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1.
Neurosurg Focus ; 55(3): E8, 2023 09.
Article in English | MEDLINE | ID: mdl-37657101

ABSTRACT

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common clinical degenerative disease treated with anterior cervical discectomy and fusion (ACDF), which seriously impacts quality of life and causes severe disability. The objective of the study was to determine the effect of different characteristics of the neurological deficit found in myelopathic patients undergoing ACDFs on hospital cost, length of stay (LOS), and discharge location. METHODS: This is a retrospective review of ACDF cases performed at a single institution by multiple surgeons from 2011 to 2017. Patient symptomatology, complications, comorbidities, demographics, surgical time, LOS, and discharge location were collected. Patients with readmissions or reoperations were excluded. Symptoms evaluated were based on clinical diagnosis, Japanese Orthopaedic Association classification, Ranawat grade, and Cooper scales. Symptoms were further grouped using principal component analysis. Cost was defined as surgical episode hospital stay costs plus outpatient clinic costs plus discharge disposition cost. Multivariate linear regression models were created to evaluate correlations with outcomes. The primary outcome was total 90-day hospital costs. Secondary outcomes were discharge location and LOS. RESULTS: A total of 250 patients were included in the analyses. Discharge location, neuromonitoring use, number of surgical vertebral levels, cage use, LOS, surgical time, having a complication, and sex were all found to be predictive of total 90-day costs. Myelopathic symptomatology was not found to be associated with increased 90-day costs (p ≥ 0.131) when correcting for these other factors. Lower-extremity functionality was found to be associated with increased LOS (p < 0.0001). Upper-extremity myelopathy was found to be associated with increased discharge location needs (p < 0.0001). CONCLUSIONS: Cervical myelopathy was not found to be predictive of total 90-day costs using symptomatology based on multiple myelopathy grading systems. Lower-extremity functionality was, however, found to predict LOS, while upper-extremity myelopathy was found to predict increased discharge location needs. This implies that preoperative deficits from myelopathy should not be considered in a bundled payment system; however, certain myelopathic symptoms should be considered when determining the cost of care.


Subject(s)
Hospital Costs , Patient Discharge , Humans , Length of Stay , Quality of Life , Diskectomy
2.
World Neurosurg ; 150: e621-e630, 2021 06.
Article in English | MEDLINE | ID: mdl-33757890

ABSTRACT

BACKGROUND: American Heart Association/American Stroke Association guidelines recommend endovascular stroke therapy (EST) with recombinant tissue plasminogen activator (rt-PA) for eligible patients in acute ischemic stroke (AIS). Using the National Inpatient Sample database, we evaluated trends in treatment with rt-PA and EST for AIS and their outcomes. METHODS: This is a cross-sectional observational study of patients with AIS admitted in US hospitals from 2012 to 2016. Patients were grouped into those who received rt-PA alone, EST alone, and rtPA+EST. Survey statistical procedures were performed. Multivariable regression analysis with pairwise comparisons of each treatment group with no treatment group was performed for discharge outcomes. RESULTS: The study included 2,290,520 patients with AIS with the mean age of 70.46 years. Treatment rates increased from 2012 to 2016 for rt-PA by 7% per year (5.86%-7.67%, odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.05-1.08) and EST by 38% per year (0.55%-1.75%, OR = 1.38, 95% CI: 1.31-1.45) but not rt-PA+EST (0.54%-0.57%, OR = 1.04, 95% CI: 0.99-1.08). The mean length of stay reduced from 2012 to 2016 for rt-PA (6.07-4.91 days, P < 0.0001) and rt-PA+EST (9.19-7.10 days, P = 0.0067) but not for EST (9.61-8.51 days, P = 0.5074). The odds of patients discharged home increased by 8%, 9%, and 15% among patients who received rt-PA alone, EST alone, and rt-PA+EST, respectively, compared with no treatment group. CONCLUSION: The utilization of rt-PA alone and EST alone increased but that of rt-PA+EST remained unchanged from 2012 to 2016 in the National Inpatient Sample.


