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2.
PLoS One ; 18(10): e0293121, 2023.
Article in English | MEDLINE | ID: mdl-37878597

ABSTRACT

BACKGROUND: Women are less likely to receive left ventricular assist devices and are more likely to experience poor outcomes. However, how gender impacts LVAD decision-making regarding LVAD implantation and the effects of that decision remains unknown. METHODS: We performed a sub-group analysis from the stepped-wedge DECIDE-LVAD trial, which tested a decision-support intervention for patients considering LVAD therapy. RESULTS: Excluding 9 patients who withdrew from assessments, of the 239 patients analyzed, 203 (85%) were men and 36 (15%) were women. More men received LVADs (70%) than women (61%) and more men were alive at 6 months compared to women, both among those who received LVADs (87% vs 82%) and those who did not (74% vs 50%) (p = 0.002). Compared to men, women were more likely to have decision regret, depressive symptoms and perceived stress at baseline but not at follow-up. At 6-month follow-up, men experience improvements in decisional conflict, acceptance of illness, struggle with illness, and perceived stress-none of those improvements were noted amongst women. Compared to men who received LVADs, women receiving LVADs had worse decision regret and depressive symptoms at baseline and worse acceptance of illness and perceived stress at six months. Men who received LVADs experienced improvement in decisional conflict and perceived stress, while women did not experience these improvements. Both men and women who received LVADs experienced improvement in depressive symptoms. Quality of life as assessed by EuroQol visual analog scale improved for both men and women who received LVADs but not for those who did not receive LVADs; no gender differences in quality of life were noted. CONCLUSION: Women require greater decisional support at time of decision to undergo LVAD implantation and subsequently might benefit from more intensive psychosocial support.


Subject(s)
Heart Failure , Heart-Assist Devices , Male , Humans , Female , Quality of Life , Heart-Assist Devices/adverse effects , Emotions , Decision Making
3.
JAMA Netw Open ; 6(4): e239638, 2023 04 03.
Article in English | MEDLINE | ID: mdl-37093601

ABSTRACT

Importance: The underuse of oral anticoagulation in patients with nonvalvular atrial fibrillation (AF) is a major issue that is not well understood. Objective: To understand the lack of anticoagulation by assessing the perceptions of patients with AF who are not receiving anticoagulation and their physician's about the risk of stroke and the benefits and risks of anticoagulation. Design, Setting, and Participants: This cohort study included patients with nonvalvular AF and a CHA2DS2-VASc score of 2 or more (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) who were not receiving anticoagulation and were enrolled from 19 sites within the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence Registry (PINNACLE Registry) between January 18, 2017, and May 7, 2018. Data were collected from January 18, 2017, to September 30, 2019, and analyzed from April 2022 to March 2023. Exposure: Each patient enrolled in the study completed a survey, and their treating physician then conducted a clinical review of their care. Main Outcomes and Measures: Assessment of willingness for anticoagulation treatment and its appropriateness after central review by a panel of 4 cardiologists. Use of anticoagulation at 1 year follow-up was compared vs similar patients at other centers in the PINNACLE Registry. Results: Of the 817 patients enrolled, the median (IQR) age was 76.0 (69.0-83.0) years, 369 (45.2%) were women, and the median (IQR) CHA2DS2-VASc score was 4.0 (3.0-6.0). The top 5 reasons physicians cited for no anticoagulation were low AF burden or successful rhythm control (278 [34.0%]), patient refusal (272 [33.3%]), perceived low risk of stroke (206 [25.2%]), fall risk (175 [21.4%]), and high bleeding risk (167 [20.4%]). After rereview, 221 physicians (27.1%) would reconsider prescribing oral anticoagulation as compared with 311 patients (38.1%), including 67 (24.6%) whose physician cited patient refusal. Of 647 patients (79.2%) adjudicated as appropriate or may be appropriate for anticoagulation, physicians would reconsider anticoagulation for only 177 patients (21.2%), while 527 patients (64.5%) would either agree to starting anticoagulation (311 [38.1%]) or were neutral (216 [27.3%]) to starting anticoagulation. Upon follow-up, 119 patients (14.6%) in the BOAT-AF study were prescribed anticoagulation, as compared with 55 879 of 387 975 similar patients (14.4%) at other centers in the PINNACLE Registry. Conclusions and Relevance: The findings of this cohort study suggest that patients with AF who are not receiving anticoagulation are more willing to consider anticoagulation than their physicians. These data emphasize the need to revisit any prior decision against anticoagulation in a shared decision-making manner.


