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Quinase 1 do Ponto de Checagem/metabolismo , Modelos Animais de Doenças , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/induzido quimicamente , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Mutação em Linhagem Germinativa/genética , Heterozigoto , Humanos , Perda de Heterozigosidade/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
13.
J Neurosurg Spine ; : 1-8, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34534963

RESUMO

OBJECTIVE: Reduction of Meyerding grade is often performed during fusion for spondylolisthesis. Although radiographic appearance may improve, correlation with patient-reported outcomes (PROs) is rarely reported. In this study, the authors' aim was to assess the impact of spondylolisthesis reduction on 24-month PRO measures after decompression and fusion surgery for Meyerding grade I degenerative lumbar spondylolisthesis. METHODS: The Quality Outcomes Database (QOD) was queried for patients undergoing posterior lumbar fusion for spondylolisthesis with a minimum 24-month follow-up, and quantitative correlation between Meyerding slippage reduction and PROs was performed. Baseline and 24-month PROs, including the Oswestry Disability Index (ODI), EQ-5D, Numeric Rating Scale (NRS)-back pain (NRS-BP), NRS-leg pain (NRS-LP), and satisfaction (North American Spine Society patient satisfaction questionnaire) scores were noted. Multivariable regression models were fitted for 24-month PROs and complications after adjusting for an array of preoperative and surgical variables. Data were analyzed for magnitude of slippage reduction and correlated with PROs. Patients were divided into two groups: < 3 mm reduction and ≥ 3 mm reduction. RESULTS: Of 608 patients from 12 participating sites, 206 patients with complete data were identified in the QOD and included in this study. Baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts except for depression, listhesis magnitude, and the proportion with dynamic listhesis (which were accounted for in the multivariable analysis). One hundred four (50.5%) patients underwent lumbar decompression and fusion with slippage reduction ≥ 3 mm (mean 5.19, range 3 to 11), and 102 (49.5%) patients underwent lumbar decompression and fusion with slippage reduction < 3 mm (mean 0.41, range 2 to -2). Patients in both groups (slippage reduction ≥ 3 mm, and slippage reduction < 3 mm) reported significant improvement in all primary patient reported outcomes (all p < 0.001). There was no significant difference with regard to the PROs between patients with or without intraoperative reduction of listhesis on univariate and multivariable analyses (ODI, EQ-5D, NRS-BP, NRS-LP, or satisfaction). There was no significant difference in complications between cohorts. CONCLUSIONS: Significant improvement was found in terms of all PROs in patients undergoing decompression and fusion for lumbar spondylolisthesis. There was no correlation with clinical outcomes and magnitude of Meyerding slippage reduction.

14.
J Phys Chem C Nanomater Interfaces ; 125(9): 5110-5115, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-34178204

RESUMO

We have studied the dissociative adsorption of hydrogen under high coverage conditions of adsorbed hydrogen on Pd and Pt nanoislands supported on Au(111) using Density Functional Theory calculations. The results reveal that for Pd/Au(111), the free energy of hydrogen adsorption ΔG is close to 0 kJ/mol when the coverage of adsorbed hydrogen is near 1 ML, where the available catalytic sites are located at the edges of the Pd nanoislands. In the case of Pt/Au(111), ΔG ≈ 0 kJ/mol under a broad range of hydrogen coverage conditions, from 1 ML to 3 ML, depending on the size of the Pt nanoislands. This is the case because the available catalytic sites are located at both the steps and terraces of Pt nanoislands. These findings indicate that Au surfaces with Pd or Pt nanoislands offer catalytic sites with ΔG ≈ 0 for hydrogen reactions, one key factor for an ideal electrocatalyst for hydrogen reactions.