Subject(s)
Endovascular Procedures/trends , Ischemic Stroke/therapy , Neurology/trends , Tissue Plasminogen Activator/therapeutic use , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Reperfusion/methods , United States
3.
Exp Neurol ; 333: 113429, 2020 11.
Article in English | MEDLINE | ID: mdl-32735873

ABSTRACT

Moderate acute intermittent hypoxia (AIH) elicits a persistent, serotonin-dependent increase in phrenic amplitude, known as phrenic long-term facilitation (pLTF). Although pLTF was originally demonstrated by carotid sinus nerve stimulation, AIH still elicits residual pLTF in carotid denervated (CBX) rats via a distinct, but unknown mechanism. We hypothesized that exaggerated hypoxia-induced hypotension after carotid denervation leads to greater spinal tissue hypoxia and extracellular adenosine accumulation, thereby triggering adenosine 2A receptor (A2A)-dependent pLTF. Phrenic activity, arterial pressure and spinal tissue oxygen pressure were measured in anesthetized CBX rats. Exaggerated hypoxia-induced hypotension after CBX was prevented via intravenous phenylephrine; without the hypotension, spinal tissue hypoxia during AIH was normalized, and residual pLTF was no longer observed. Spinal A2A (MSX-3), but not serotonin 2 receptor (5-HT2) inhibition (ketanserin), abolished residual pLTF in CBX rats. Thus, pLTF regulation may be altered in conditions impairing sympathetic activity and arterial pressure regulation, such as spinal cord injury.


Subject(s)
Carotid Body , Hypotension/etiology , Hypotension/metabolism , Hypoxia/complications , Long-Term Potentiation , Phrenic Nerve/physiopathology , Adenosine/metabolism , Animals , Arterial Pressure , Blood Gas Analysis , Denervation , Ketanserin/pharmacology , Long-Term Potentiation/drug effects , Male , Phenylephrine/pharmacology , Rats , Rats, Sprague-Dawley , Receptor, Adenosine A2A/metabolism , Serotonin 5-HT2 Receptor Antagonists/pharmacology , Spinal Cord/pathology
4.
J Vasc Surg ; 71(5): 1620-1628.e3, 2020 05.
Article in English | MEDLINE | ID: mdl-31611109

ABSTRACT

OBJECTIVE: To examine the regional variation and temporal change in lumen size along the entire autogenous vein bypass graft used for treating arterial occlusive disease in lower extremity and to explore the factors associated with graft expansive or constrictive remodeling. METHODS: Patients were prospectively scanned using contrast-enhanced computed tomography at 1 week and 1, 6, and 12 months postoperatively to obtain lumen cross-sectional areas at 1-mm intervals along the entire grafts. Graft lumen remodeling characteristics and the associated demographic and clinical factors were examined. RESULTS: Fifty-six patients with at least two consecutive computed tomography scans were analyzed. Patients with a composite or longer graft, or with diabetes, had a larger lumen cross-sectional area variation along the graft. The mean lumen cross-sectional areas of all the grafts demonstrated no significant changes through 12 months. However, individually, graft remodeling was time dependent and there was a more dramatic change in lumen cross-sectional area within the first postoperative month. At 12 months, a near equal distribution between expansive and constrictive grafts existed. A negative relation between the initial lumen diameters and the subsequent lumen diameter changes was observed. Eleven grafts failed within 12 months; failed and patent grafts had similar mean lumen cross-sectional areas at all four time points, but failed grafts had a larger maximal local cross-sectional area reduction from 1 week to 1 month (58.0 ± 6.7% vs 38.1 ± 3.1%, mean ± standard error of the mean, failed vs patent, P = .004). Black patients had a smaller mean lumen cross-sectional area than white patients at all four time points and also had a higher early percent mean area reduction (-20.5 ± 6.3% vs -1.0 ± 3.7%, black vs white, P = .018). Cilostazol use was associated with early expansive graft remodeling. CONCLUSIONS: Vein grafts remodel heterogeneously and dynamically. Remodeling is associated with initial graft lumen size, race, and cilostazol use. It is found that remodeling that produces some critical minimum area or maximal percent reduction during the first postoperative month may predispose to vein graft failure. These findings offer insight into further investigation to examine the underlying mechanisms and opportunities to improve graft remodeling and durability.