Subject(s)
Anticoagulants , Atrial Fibrillation , Humans , Male , Female , Aged , Atrial Fibrillation/drug therapy , Anticoagulants/therapeutic use , Cohort Studies , Aged, 80 and over , Treatment Outcome
4.
JAMA Cardiol ; 8(5): 510, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37018008

ABSTRACT

This case report discusses a diagnosis of extracardiac shunt in a woman aged 65 years with giant right atrium and recurrent heart failure exacerbations.


Subject(s)
Dyspnea , Echocardiography , Female , Humans , Aged , Dyspnea/etiology
6.
Eur Heart J Acute Cardiovasc Care ; 11(5): 442-449, 2022 Jun 14.
Article in English | MEDLINE | ID: mdl-35363258

ABSTRACT

The modern cardiac intensive care unit (CICU) specializes in the care of a broad range of critically ill patients with both cardiac and non-cardiac serious illnesses. Despite advances, most conditions that necessitate CICU admission such as cardiogenic shock, continue to have a high burden of morbidity and mortality. The CICU often serves as the final destination for patients with end-stage disease, with one study reporting that one in five patients in the USA die in an intensive care unit (ICU) or shortly after an ICU admission. Palliative care is a broad subspecialty of medicine with an interdisciplinary approach that focuses on optimizing patient and family quality of life (QoL), decision-making, and experience. Palliative care has been shown to improve the QoL and symptom burden in patients at various stages of illness, however, the integration of palliative care in the CICU has not been well-studied. In this review, we outline the fundamental principles of high-quality palliative care in the ICU, focused on timeliness, goal-concordant decision-making, and family-centred care. We differentiate between primary palliative care, which is delivered by the primary CICU team, and secondary palliative care, which is provided by the consulting palliative care team, and delineate their responsibilities and domains. We propose clinical triggers that might spur serious illness communication and reappraisal of patient preferences. More research is needed to test different models that integrate palliative care in the modern CICU.


Subject(s)
Palliative Care , Quality of Life , Critical Illness , Hospitalization , Humans , Intensive Care Units
7.
Telemed J E Health ; 28(6): 838-846, 2022 06.
Article in English | MEDLINE | ID: mdl-34726542

ABSTRACT

Objective:To compare clinical recommendations given by psychiatrists and the adherence to these recommendations by primary care physicians (PCP) following consultations conducted by asynchronous telepsychiatry (ATP) and synchronous telepsychiatry (STP).Materials and Methods:ATP and STP consultations were compared using intermediate data from a randomized clinical trial with adult participant enrollment between April 2014 and December 2017. In both study arms, PCPs received written recommendations from the psychiatrist after each encounter. Independent clinicians reviewed PCP documentation to measure adherence to those recommendations in the 6 months following the baseline consultation.Results:Medical records were reviewed for 645 psychiatrists' consult recommendations; 344 from 61 ATP consultations and 301 from 62 STP consultations. Of those recommendations, 191 (56%) and 173 (58%) were rated fully adherent by two independent raters for ATP and STP, respectively. In a multilevel ordinal logistic regression model adjusted for recommendation type and recommended implementation timing, there was no statistically significant difference in adherence to recommendations for ATP compared with STP (adjusted odds ratio = 0.91, 95% confidence interval = 0.51-1.62). The profiles of recommendation type were comparable between ATP and STP.Conclusions:This is the first PCP adherence study comparing two forms of telemedicine. Although we did not find evidence of a difference between ATP and STP; this study supports the feasibility and acceptability of ATP and STP for the provision of collaborative psychiatric care. Clinical Trial Identifier NCT02084979.


