Reliability of the Modified TICI Score among Endovascular Neurosurgeons.

BACKGROUND AND PURPOSE: The modified TICI score is the benchmark for quantifying reperfusion after mechanical thrombectomy. There has been limited investigation into the reliability of this score. We aim to identify intra-rater and inter-rater reliability of the mTICI score among endovascular neurosurgeons. MATERIALS AND METHODS: Four independent endovascular neurosurgeons (raters) reviewed angiograms of 67 patients at 2 time points. κ statistics assessed inter- and intrarater reliability and compared raters'-versus-proceduralists' scores. Reliability was also assessed for occlusion location and by dichotomizing modified TICI scores (0-2a versus 2b-3). RESULTS: Interrater reliability was moderate-to-substantial, weighted κ = 0.417-0.703, overall κ = 0.374 (P < .001). The dichotomized modified TICI score had moderate-to-substantial interrater agreement, κ statistics = 0.468-0.715, overall κ = 0.582 (P < .001). Intrarater reliability was moderate-to-almost perfect, weighted κ = 0.594-0.81. The dichotomized modified TICI score had substantial-to-almost perfect reliability, κ = 0.632-0.82. Proceduralists had fair-to-moderate agreement with raters, weighted κ = 0.348-0.574, and the dichotomized modified TICI score had fair-to-moderate agreement, κ = 0.365-0.544. When proceduralists and raters disagreed, proceduralists' scores were higher in 79.6% of cases. M1 followed by ICA occlusions had the highest agreement. CONCLUSIONS: The modified TICI score is a practical metric for assessing reperfusion after mechanical thrombectomy, though not without limitations. Agreement improved when scores were dichotomized around the clinically relevant threshold of successful revascularization. Interrater reliability improved with time, suggesting that formal training of interventionalists may improve reporting reliability. Agreement of the modified TICI scale is best with M1 and ICA occlusion and becomes less reliable with more distal or posterior circulation occlusions. These findings should be considered when developing research trials.

Control of glutamine metabolism by the tumor suppressor Rb.

Retinoblastoma (Rb) protein is a tumor suppressor that is dysregulated in a majority of human cancers. Rb functions to inhibit cell cycle progression in part by directly disabling the E2F family of cell cycle-promoting transcription factors. Because the de novo synthesis of multiple glutamine-derived anabolic precursors is required for cell cycle progression, we hypothesized that Rb also may directly regulate proteins involved in glutamine metabolism. We examined glutamine metabolism in mouse embryonic fibroblasts (MEFs) isolated from mice that have triple knock-outs (TKO) of all three Rb family members (Rb-1, Rbl1 and Rbl2) and found that loss of global Rb function caused a marked increase in (13)C-glutamine uptake and incorporation into glutamate and tricarboxylic acid cycle (TCA) intermediates in part via upregulated expression of the glutamine transporter ASCT2 and the activity of glutaminase 1 (GLS1). The Rb-controlled transcription factor E2F-3 altered glutamine uptake by direct regulation of ASCT2 mRNA and protein expression, and E2F-3 was observed to associate with the ASCT2 promoter. We next examined the functional consequences of the observed increase in glutamine uptake and utilization and found that glutamine exposure potently increased oxygen consumption, whereas glutamine deprivation selectively decreased ATP concentration in the Rb TKO MEFs but not the wild-type (WT) MEFs. In addition, TKO MEFs exhibited elevated production of glutathione from exogenous glutamine and had increased expression of gamma-glutamylcysteine ligase relative to WT MEFs. Importantly, this metabolic shift towards glutamine utilization was required for the proliferation of Rb TKO MEFs but not for the proliferation of the WT MEFs. Last, addition of the TCA cycle intermediate α-ketoglutarate to the Rb TKO MEFs reversed the inhibitory effects of glutamine deprivation on ATP, GSH levels and viability. Taken together, these studies demonstrate that the Rb/E2F cascade directly regulates a major energetic and anabolic pathway that is required for neoplastic growth.

Atrial fibrillation: epidemiology, prognosis and therapy.