Subject(s)
Lower Extremity/blood supply , Peripheral Arterial Disease/surgery , Vascular Grafting , Vascular Remodeling , Veins/transplantation , Aged , Cardiovascular Agents/therapeutic use , Cilostazol/therapeutic use , Computed Tomography Angiography , Female , Humans , Longitudinal Studies , Male , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/physiopathology , Phlebography , Prospective Studies , Time Factors , Treatment Outcome , Vascular Grafting/adverse effects , Veins/diagnostic imaging , Veins/physiopathology
5.
World Neurosurg ; 135: e510-e519, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31863896

ABSTRACT

BACKGROUND: Patient safety indicators (PSIs) and hospital-acquired conditions (HACs) are reported quality measures. We compared their prevalence in patients with secretory and nonsecretory pituitary adenoma using the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. METHODS: The NIS was queried for hospitalizations 2002-2014 involving pituitary adenomas. Prevalence of PSI, HAC, and 9 pituitary-related complications was determined using International Classification of Diseases, Ninth Revision codes. Patient risk factors were evaluated through multivariate analysis. RESULTS: A total of 20,743 patients with nonsecretory tumor and 3385 patients with secretory tumor were identified. Among patients with nonsecretory tumor, 3.79% experienced any PSI or HAC. Of patients with secretory tumor, 2.54% had any PSI or HAC. Before adjusting for covariation, secretory patients were less likely to have any PSI or HAC (odds ratio [OR], 0.652; P = 0.0002), experience any pituitary-related complication (OR, 0.804; P < 0.0001), have a poor outcome (hazard ratio [HR], 0.435; P < 0.0001), and die during hospitalization (HR, 0.293; P = 0.0015). Secretory patients had significantly shorter mean hospital length of stay (secretory/nonsecretory percent difference, -11.95%; P < 0.0001). However, inverse propensity score-weighted ORs comparing the groups' outcomes showed that there was no significant difference in the prevalence of any PSIs and HACs (OR, 0.963; P = 0.8570), pituitary-related complications (OR, 0.894; P = 0.1321), poor outcomes (HR, 0.990; P = 0.9287), in-hospital death (HR, 0.663; P = 0.2967), and length of stay (percent difference, -2.31%; P = 0.2967) between groups. CONCLUSIONS: Lack of significant difference in outcome measures after controlling for covariation is consistent with our finding that patients with nonsecretory tumor have more comorbidities on presentation for treatment. PSIs and HACs have limited ability to measure complications specific to pituitary tumors.


Subject(s)
Adenoma/complications , Pituitary Neoplasms/complications , Adult , Female , Hospitalization , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors
6.
J Neurosurg ; 132(3): 818-824, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30771769

ABSTRACT

OBJECTIVE: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online surgical risk calculator uses inherent patient characteristics to provide predictive risk scores for adverse postoperative events. The purpose of this study was to determine if predicted perioperative risk scores correlate with actual hospital costs. METHODS: A single-center retrospective review of 1005 neurosurgical patients treated between September 1, 2011, and December 31, 2014, was performed. Individual patient characteristics were entered into the NSQIP calculator. Predicted risk scores were compared with actual in-hospital costs obtained from a billing database. Correlational statistics were used to determine if patients with higher risk scores were associated with increased in-hospital costs. RESULTS: The Pearson correlation coefficient (R) was used to assess the correlation between 11 types of predicted complication risk scores and 5 types of encounter costs from 1005 health encounters involving neurosurgical procedures. Risk scores in categories such as any complication, serious complication, pneumonia, cardiac complication, surgical site infection, urinary tract infection, venous thromboembolism, renal failure, return to operating room, death, and discharge to nursing home or rehabilitation facility were obtained. Patients with higher predicted risk scores in all measures except surgical site infection were found to have a statistically significant association with increased actual in-hospital costs (p < 0.0005). CONCLUSIONS: Previous work has demonstrated that the ACS NSQIP surgical risk calculator can accurately predict mortality after neurosurgery but is poorly predictive of other potential adverse events and clinical outcomes. However, this study demonstrates that predicted high-risk patients identified by the ACS NSQIP surgical risk calculator have a statistically significant moderate correlation to increased actual in-hospital costs. The NSQIP calculator may not accurately predict the occurrence of surgical complications (as demonstrated previously), but future iterations of the ACS universal risk calculator may be effective in predicting actual in-hospital costs, which could be advantageous in the current value-based healthcare environment.