Subject(s)
Physicians, Primary Care , Psychiatry , Telemedicine , Adenosine Triphosphate , Adult , Humans , Referral and Consultation
8.
Clin Cardiol ; 44(7): 1002-1010, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34042199

ABSTRACT

BACKGROUND: The RE-DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y12 inhibitor, either clopidogrel or ticagrelor, reduced the risk of bleeding without an increased risk of thromboembolic events as compared to triple therapy with warfarin in addition to a P2Y12 inhibitor and aspirin. What remains unclear is whether this effect is consistent between males and females undergoing PCI. HYPOTHESIS: The reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y12 inhibitor in comparison to triple therapy with warfarin, a P2Y12 inhibitor and aspirin is consistent in females and males. METHODS: The primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non-major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint. RESULTS: A total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47-1.01, males: HR 0.46, 95% CI 0.37-0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively). CONCLUSIONS: Consistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex.


Subject(s)
Atrial Fibrillation , Coronary Artery Disease , Percutaneous Coronary Intervention , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Coronary Artery Disease/drug therapy , Dabigatran/adverse effects , Drug Therapy, Combination , Female , Fibrinolytic Agents/adverse effects , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Warfarin/adverse effects
10.
Neuro Oncol ; 21(8): 1060-1068, 2019 08 05.
Article in English | MEDLINE | ID: mdl-30796838

ABSTRACT

BACKGROUND: The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest. METHODS: Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS). RESULTS: One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: -100 vs -57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (-45%) compared with ICI naive lesions (-63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (-100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3-5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002). CONCLUSIONS: Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.


Subject(s)
Brain Neoplasms , Radiosurgery , B7-H1 Antigen/antagonists & inhibitors , Brain Neoplasms/therapy , Humans , Immune Checkpoint Inhibitors , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Retrospective Studies
11.
Neuro Oncol ; 21(5): 659-668, 2019 05 06.
Article in English | MEDLINE | ID: mdl-30726965

ABSTRACT

BACKGROUND: Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates. METHODS: Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib. Outcome variables included the proportion of patients who achieved an intracranial complete response or progressive disease according to the RECIST 1.1 criteria, as well as individual lesion response rates, distant intracranial failure, and radiation necrosis. RESULTS: Eighty-four patients with 487 brain metastases met inclusion criteria during the study period. Over 138 treatment sessions, 132 lesions (27%) were treated with SRS and concurrent lapatinib, while 355 (73%) were treated with SRS without lapatinib. Compared with patients treated with SRS alone, patients treated with concurrent lapatinib had higher rates of complete response (35% vs 11%, P = 0.008). On a per-lesion basis, best objective response was superior in the concurrent lapatinib group (median 100% vs 70% reduction, P < 0.001). Concurrent lapatinib was not associated with an increased risk of grade 2+ radiation necrosis (1.0% with concurrent lapatinib vs 3.5% without, P = 0.27). Lapatinib had no protective effect on distant intracranial failure rates (48% vs 49%, P = 0.91). CONCLUSION: The addition of concurrent lapatinib to SRS was associated with improved complete response rates among patients with HER2-positive brain metastases.


Subject(s)
Antineoplastic Agents/therapeutic use , Brain Neoplasms/therapy , Breast Neoplasms/therapy , Lapatinib/therapeutic use , Radiosurgery/mortality , Receptor, ErbB-2/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Brain Neoplasms/secondary , Breast Neoplasms/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
12.
J Neurooncol ; 133(2): 357-368, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28434110

ABSTRACT

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.


Subject(s)
Brain Neoplasms/drug therapy , Brain/pathology , Cranial Irradiation/adverse effects , Necrosis/etiology , Radiation Injuries/etiology , Radiosurgery/adverse effects , Aged , Brain Neoplasms/mortality , Cohort Studies , Female , Humans , Karnofsky Performance Status , Male , Middle Aged , Proportional Hazards Models , Radiation Injuries/mortality , Risk Factors
13.
J Clin Neurosci ; 21(12): 2096-101, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25037313

ABSTRACT

Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the meta-analysis. Patients presented at a mean of 8.2months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p<0.001) and OS (p=0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p=0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.