15.
Neurosurg Focus ; 50(5): E6, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932936

RESUMO

OBJECTIVE: Within the Spine Instability Neoplastic Score (SINS) classification, tumor-related potential spinal instability (SINS 7-12) may not have a clear treatment approach. The authors aimed to examine the proportion of patients in this indeterminate zone who later required surgical stabilization after initial nonoperative management. By studying this patient population, they sought to determine if a clear SINS cutoff existed whereby the spine is potentially unstable due to a lesion and would be more likely to require stabilization. METHODS: Records from patients treated at the University of California, San Francisco, for metastatic spine disease from 2005 to 2019 were retrospectively reviewed. Seventy-five patients with tumor-related potential spinal instability (SINS 7-12) who were initially treated nonoperatively were included. All patients had at least a 1-year follow-up with complete medical records. A univariate chi-square test and Student t-test were used to compare categorical and continuous outcomes, respectively, between patients who ultimately underwent surgery and those who did not. A backward likelihood multivariate binary logistic regression model was used to investigate the relationship between clinical characteristics and surgical intervention. Recursive partitioning analysis (RPA) and single-variable logistic regression were performed as a function of SINS. RESULTS: Seventy-five patients with a total of 292 spinal metastatic sites were included in this study; 26 (34.7%) patients underwent surgical intervention, and 49 (65.3%) did not. There was no difference in age, sex, comorbidities, or lesion location between the groups. However, there were more patients with a SINS of 12 in the surgery group (55.2%) than in the no surgery group (44.8%) (p = 0.003). On multivariate analysis, SINS > 11 (OR 8.09, CI 1.96-33.4, p = 0.004) and Karnofsky Performance Scale (KPS) score < 60 (OR 0.94, CI 0.89-0.98, p = 0.008) were associated with an increased risk of surgery. KPS score was not correlated with SINS (p = 0.4). RPA by each spinal lesion identified an optimal cutoff value of SINS > 10, which were associated with an increased risk of surgical intervention. Patients with a surgical intervention had a higher incidence of complications on multivariable analysis (OR 2.96, CI 1.01-8.71, p = 0.048). CONCLUSIONS: Patients with a mean SINS of 11 or greater may be at increased risk of mechanical instability requiring surgery after initial nonoperative management. RPA showed that patients with a KPS score of 60 or lower and a SINS of greater than 10 had increased surgery rates.


Assuntos
Instabilidade Articular , Neoplasias da Coluna Vertebral , Seguimentos , Humanos , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral
16.
J Neurosurg Spine ; 34(5): 741-748, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711811

RESUMO

OBJECTIVE: Minimally invasive surgery (MIS) for spinal deformity uses interbody techniques for correction, indirect decompression, and arthrodesis. Selection criteria for choosing a particular interbody approach are lacking. The authors created the minimally invasive interbody selection algorithm (MIISA) to provide a framework for rational decision-making in MIS for deformity. METHODS: A retrospective data set of circumferential MIS (cMIS) for adult spinal deformity (ASD) collected over a 5-year period was analyzed by level in the lumbar spine to identify surgeon preferences and evaluate segmental lordosis outcomes. These data were used to inform a Delphi session of minimally invasive deformity surgeons from which the algorithm was created. The algorithm leads to 1 of 4 interbody approaches: anterior lumbar interbody fusion (ALIF), anterior column release (ACR), lateral lumbar interbody fusion (LLIF), and transforaminal lumbar interbody fusion (TLIF). Preoperative and 2-year postoperative radiographic parameters and clinical outcomes were compared. RESULTS: Eleven surgeons completed 100 cMISs for ASD with 338 interbody devices, with a minimum 2-year follow-up. The type of interbody approach used at each level from L1 to S1 was recorded. The MIISA was then created with substantial agreement. The surgeons generally preferred LLIF for L1-2 (91.7%), L2-3 (85.2%), and L3-4 (80.7%). ACR was most commonly performed at L3-4 (8.4%) and L2-3 (6.2%). At L4-5, LLIF (69.5%), TLIF (15.9%), and ALIF (9.8%) were most commonly utilized. TLIF and ALIF were the most selected approaches at L5-S1 (61.4% and 38.6%, respectively). Segmental lordosis at each level varied based on the approach, with greater increases reported using ALIF, especially at L4-5 (9.2°) and L5-S1 (5.3°). A substantial increase in lordosis was achieved with ACR at L2-3 (10.9°) and L3-4 (10.4°). Lateral interbody arthrodesis without the use of an ACR did not generally result in significant lordosis restoration. There were statistically significant improvements in lumbar lordosis (LL), pelvic incidence-LL mismatch, coronal Cobb angle, and Oswestry Disability Index at the 2-year follow-up. CONCLUSIONS: The use of the MIISA provides consistent guidance for surgeons who plan to perform MIS for deformity. For L1-4, the surgeons preferred lateral approaches to TLIF and reserved ACR for patients who needed the greatest increase in segmental lordosis. For L4-5, the surgeons' order of preference was LLIF, TLIF, and ALIF, but TLIF failed to demonstrate any significant lordosis restoration. At L5-S1, the surgical team typically preferred an ALIF when segmental lordosis was desired and preferred a TLIF if preoperative segmental lordosis was adequate.