7.
Front Mol Neurosci ; 11: 82, 2018.
Article in English | MEDLINE | ID: mdl-29643764

ABSTRACT

Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas. Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed. Results: The results demonstrate that when compared with IDH1-mutant tumors, IDH1 wildtype tumors represent an immunosuppression landscape and elevated levels of PD-L1 expression. DNA hypo-methylation of the PD-L1 gene, as well as high gene and protein expressions, were observed in the wildtype tumors. We also found that quantitative levels of IDH1 mutant proteins were positively associated with recurrence-free survival (RFS). A key product of the IDH1 mutation (2-hydroxyglutarate) was found to transiently increase DNA methylation and suppress PD-L1 expression. Conclusions: IDH1 mutations impact the immune landscape of gliomas by affecting immune infiltrations and manipulating checkpoint ligand PD-L1 expression. Applications of immune checkpoint inhibitors may be beneficial for chemoradiation-insensitive IDH1-wildtype gliomas.

8.
Oper Neurosurg (Hagerstown) ; 14(3): 224-230, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29462447

ABSTRACT

BACKGROUND: Spontaneous thoracic ankylosis is a progressive degenerative process that predisposes patients to potentially highly unstable traumatic injuries. Acute hyperextension fractures result in dynamic instability putting the spinal cord at risk. OBJECTIVE: To describe preoperative radiographic characteristics of fractures of the ankylotic thoracic spine and relate findings to early postoperative radiographic and clinical outcomes. METHODS: A single center, retrospective review was performed of 28 surgically treated patients with fractures of the ankylotic thoracic spine. Radiographic assessment included preoperative fracture angulation (FA) and fracture displacement (FD), and postoperative change in sagittal alignment. Early clinical outcomes included preoperative and postoperative American Spinal Injury Association (ASIA) grade and perioperative complications. RESULTS: Seven patients (25%) presented with poor neurological grade (ASIA A-C) compared to 21 (75%) with good grade (ASIA D, E). At presentation, poor grade patients had a mean FA of 16.4° (range 0°-34.5°), and FD of 7.76 mm (range 0.8-9.2). Good grade patients had a mean FA of 18.2° (range 0°-43.3°), and FD of 4.77 mm (range 0-25.1). There was no statistically significant difference in FA or FD between groups (P = .70 and .20 respectively). All underwent posterior pedicle screw fixation for stabilization. Fifty per cent of patients presenting with ASIA C or D spinal cord injury improved 1 or more ASIA grades. There were no perioperative complications. Early postoperative sagittal alignment was maintained with a mean change of -2.6°. CONCLUSION: Presenting fracture alignment does not significantly correlate with pre- or postoperative neurological status. Early posterior stabilization preserved neurological function, with neurological recovery occurring in a portion of individuals.