Subject(s)
Brain Neoplasms/physiopathology , Brain Neoplasms/surgery , Ependymoma/physiopathology , Ependymoma/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/pathology , Disease-Free Survival , Ependymoma/pathology , Female , Humans , Male , Meta-Analysis as Topic , Middle Aged , Prognosis , Proportional Hazards Models , Supratentorial Neoplasms/surgery , Young Adult
14.
Neurosurg Rev ; 37(2): 179-92; discussion 192, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24068529

ABSTRACT

Choroid plexus carcinoma (CPC) is a World Health Organization (WHO) grade III brain tumor with a poor prognosis that occurs mainly in children. Gross total resection of CPC is highly recommended and is associated with improved overall survival, although it is often associated with increased morbidity. The use of adjuvant therapies has yet to be standardized, although evidence suggests that for patients with incompletely resected CPCs, a combination of chemotherapy and radiation therapy may be beneficial. The use of radiation therapy for younger children (<3 years old) with CPC, however, is not recommended, due to the potential negative neurological sequelae associated with radiation to the developing brain. Given that the majority of CPC patients are young children, questions regarding optimal radiation dose, chemotherapy agents, and how to combine these two adjuvant treatment modalities to achieve the best outcomes remain unanswered. In this paper we summarize the current management of CPC in the literature. Further studies are needed to standardize the treatment paradigm for this malignant brain tumor.


Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/therapy , Carcinoma/pathology , Carcinoma/therapy , Choroid Plexus Neoplasms/pathology , Choroid Plexus Neoplasms/therapy , Brain Neoplasms/diagnosis , Brain Neoplasms/epidemiology , Carcinoma/diagnosis , Carcinoma/epidemiology , Choroid Plexus Neoplasms/diagnosis , Choroid Plexus Neoplasms/epidemiology , Combined Modality Therapy/methods , Humans , Treatment Outcome
15.
Neuro Oncol ; 15(11): 1518-31, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23887941

ABSTRACT

BACKGROUND: Mechanisms of glioma invasion remain to be fully elucidated. Glioma cells within glioblastoma multiforme (GBM) range from well-differentiated tumor cells to less-differentiated brain tumor-initiating cells (BTICs). The ß2-subunit of Na(+)/K(+)-ATPase, called the adhesion molecule on glia (AMOG), is highly expressed in normal glia but is thought to be universally downregulated in GBM. To test our hypothesis that expression of AMOG is heterogeneous in GBM and confers a less invasive phenotype, we compared it between BTICs and differentiated cells from patient-matched GBM and then tested GBM invasion in vitro after AMOG overexpression. METHODS: Immunohistochemistry, immunoblotting, and real-time PCR were used to characterize AMOG protein and mRNA expression in tumor samples, BTICs, and differentiated cells. Matrigel invasion assay, scratch assay, and direct cell counting were used for testing in vitro invasion, migration, and proliferation, respectively. RESULTS: While AMOG expression is heterogeneous in astrocytomas of grades II-IV, it is lost in most GBM. BTICs express higher levels of AMOG mRNA and protein compared with patient-matched differentiated tumor cells. Overexpression of AMOG decreased GBM cell and BTIC invasion without affecting migration or proliferation. Knockdown of AMOG expression in normal human astrocytes increased invasion. CONCLUSIONS: AMOG expression inhibits GBM invasion. Its downregulation increases invasion in glial cells and may also represent an important step in BTIC differentiation. These data provide compelling evidence implicating the role of AMOG in glioma invasion and provide impetus for further investigation.


Subject(s)
Adenosine Triphosphatases/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cation Transport Proteins/metabolism , Cell Adhesion Molecules, Neuronal/metabolism , Glioblastoma/metabolism , Glioblastoma/pathology , Brain Neoplasms/mortality , Down-Regulation , Glioblastoma/mortality , Humans , Neoplasm Invasiveness , Survival Rate , Tumor Cells, Cultured
16.
J Clin Neurosci ; 20(10): 1390-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23768966