Atrial fibrillation is the most common cardiac tachyarrhythmia encountered in clinical practice affecting 1% of the population. It is characterized by uncoordinated atrial activation that can lead to embolic complications and reduction in cardiac output resulting in significant morbidity, mortality and a reduction in quality of life. The three major goals in the management of atrial fibrillation are rate control, prevention of thromboembolism and correction of rhythm disturbance. This article will review up-to-date thinking about strategies for achieving each of these fundamental goals of AF care, with an emphasis on new drugs such as dabigatran and dronedarone and emerging non-pharmacologic therapies such as catheter ablation and left atrial appendage exclusion. After many years with relatively few new treatments, the past few years have seen a number of exciting developments which will hopefully improve clinician's ability to improve the outcomes of patients with this chronic and troublesome condition.

The Gibberellin Status of lip1, a Mutant of Pea That Exhibits Light-Independent Photomorphogenesis.

Dark-grown seedlings of the lip1 (light independent photomorphogenesis) mutant of Pisum sativum L. display many features of de-etiolated growth and are similar in many respects to wild-type (WT) seedlings grown in the light. The involvement of gibberellins (GAs) with the mutant phenotype was examined by applying GA1 and GA20 to the mutant and WT, and by quantifying endogenous GA1, GA8, GA19, GA20, and GA29 levels in the two genotypes. These experiments were conducted in both the light and the dark. In neither environment could GA application restore elongation in the mutant to that in GA-treated WT plants. Quantification of GAs provided further evidence that the mutant phenotype is not attributable to a deficiency in endogenous GA1. However, dark-grown lip1 seedlings contained lower levels of GA19 and higher levels of GA20 than dark-grown WT plants, whereas in the light, the effect of the mutation on the ratio of GA19 to GA20 was reversed. Thus, there appears to be a complex interaction between the lip1 mutation, the light regime, and the step GA19 to GA20.

Hazards to the orthopaedic trauma surgeon: occupational exposure to tuberculosis. Risk reduction, testing, and treatment (a review article).

Infection with tuberculosis (TB) in the United States has risen over the last decade. In the past 5 years, health care worker exposure to multidrug-resistant TB has lead to more than 100 skin-test conversions, 17 cases of active TB, and at least six deaths. As with human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, the orthopaedic traumatologist is at risk of exposure and infection because, in many cases, the medical histories of patients encountered in the trauma bay cannot be determined until well into the course of care. Risk depends principally on two factors: (a) likelihood of exposure (large urban settings, prisons, concentration of persons from countries with high TB prevalence), and (b) immune status of the surgeon. Prompt recognition, isolation, and appropriate treatment of patients with infectious TB; engineering controls; and the use of personal protective respiratory equipment can help prevent the transmission of TB to health care workers.

Hazards to the orthopaedic trauma surgeon: occupational exposure to HIV and viral hepatitis (a review article).

The risk of transmission of blood-borne pathogens is directly related to the prevalence of the infectious disease in the physician's patient population, the infectivity after a single exposure, and the frequency and nature of exposure. After reading this material the reader should understand the guidelines for risk prevention of human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus transmission as published by the Centers for Disease Control and Prevention (CDC) and the Occupational Safety and Health Administration (OSHA) and be better able to evaluate and choose personal protective devices for use while caring for patients. To date there have been no documented cases of HIV seroconversion from solid-bore needle puncture or aerosolized transmission from an HIV-positive patient to a physician in the operating room. However, the authors and the Orthopaedic Trauma Association urge all physicians who have sustained an occupational seroconversion to communicate with the CDC so that prevention guidelines and health-care worker protection can be improved. Regardless, all physicians performing invasive procedures must reevaluate their techniques to determine what procedures can be modified or new instruments developed to reduce the risk of exposure.

Finite-element analysis of thermal stresses in the single-mode bonded splice.

Extremely low-loss single-mode optical fiber splices made with an AT&T bonded design permit longer unrepeatered spans. Average losses of less than 0.05 dB have been achieved in the field by ordinary cable splicers. The splices were designed for stability over a wide range of temperatures using finite-element analysis techniques. This analysis permitted optimization of the splice geometry and material selection for performance over a temperature range of -40 to 77 degrees C. Environmental testing demonstrates that the design performs as predicted when cycled over this extreme temperature range, with no added loss incurred after any testing. This combination of design analysis and thorough environmental testing ensures the reliability of the single-mode bonded splice.