Subject(s)
Ankylosis/surgery , Spinal Fractures/surgery , Spinal Fusion/methods , Thoracic Vertebrae/surgery , Aged , Aged, 80 and over , Ankylosis/diagnostic imaging , Female , Humans , Male , Middle Aged , Pedicle Screws , Postoperative Period , Retrospective Studies , Spinal Fractures/diagnostic imaging , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/injuries , Treatment Outcome
9.
J Neurosurg ; 130(1): 273-277, 2018 01 26.
Article in English | MEDLINE | ID: mdl-29372882

ABSTRACT

OBJECTIVE: Comorbidities have a significant effect on patient outcomes. Accounting for this effect is especially important in retrospective reviews of large databases; overpowered studies are at risk for finding significant results because of inaccurate patient risk stratification. The authors previously created a neurovascular comorbidities index (NCI) for patients with an unruptured intracranial aneurysm and found that the model's ability to predict patient outcomes was statistically significantly improved over that of the routinely used Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). In this study, the authors aimed to validate use of the NCI over that of the CCI and ECI for risk stratification of patients with other neurovascular diseases. METHODS: The authors queried the National (Nationwide) Inpatient Sample database for the years 2002-2012 to compare the accuracy of the previously validated NCI with that of the CCI and ECI with respect to predicting outcomes for patients who had an arteriovenous malformation, a ruptured intracranial aneurysm, carotid artery stenosis, or dural arteriovenous fistula and who underwent surgical intervention. RESULTS: For patients with an arteriovenous malformation, the NCI outperformed the CCI and ECI in predicting poor outcome, hospital length of stay (LOS), and total cost but was equivalent to the CCI in predicting death. For patients with a ruptured intracranial aneurysm, the NCI outperformed the ECI and CCI in predicting death, poor outcome, LOS, and total cost. For patients with carotid artery stenosis, the NCI outperformed the ECI and CCI in predicting LOS, but it was equivalent to the ECI in predicting death and total cost and inferior to the CCI in predicting poor outcome (p < 0.002 for all). An insufficient number of patients with dural arteriovenous fistula who underwent surgical intervention were available for analysis (n < 10), and they therefore were excluded from study. For 11 of 12 metrics, the NCI was the significantly more efficient model. CONCLUSIONS: The NCI outperforms the CCI and ECI by providing more appropriate and efficient risk stratification of patients regarding death, outcome, LOS, and cost. Given this finding, the NCI should be used for retrospective reviews of patient outcomes instead of the CCI or ECI.


Subject(s)
Aneurysm, Ruptured/epidemiology , Arteriovenous Fistula/epidemiology , Carotid Stenosis/epidemiology , Intracranial Aneurysm/epidemiology , Adult , Aged , Aneurysm, Ruptured/complications , Arteriovenous Fistula/complications , Carotid Stenosis/complications , Comorbidity , Databases, Factual , Female , Hospitalization/statistics & numerical data , Humans , Intracranial Aneurysm/complications , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , United States
10.
Neuro Oncol ; 20(1): 55-65, 2018 01 10.
Article in English | MEDLINE | ID: mdl-28651374

ABSTRACT

Background: Cancer immunotherapy represents a promising treatment approach for malignant gliomas but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified cluster of differentiation (CD)70 as a novel immunosuppressive ligand and glioma target. Methods: Normal tissues derived from 52 different organs and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression. The association between CD70 and patients' overall survival and its impact on T-cell death was also evaluated. Human and mouse CD70-specific chimeric antigen receptors (CARs) were tested respectively against human primary GBMs and murine glioma lines. The antitumor efficacies of these CARs were also examined in orthotopic xenograft and syngeneic models. Results: CD70 was not detected in peripheral and brain normal tissues but was constitutively overexpressed by isocitrate dehydrogenase (IDH) wild-type primary LGGs and GBMs in the mesenchymal subgroup and recurrent tumors. CD70 was also associated with poor survival in these subgroups, which may link to its direct involvement in glioma chemokine productions and selective induction of CD8+ T-cell death. To explore the potential for therapeutic targeting of this newly identified immunosuppressive axis in GBM tumors, we demonstrate that both human and mouse CD70-specific CAR T cells recognize primary CD70+ GBM tumors in vitro and mediate the regression of established GBM in xenograft and syngeneic models without illicit effect. Conclusion: These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.