17.
Neurosurgery ; 88(6): 1088-1094, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33575788

RESUMO

BACKGROUND: Posterior cervical decompression and fusion (PCF) is a common procedure used to treat various cervical spine pathologies, but the 90-d outcomes following PCF surgery continue to be incompletely defined. OBJECTIVE: To identify risk factors associated with 90-d readmission and reoperation following PCF surgery. METHODS: Adults undergoing PCF from 2012 to 2020 were identified. Demographic and radiographic data, surgical characteristics, and 90-d outcomes were collected. Univariate analysis was performed using Student's t-test, chi square, and Fisher exact tests as appropriate. Multivariable logistic regression models with lasso penalty were used to analyze various risk factors. RESULTS: A total of 259 patients were included. The 90-d readmission and reoperation rates were 9.3% and 4.6%, respectively. The most common reason for readmission was surgical site infection (SSI) (33.3%) followed by new neurological deficits (16.7%). Patients who smoked tobacco had 3-fold greater odds of readmission compared to nonsmokers (odds ratio [OR]: 3.48; 95% CI 1.87-6.67; P = .0001). Likewise, the most common reason for reoperation was SSI (33.3%) followed by seroma and implant failure (25.0% each). Smoking was also an independent risk factor for reoperation, associated with nearly 4-fold greater odds of return to the operating room (OR: 3.53; 95% CI 1.53-8.57; P = .003). CONCLUSION: Smoking is a significant predictor of 90-d readmission and reoperation in patients undergoing PCF surgery. Smoking cessation should be strongly considered preoperatively in elective PCF cases to minimize the risk of 90-d readmission and reoperation.


Assuntos
Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Fumar/epidemiologia , Fusão Vertebral/estatística & dados numéricos , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Cirurgia de Second-Look , Infecção da Ferida Cirúrgica/etiologia
18.
Laryngoscope ; 131(4): E1349-E1356, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32886384

RESUMO

OBJECTIVES: To characterize tracheal cartilage morphology in mouse models of fibroblast growth factor receptor (Fgfr2)-related craniosynostosis syndromes. To establish relationships between specific Fgfr2 mutations and tracheal cartilaginous sleeve (TCS) phenotypes in these mouse models. METHODS: Postnatal day 0 knock-in mouse lines with disease-specific genetic variations in the Fgfr2 gene (Fgfr2C342Y/C342Y , Fgfr2C342Y/+ , Fgfr2+/Y394C , Fgfr2+/S252W , and Fgfr2+/P253R ) as well as line-specific controls were utilized. Tracheal cartilage morphology as measured by gross analyses, microcomputed tomography (µCT), and histopathology were compared using Chi-squared and single-factor analysis of variance statistical tests. RESULTS: A greater proportion of rings per trachea were abnormal in Fgfr2C342Y/+ tracheas (63%) than Fgfr2+/S252W (17%), Fgfr2+/P253R (17%), Fgfr2+/Y394C (12%), and controls (10%) (P < .001 for each vs. Fgfr2C342Y/+ ). TCS segments were found only in Fgfr2C342Y/C342Y (100%) and Fgfr2C342Y/+ (72%) tracheas. Cricoid and first-tracheal ring fusion was noted in all Fgfr2C342Y/C342Y and 94% of Fgfr2C342Y/+ samples. The Fgfr2C342Y/C342Y and Fgfr2C342Y/+ groups were found to have greater areas and volumes of cartilage than other lines on gross analysis and µCT. Histologic analyses confirmed TCS among the Fgfr2C342Y/C342Y and Fgfr2C342Y/+ groups, without appreciable differences in cartilage morphology, cell size, or density; no histologic differences were observed among other Fgfr2 lines compared to controls. CONCLUSION: This study found TCS phenotypes only in the Fgfr2C342Y mouse lines. These lines also had increased tracheal cartilage compared to other mutant lines and controls. These data support further study of the Fgfr2 mouse lines and the investigation of other Fgfr2 variants to better understand their role in tracheal development and TCS formation. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1349-E1356, 2021.