ABSTRACT

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p<0.001), grade I and II tumors did not differ significantly in outcomes following surgery. Overall, gross total resection (GTR, 68.7%, 114/166) provided significantly improved progression-free survival (PFS, p<0.001) and overall survival (OS, p=0.022) compared to the subtotal resection group. Surprisingly, the highest GTR rate was achieved for grade II tumors (78.8%, 78/99; p<0.001) followed by grade I (58.9%, 33/56) and grade III tumors (27.3%, 3/11). Interestingly, PFS was significantly improved by GTR for grade II tumors (p<0.001), but not for grade I (p=0.705). Similar trends, although not statistically significant, were found for OS. Our results show that while GTR provides the best overall outcomes, GTR is most effective for classic grade II ependymomas, but not for grade I ependymomas. Despite having a lower WHO grade, myxopapillary ependymomas have a lower GTR rate, and benefit less from GTR.


Subject(s)
Ependymoma/surgery , Neurosurgical Procedures/methods , Spinal Cord Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Databases, Bibliographic/statistics & numerical data , Disease-Free Survival , Ependymoma/mortality , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Spinal Cord Neoplasms/mortality , Trauma Severity Indices , Young Adult
17.
Childs Nerv Syst ; 29(11): 2057-64, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23677177

ABSTRACT

PURPOSE: Prognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS). METHODS: A comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included. RESULTS: A total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR) = 0.248, p = 0.022). Moreover, older age (HR = 0.818, p = 0.026), GTR (HR = 0.042, p = 0.013), and anaplastic grade (HR = 19.847, p = 0.008) demonstrated a significant association with OS in a multivariate model. CONCLUSIONS: Among pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.


Subject(s)
Ependymoma/surgery , Neurosurgical Procedures/methods , Spinal Cord Neoplasms/surgery , Adolescent , Age Factors , Child , Disease-Free Survival , Ependymoma/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Neoplasm Grading , Neoplasm Recurrence, Local , Spinal Cord Neoplasms/pathology , Treatment Outcome
18.
PLoS One ; 8(4): e62765, 2013.
Article in English | MEDLINE | ID: mdl-23658650

ABSTRACT

Mechanisms of invasion in glioblastoma (GBM) relate to differential expression of proteins conferring increased motility and penetration of the extracellular matrix. CD97 is a member of the epidermal growth factor seven-span transmembrane family of adhesion G-protein coupled receptors. These proteins facilitate mobility of leukocytes into tissue. In this study we show that CD97 is expressed in glioma, has functional effects on invasion, and is associated with poor overall survival. Glioma cell lines and low passage primary cultures were analyzed. Functional significance was assessed by transient knockdown using siRNA targeting CD97 or a non-target control sequence. Invasion was assessed 48 hours after siRNA-mediated knockdown using a Matrigel-coated invasion chamber. Migration was quantified using a scratch assay over 12 hours. Proliferation was measured 24 and 48 hours after confirmed protein knockdown. GBM cell lines and primary cultures were found to express CD97. Knockdown of CD97 decreased invasion and migration in GBM cell lines, with no difference in proliferation. Gene-expression based Kaplan-Meier analysis was performed using The Cancer Genome Atlas, demonstrating an inverse relationship between CD97 expression and survival. GBMs expressing high levels of CD97 were associated with decreased survival compared to those with low CD97 (p = 0.007). CD97 promotes invasion and migration in GBM, but has no effect on tumor proliferation. This phenotype may explain the discrepancy in survival between high and low CD97-expressing tumors. This data provides impetus for further studies to determine its viability as a therapeutic target in the treatment of GBM.


Subject(s)
Antigens, CD/genetics , Brain Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Antigens, CD/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Migration Assays , Cell Movement , Cell Proliferation , Gene Knockdown Techniques , Glioblastoma/metabolism , Glioblastoma/mortality , Glioblastoma/pathology , Humans , Neoplasm Invasiveness , Phenotype , Primary Cell Culture , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptors, G-Protein-Coupled , Survival Analysis
19.
J Neurosurg Spine ; 18(3): 226-35, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23311515