Subject(s)
Brain Neoplasms/therapy , CD27 Ligand/immunology , Receptors, Chimeric Antigen/immunology , Animals , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cell Line, Tumor , Glioma , Humans , Immunotherapy, Adoptive/methods , Isocitrate Dehydrogenase/genetics , Mice , T-Lymphocytes/immunology , Tumor Microenvironment/immunology
11.
Front Immunol ; 8: 1451, 2017.
Article in English | MEDLINE | ID: mdl-29163521

ABSTRACT

BACKGROUND: Angiogenesis and immune cell infiltration are key features of gliomas and their manipulation of the microenvironment, but their prognostic significance remains indeterminate. We evaluate the interconnection between tumor-infiltrating lymphocyte (TIL) and tumor blood-vasculatures in the context of glioma progression. METHODS: Paired tumor tissues of 44 patients from three tumor-recurrent groups: diffuse astrocytomas (DA) recurred as DA, DA recurred as glioblastomas (GBM), and GBM recurred as GBM were evaluated by genetic analysis, immunohistochemistry for tumor blood vessel density, TIL subsets, and clinical outcomes. These cells were geographically divided into perivascular and intratumoral TILs. Associations were examined between these TILs, CD34+ tumor blood vessels, and clinical outcomes. To determine key changes in TIL subsets, microarray data of 15-paired tumors from patients who failed antiangiogenic therapy- bevacizumab, and 16-paired tumors from chemo-naïve recurrent GBM were also evaluated and compared. RESULTS: Upon recurrence in primary gliomas, similar kinetic changes were found between tumor blood vessels and each TIL subset in all groups, but only CD4+ including Foxp3+ TILs, positively correlated with the density of tumor blood vessels. CD4 was the predominant T cell population based on the expression of gene-transcripts in primary GBMs, and increased activated CD4+ T cells were revealed in Bevacizumab-resistant recurrent tumors (not in chemo-naïve recurrent tumors). Among these TILs, 2/3 of them were found in the perivascular niche; Foxp3+ T cells in these niches not only correlated with the tumor vessels but were also an independent predictor of shortened recurrence-free survival (RFS) (HR = 4.199, 95% CI 1.522-11.584, p = 0.006). CONCLUSION: The minimal intratumoral T cell infiltration and low detection of CD8 transcripts expression in primary GBMs can potentially limit antitumor response. CD4+ and perivascular Foxp3+ TILs associate with tumor angiogenesis and tumor progression in glioma patients. Our results suggest that combining antiangiogenic agents with immunotherapeutic approaches may help improve the antitumor efficacy for patients with malignant gliomas.

12.
Kidney Int Rep ; 2(3): 332-341, 2017 May.
Article in English | MEDLINE | ID: mdl-28845469

ABSTRACT

INTRODUCTION: Contemporary dogma has classically attributed hand dysfunction following hemodialysis arteriovenous fistula (AVF) placement to regional ischemia. We hypothesize that hemodynamic perturbations alone do not entirely explain the postoperative changes in hand function and, furthermore, that various elements of hand function are differentially affected following surgery. METHODS: Bilateral wrist and digital pressures and upper extremity nerve conduction tests were recorded preoperatively and at 6 weeks and 6 months following upper extremity AVF construction in 46 patients. Concurrently, biomechanical tests were administered to evaluate multiple limb functional domains including grip strength, dexterity, sensation and perception of hand function. RESULTS: Mean age was 59±14 years (75% male) and 48% were on hemodialysis at the time of access placement. 69% had a brachial-based AVF, and the remainder had radial-based accesses. Six weeks following AVF placement, a significant decrease in access side digital pressures was observed, with only partial recovery at 6 months (P<0.0001). Grip strength was significantly worse in the access side limb (P=0.0003), and Disability of Arm, Shoulder and Hand Questionnaire (DASH) score substantially worsened postoperatively (P=0.06). Digital sensation and limb dexterity did not differ between limb sides (P>0.1) or change significantly over time (P>0.1). Principal component analyses demonstrated that nerve conduction parameters tended to track the biomechanical parameters, yet both were relatively independent of the hemodynamic parameters. CONCLUSION: Our findings suggest that ischemia alone does not completely explain access-related hand dysfunction and that future study is needed to elucidate alternative mechanisms.