Assuntos
Estudos de Associação Genética/métodos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Traqueia/anormalidades , Doenças da Traqueia/genética , Acantose Nigricans/genética , Acrocefalossindactilia/genética , Animais , Cartilagem/patologia , Disostose Craniofacial/genética , Craniossinostoses/genética , Modelos Animais de Doenças , Orelha/anormalidades , Humanos , Camundongos , Mutação , Fenótipo , Dermatoses do Couro Cabeludo/genética , Anormalidades da Pele/genética , Traqueia/embriologia , Traqueia/patologia , Doenças da Traqueia/diagnóstico , Doenças da Traqueia/patologia , Microtomografia por Raio-X/métodos
19.
Oper Neurosurg (Hagerstown) ; 20(3): E214, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33372964

RESUMO

This surgical video demonstrates the technique for correcting degenerative cervical kyphosis using an anterior cervical discectomy and fusion (ACDF). Degenerative cervical kyphosis can cause radiculopathy, myelopathy, and difficulty holding up one's head. The goal of surgical intervention is to alleviate pain, improve the ability for upright gaze, and decompress the spinal cord or nerve roots. Posterior-only approaches and anterior corpectomies are alternative treatments to address cervical kyphosis. However, an ACDF allows for sequential induction of lordosis via distraction over multiple segments and for further lordosis induction by sequential screw tightening, pulling the spine towards a lordotic cervical plate.1 This video shows 2 cases demonstrating a technique of correcting severe cervical degenerative kyphosis. The video illustrates our initial kyphotic Caspar pin placement coupled with sequential anterior distraction to correct kyphosis. The technique is most useful in patients who have good bone density, nonankylosed facets, and degenerative cervical kyphosis. We have received informed consent of this patient to submit this video.


Assuntos
Cifose , Lordose , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia , Humanos , Cifose/diagnóstico por imagem , Cifose/cirurgia , Lordose/cirurgia
20.
J Neurosurg Spine ; 34(3): 471-480, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33186902

RESUMO

OBJECTIVE: Potential advantages of using expandable versus static cages during transforaminal lumbar interbody fusion (TLIF) are not fully established. The authors aimed to compare the long-term radiographic outcomes of expandable versus static TLIF cages. METHODS: A retrospective review of 1- and 2-level TLIFs over a 10-year period with expandable and static cages was performed at the University of California, San Francisco. Patients with posterior column osteotomy (PCO) were subdivided. Fusion assessment, cage subsidence, anterior and posterior disc height, foraminal dimensions, pelvic incidence (PI), segmental lordosis (SL), lumbar lordosis (LL), pelvic incidence-lumbar lordosis mismatch (PI-LL), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA) were assessed. RESULTS: A consecutive series of 178 patients (with a total of 210 levels) who underwent TLIF using either static (148 levels) or expandable cages (62 levels) was reviewed. The mean patient age was 60.3 ± 11.5 years and 62.8 ± 14.1 years for the static and expandable cage groups, respectively. The mean follow-up was 42.9 ± 29.4 months for the static cage group and 27.6 ± 14.1 months for the expandable cage group. Within the 1-level TLIF group, the SL and PI-LL improved with statistical significance regardless of whether PCO was performed; however, the static group with PCOs also had statistically significant improvement in LL and SVA. The expandable cage with PCO subgroup had significant improvement in SL only. All of the foraminal parameters improved with statistical significance, regardless of the type of cages used; however, the expandable cage group had greater improvement in disc height restoration. The incidence of cage subsidence was higher in the expandable group (19.7% vs 5.4%, p = 0.0017). Within the expandable group, the unilateral facetectomy-only subgroup had a 5.6 times higher subsidence rate than the PCO subgroup (26.8% vs 4.8%, p = 0.04). Four expandable cages collapsed over time. CONCLUSIONS: Expandable TLIF cages may initially restore disc height better than static cages, but they also have higher rates of subsidence. Unilateral facetectomy alone may result in more subsidence with expandable cages than using bilateral PCO, potentially because of insufficient facet release. Although expandable cages may have more power to induce lordosis and restore disc height than static cages, subsidence and endplate violation may negate any significant gains compared to static cages.

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