Short-term outcomes associated with inpatient ventricular tachycardia catheter ablation.

BACKGROUND: Utilization of catheter ablation of ventricular tachycardia (VT) has steadily increased in recent years. Exploring short-term outcomes is vital in health care planning and resource allocation. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was queried using the ICD-9 codes for VT (427.1) and catheter ablation (37.34) to identify study population. Incidence, causes of 30-day readmission, in-hospital complications as well as predictors of 30-day readmissions, complications, and cost of care were analyzed. RESULTS: Among 11 725 patients who survived to discharge after index admission for VT ablation, 1911 (16.3%) were readmitted within 30 days. Paroxysmal VT was the most common cause of 30-day readmission (39.51%). Dyslipidemia, chronic kidney disease (CKD), previous CABG, congestive heart failure (CHF), chronic pulmonary disease, and anemia predicted increased risk of 30-day readmissions. The overall in-hospital complication rate was 8.2% with vascular and cardiac complications being the most common. Co-existing CKD and CHF and the need for mechanical circulatory support (MCS) predicted higher complication rates. Similarly increasing age, CKD, CHF, anemia, in-hospital use of MCS or left heart catheterization, teaching hospital, and disposition to nursing facilities predicted higher cost. CONCLUSION: Approximately one in six patients was readmitted after VT ablation, with paroxysmal VT being the most common cause of the readmission. A complication rate of 8.2% was noted. We also identified a predictive model for increased risk of readmission, complication, and factors influencing the cost of care that can be utilized to improve the outcomes related to VT ablation.

Correction: Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide.

The original version of this Article contained an error in the spelling of the author David Solow-Cordero, which was incorrectly given as David Solow-Codero. This has now been corrected in both the PDF and HTML versions of the Article.

Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Since surviving patients experience severe neurocognitive disabilities, better and more effective treatments are needed to enhance their quality of life. Casein kinase 2 (CK2) is known to regulate cell growth and survival in multiple cancers; however, the role of CK2 in MB is currently being studied. In this study, we verified the importance of CK2 in MB tumorigenesis and discovered that inhibition of CK2 using the small molecule inhibitor, CX-4945, can sensitize MB cells to a well-known and tolerated chemotherapeutic, temozolomide (TMZ). To study the role of CK2 in MB we modulated CK2 expression in multiple MB cells. Exogenous expression of CK2 enhanced cell growth and tumor growth in mice, while depletion or inhibition of CK2 expression decreased MB tumorigenesis. Treatment with CX-4945 reduced MB growth and increased apoptosis. We conducted a high-throughput screen where 4000 small molecule compounds were analyzed to identify compounds that increased the anti-tumorigenic properties of CX-4945. TMZ was found to work synergistically with CX-4945 to decrease cell survival and increase apoptosis in MB cells. O-6-methylguanine-DNA methyltransferase (MGMT) activity is directly correlated to TMZ sensitivity. We found that loss of CK2 activity reduced ß-catenin expression, a known MGMT regulator, which in turn led to a decrease in MGMT expression and an increased sensitivity to TMZ. Our findings show that CK2 is important for MB maintenance and that treatment with CX-4945 can sensitize MB cells to TMZ treatment.

Immune Evasion Strategies of Glioblastoma.

Glioblastoma (GBM) is the most devastating brain tumor, with associated poor prognosis. Despite advances in surgery and chemoradiation, the survival of afflicted patients has not improved significantly in the past three decades. Immunotherapy has been heralded as a promising approach in treatment of various cancers; however, the immune privileged environment of the brain usually curbs the optimal expected response in central nervous system malignancies. In addition, GBM cells create an immunosuppressive microenvironment and employ various methods to escape immune surveillance. The purpose of this review is to highlight the strategies by which GBM cells evade the host immune system. Further understanding of these strategies and the biology of this tumor will pave the way for developing novel immunotherapeutic approaches for treatment of GBM.

γ-Glutamyl transferase 7 is a novel regulator of glioblastoma growth.

BACKGROUND: Glioblastoma (GBM) is the most malignant primary brain tumor in adults, with a median survival time of one and a half years. Traditional treatments, including radiation, chemotherapy, and surgery, are not curative, making it imperative to find more effective treatments for this lethal disease. γ-Glutamyl transferase (GGT) is a family of enzymes that was shown to control crucial redox-sensitive functions and to regulate the balance between proliferation and apoptosis. GGT7 is a novel GGT family member that is highly expressed in brain and was previously shown to have decreased expression in gliomas. Since other members of the GGT family were found to be altered in a variety of cancers, we hypothesized that GGT7 could regulate GBM growth and formation. METHODS: To determine if GGT7 is involved in GBM tumorigenesis, we modulated GGT7 expression in two GBM cell lines (U87-MG and U138) and monitored changes in tumorigenicity in vitro and in vivo. RESULTS: We demonstrated for the first time that GBM patients with low GGT7 expression had a worse prognosis and that 87% (7/8) of primary GBM tissue samples showed a 2-fold decrease in GGT7 expression compared to normal brain samples. Exogenous expression of GGT7 resulted in a 2- to 3-fold reduction in proliferation and anchorage-independent growth under minimal growth conditions (1% serum). Decreasing GGT7 expression using either short interfering RNA or short hairpin RNA consistently increased proliferation 1.5- to 2-fold. In addition, intracranial injections of U87-MG cells with reduced GGT7 expression increased tumor growth in mice approximately 2-fold, and decreased mouse survival. To elucidate the mechanism by which GGT7 regulates GBM growth, we analyzed reactive oxygen species (ROS) levels in GBM cells with modulated GGT7 expression. We found that enhanced GGT7 expression reduced ROS levels by 11-33%. CONCLUSION: Our study demonstrates that GGT7 is a novel player in GBM growth and that GGT7 can play a critical role in tumorigenesis by regulating anti-oxidative damage. Loss of GGT7 may increase the cellular ROS levels, inducing GBM occurrence and growth. Our findings suggest that GGT7 can be a promising biomarker and a potential therapeutic target for GBM.

Intracranial fat migration: A newly described complication of autologous fat repair of a cerebrospinal fluid leak following supracerebellar infratentorial approach.

INTRODUCTION: Intracranial fat migration following autologous fat graft and placement of a lumbar drain for cerebrospinal fluid leak after pineal cyst resection surgery has not been previously reported. CASE PRESENTATION: The authors present a case of a 39-year-old male with a history of headaches who presented for removal of a pineal cyst from the pineal region. He subsequently experienced cerebrospinal fluid leak and postoperative Escherichia coli (E. Coli) wound infection, and meningitis, which were treated initially with wound washout and antibiotics in addition to bone removal and primary repair with primary suture-closure of the durotomy. A lumbar drain was left in place. The cerebrospinal fluid leak returned two weeks following removal of the lumbar drain; therefore, autologous fat graft repair and lumbar drain placement were performed. Three days later, the patient began experiencing right homonymous hemianopia and was found via computed tomography and magnetic resonance imaging to have autologous fat in the infra­ and supratentorial space, including intraparenchymal and subarachnoid spread. Symptoms began to resolve with supportive care over 48 hours and had almost fully resolved within one week. DISCUSSION: This is the first known report of a patient with an autologous fat graft entering the subarachnoid space, intraparenchymal space, and ventricles following fat graft and lumbar drainage. CONCLUSION: This case highlights the importance of monitoring for complications of lumbar drain placement.