13.
Int J Cancer ; 141(7): 1434-1444, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28612394

ABSTRACT

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM.


Subject(s)
Brain Neoplasms/metabolism , Brain Neoplasms/pathology , CD27 Ligand/metabolism , Glioblastoma/metabolism , Glioblastoma/secondary , Immune Tolerance , Antigens, CD/analysis , Antigens, CD/genetics , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/analysis , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, Differentiation, Myelomonocytic/metabolism , Brain/cytology , Brain Neoplasms/immunology , CD27 Ligand/analysis , CD27 Ligand/genetics , Cell Line, Tumor , Cell Migration Assays, Macrophage/methods , Cell Movement , Gene Expression Regulation, Neoplastic , Glioblastoma/immunology , Glioblastoma/mortality , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Immunity, Cellular , Macrophages/chemistry , Macrophages/cytology , Macrophages/immunology , Neoplasm Metastasis , Receptors, Cell Surface/analysis , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Tumor Microenvironment/immunology
14.
J Neurosurg ; 127(1): 123-131, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27689459

ABSTRACT

OBJECTIVE An increased extent of resection (EOR) has been shown to improve overall survival of patients with glioblastoma (GBM) but has the potential for causing a new postoperative neurological deficit. To investigate the impact of surgical neurological morbidity on survival, the authors performed a retrospective analysis of the clinical data from patients with GBM to quantify the impact of a new neurological deficit on the survival benefit achieved with an increased EOR. METHODS The data from all GBM patients who underwent resection at the University of Florida from 2010 to 2015 with postoperative imaging within 72 hours of surgery were included in the study. Retrospective analysis was performed on clinical outcomes and tumor volumes determined on postoperative and follow-up imaging examinations. RESULTS Overall, 115 patients met the inclusion criteria for the study. Tumor volume at the time of presentation was a median of 59 cm3 (enhanced on T1-weighted MRI scans). The mean EOR (± SD) was 94.2% ± 8.7% (range 59.9%-100%). Almost 30% of patients had a new postoperative neurological deficit, including motor weakness, sensory deficits, language difficulty, visual deficits, confusion, and ataxia. The neurological deficits had resolved in 41% of these patients on subsequent follow-up examinations. The median overall survival was 13.1 months (95% CI 10.9-15.2 months). Using a multipredictor Cox model, the authors observed that increased EOR was associated with improved survival except for patients with smaller tumor volumes (≤ 15 cm3). A residual volume of 2.5 cm3 or less predicted a favorable overall survival. Developing a postoperative neurological deficit significantly affected survival (9.2 months compared with 14.7 months, p = 0.02), even if the neurological deficit had resolved by the first follow-up. However, there was a trend of improved survival among patients with resolution of a neurological deficit by the first follow-up compared with patients with a permanent neurological deficit. Any survival benefit from achieving a 95% EOR was abrogated by the development of a new neurological deficit postoperatively. CONCLUSIONS Developing a new neurological deficit after resection of GBM is associated with a decrease in overall survival. A careful balance between EOR and neurological compromise needs to be taken into account to reduce the likelihood of neurological morbidity from surgery.


Subject(s)
Brain Neoplasms/mortality , Brain Neoplasms/surgery , Glioblastoma/mortality , Glioblastoma/surgery , Nervous System Diseases/mortality , Postoperative Complications/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Young Adult
15.
Transpl Int ; 17(4): 195-201, 2004 May.
Article in English | MEDLINE | ID: mdl-15064924

ABSTRACT

The ability to predict renal allograft dysfunction in the short term and predict graft survival by quantifying the macrophage infiltrate in allograft renal biopsies is described. Renal allograft biopsies performed for cause in 41 consecutive patients were scored for macrophages (macrophage index, MI) by use of a modified Banff score of inflammation (BSI), and the impact of the MI on serum creatinine (SCr) levels 3 months post-biopsy (post-Bx) and on graft survival was quantified. Biopsies were stained for macrophages, individual lesions semiquantified and MI, BSI and chronic allograft damage index (CADI) obtained. The effects of pathologic indices on 3 month post-Bx SCr and graft survival were quantified by multivariate analysis and Cox regression. Glomerular and interstitial macrophage scores correlated inversely with graft survival. MI predicted an increase in SCr 3 months post-Bx (P=0.02). MI >3 (hazard ratio 23.13, P=0.003) also had a powerful negative predictive value on graft survival.