ABSTRACT

OBJECT: Ependymomas are primary central nervous system tumors that occur more frequently in the spines of adults than they do there in children. Previous studies consist mainly of retrospective single-institutional experiences or case studies. In this study, a comprehensive literature review was performed on reported cases of spinal ependymoma treated with resection to determine whether tumor location along the spinal axis conveys important prognostic information. METHODS: A PubMed search was performed to identify all papers that included data on patients with spinal ependymoma. Only cases involving adult patients who underwent ependymoma resection with a clearly reported tumor location were included for analysis. Tumor locations were separated into 6 groups: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus + cauda equina. Kaplan-Meier survival and Cox regression analyses were performed to determine the effect of tumor location on progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 447 patients who underwent resection of spinal ependymomas with clearly indicated location of tumor were identified. The most common locations of spinal ependymomas were the cervical (32.0%) and conus + cauda equina (26.8%) regions. The thoracolumbar and cervicomedullary regions had the fewest tumors (accounting for, respectively, 5.1% and 3.4% of the total number of cases). The conus + cauda equina and thoracolumbar regions had the highest percentage of WHO Grade I tumors, while tumors located above these regions consisted of mostly WHO Grade II tumors. Despite the tendency for benign grades in the lower spinal regions, PFS for patients with spinal ependymomas in the lower 3 regions (thoracic, thoracolumbar, conus + cauda equina) was significantly shorter (p < 0.001) than for those with tumors in the upper regions (cervicomedullary, cervical, cervicothoracic), but the difference in OS did not achieve statistical significance (p = 0.131). CONCLUSIONS: Spinal ependymomas along different regions of spinal axis have different characteristics and clinical behaviors. Tumor grade, extent of resection, and PFS varied by tumor location (upper vs lower spinal regions), while OS did not. Recurrence rates were higher for the lower spinal cord tumors, despite a greater prevalence of lower WHO grade lesions, compared with upper spinal cord tumors, suggesting that tumor location along the spinal axis is an important prognostic factor.


Subject(s)
Ependymoma/pathology , Ependymoma/surgery , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery , Adult , Humans , Neoplasm Grading , Neoplasm Staging , Prognosis , Proportional Hazards Models , Survival Analysis
20.
J Neurosurg Pediatr ; 11(3): 282-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23259510

ABSTRACT

OBJECT: Ependymoma is a common CNS tumor in children, with spinal cord ependymomas making up 13.1% of all ependymomas in this age group. The clinical features that affect prognosis in pediatric spinal cord ependymomas are not well understood. A comprehensive literature review was performed to determine whether a tumor location along the spinal cord is prognostically significant in children undergoing surgery for spinal cord ependymomas. METHODS: A PubMed search was performed to identify all papers that contained data on patients with spinal cord ependymomas. Only pediatric patients (age < 18 years) who underwent resection with a clearly reported tumor location were included in the analysis. Myxopapillary tumors were excluded from study. Tumor location was subdivided into 6 regions: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus medullaris. Kaplan-Meier survival and Cox regression analyses were performed to determine the effects of tumor location on progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-eight patients who underwent resection of spinal cord ependymomas were identified. Ependymomas were located all along the spinal cord but occurred with the highest frequency in the cervical region (29.3%). Progression-free survival was significantly better in patients with tumors arising in the upper portion of the spinal cord (p = 0.031), which remained significant in the multivariate Cox regression analysis (p < 0.05). Moreover, OS was significantly better in patients with upper spinal cord ependymomas than in those harboring ependymomas in the lower spinal cord (p = 0.048). CONCLUSIONS: Although more common in adults, spinal ependymomas can occur anywhere along the spinal cord in the pediatric population; however, tumors occurring in the lower half of the spinal cord carry a worse prognosis with shorter PFS and OS. By comparison, ependymomas in the upper spinal cord recur later and less frequently, with little or no mortality in this patient group.


Subject(s)
Ependymoma/pathology , Spinal Cord Neoplasms/pathology , Adolescent , Child , Child, Preschool , Disease-Free Survival , Ependymoma/surgery , Female , Humans , Kaplan-Meier Estimate , Male , Neurosurgical Procedures , Prognosis , Proportional Hazards Models , Spinal Cord Neoplasms/surgery , Survival Analysis , Treatment Outcome
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