Subject(s)
Graft Rejection/diagnosis , Graft Survival , Kidney Transplantation , Kidney/pathology , Kidney/physiopathology , Macrophages/metabolism , Biomarkers , Biopsy, Needle , Creatine/blood , Female , Graft Rejection/blood , Humans , Male , Predictive Value of Tests , Time Factors , Transplantation, Homologous
16.
Can Vet J ; 43(7): 528-34, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12125184

ABSTRACT

The objective of this study was to determine the complication rate and evaluate factors affecting the outcome of olecranon osteotomy in dogs. Medical records were searched to identify dogs that had undergone olecranon osteotomy (stabilized with 2 Kirschner wires and a figure-of-8 wire) during internal fixation of a supracondylar or condylar humeral fracture. Signalment, description of the fracture, parameters regarding the osteotomy and its repair, and radiographic outcome were recorded. A logistic regression model compared patient and technical parameters with the osteotomy outcome. Of the 19 dogs, 7 (37%) had complications of the osteotomy, including osteomyelitis, loss of reduction, and improper placement and migration of the Kirschner wires. Olecranon osteotomy is associated with a high complication rate in dogs; however, there was no correlation between patient-related or technical parameters and the development of complications. Further clinical and biomechanical investigations are warranted to improve the results of olecranon osteotomy and its repair.


Subject(s)
Dogs/surgery , Fracture Fixation, Internal/veterinary , Humeral Fractures/veterinary , Osteotomy/veterinary , Ulna/surgery , Animals , Bone Plates/veterinary , Bone Screws/veterinary , Bone Wires/veterinary , Dogs/injuries , Female , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Humeral Fractures/surgery , Incidence , Male , Osteomyelitis/etiology , Osteomyelitis/veterinary , Osteotomy/adverse effects , Osteotomy/instrumentation , Osteotomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/veterinary , Retrospective Studies , Risk Factors , Treatment Outcome
17.
Am J Vet Res ; 63(1): 143-7, 2002 Jan.
Article in English | MEDLINE | ID: mdl-16206796

ABSTRACT

OBJECTIVE: To determine regional and zonal variation in sulfation patterns of chondroitin sulfate in normal equine corneal stroma. SAMPLE POPULATION: 22 normal eyes from 11 horses. PROCEDURE: Corneas were collected within 24 hours of death from equine necropsy specimens. After papain-chondroitinase digestion of corneal tissue, disaccharides deltaDi4S and deltaDi6S were quantified by use of capillary zone electrophoresis in the superficial, middle, and deep zones of central and peripheral regions of the cornea. RESULTS: For the 2 regions combined, deltaDi6S/deltaDi4S values were significantly lower in the deep and middle zones, compared with that of the superficial zone. In the central region, deep and middle zones had significantly lower deltaDi6S/deltaDi4S values than the superficial zone did. In the peripheral region, the deep zone had significantly lower deltaDi6S/deltaDi4S values, compared with superficial and middle zones. In the deep zone, the peripheral region had significantly lower deltaDi6S/deltaDi4S values than the central region did. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of deltaDi6S/deltaDi4S values follows a gradient across the healthy equine cornea, being smallest in the deep and middle zones of the central region and the deep zone of the peripheral region. Regional and zonal differences in the distribution of stromal deltaDi6S and deltaDi4S may influence the role of glycosaminoglycans in health, disease, and wound repair of the equine cornea.


Subject(s)
Chondroitin Sulfates/chemistry , Corneal Stroma/chemistry , Horses/metabolism , Animals , Reference Values
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