Radiofrequency lesioning through deep brain stimulation electrodes: A pilot study of lesion geometry and temperature characteristics

Deep brain stimulation (DBS) electrodes have been used effectively to perform radiofrequency lesions in the brain. This study aimed to characterize lesion geometry and peak tissue temperature achieved when lesioning through DBS electrodes. Fresh bovine liver was chosen for a medium as the tissue reliably changes color between 45 and 50°C. Medtronic 3387 DBS electrodes (Medtronic Sofamor Danek, Inc., Memphis, TN, USA) and the Cosman G4 Radiofrequency Generator (Cosman Medical, Inc., Burlington, MA, USA) were used for lesioning. Bipolar lesions were created at currents between 25 mA and 100 mA for 60–120 seconds. Peak tissue temperature was monitored with Cosman disposable cordotomy electrode (LCED; Cosman Medical Inc.) and recorded. Photographic analysis of the lesions was performed. Tissue impedance ranged between 800–900 Ohms, and tissue temperature was maintained at 20°C. With lesions at 25 mA for up to 120 seconds, maximal tissue temperature achieved was 36°C. This correlated with no visible lesions. At 50 mA, maximal tissue temperature exceeded 100°C, which was associated with tissue charring. Lesions created at 35 mA and 40 mA led to an increase in tissue temperature of 63°C and 75°C, respectively. Lesion size was highly reproducible, increasing from 4.5 mm × 7 mm at 35 mA, to 6 mm × 7.5 mm at 50 mA. Preliminary analysis suggests that caution should be exerted in using lesion amplitudes exceeding 40 mA (at 800 Ohms), as peak tissue temperatures in vivo could exceed 100°C. Further in vivo experiments with imaging correlates are needed to further test the safety of this technique.     

Understanding the underutilization of cervical brachytherapy for locally advanced cervical cancer

PurposeTo understand the reasons behind current low utilization of brachytherapy for locally advanced cervical cancer in the United States.Methods and MaterialsA 17-item survey was e-mailed to the American Brachytherapy Society (ABS) listserv of active members in 2018. Responses of attending physicians in the United States were included in the analysis.ResultsAmong a total of 135 respondents, 81 completed the survey. Eighty-four percent agree/strongly agree that cervical brachytherapy is underutilized, and 46.9% disagree/strongly disagree that residents are receiving adequate training for brachytherapy; 75.3% agree/strongly agree that inadequate maintenance of brachytherapy skills is a major obstacle to brachytherapy use; and 71.6% agree/strongly agree that increased time requirement constitutes a major obstacle. Over 97% will recommend brachytherapy for most patients with cervical cancer if given access/time; 72.8% always perform their own brachytherapy, whereas 29.6% reported some type of barrier exists in performing brachytherapy themselves, with time required to perform brachytherapy (9.9%) being a leading factor. A quarter (24.7%) routinely refer to other radiation oncologists for brachytherapy. Even among ABS members, 37.0% reported that they would perform an intensity-modulated radiation therapy or stereotactic body radiation therapy boost in specific scenarios in potentially curable patients. The most common scenario is inability to place a uterine tandem (56.7%).ConclusionsThe underutilization of brachytherapy in cervical cancer is widely recognized by ABS members with inadequate training during residency and inadequate maintenance of skills being possible major contributing factors. Even among ABS members, there are identifiable barriers. Continued advocacy and future initiatives in enhancing access to brachytherapy training and efficiency are needed.     

Comorbidity indices for clinical trials: adaptation of two existing indices for use with the FREEDOM trial in women with postmenopausal osteoporosis

Summary

Two comorbidity indices were adapted for use in the FREEDOM trial and significantly correlated with the number of medications and impaired health status at baseline. The indices have applications for the analysis of clinical trial data and would allow for the appropriate adjustment of comorbidities when evaluating clinical trial outcomes.

Introduction

The purpose of this study is to adapt two published comorbidity indices for use with the FREEDOM clinical trial evaluating postmenopausal women with osteoporosis.

Methods

FREEDOM enrolled women aged 60–90 years with a bone mineral density T-score <?2.5 at the lumbar spine or total hip and ≥?4.0 at both sites. Comorbidity indices were calculated using methods described by Sangha (Arthritis Rheum 49:156–163, 2003) and Wolfe (J Rheumatol 37:305–315, 2010) following modification. The adapted Sangha index included 12 conditions with a summary score of 0–12; the adapted Wolfe index included 7 conditions with a weighted summary score of 0–8. Higher scores indicated greater comorbidity. A panel of clinicians independently reviewed subjects’ medical histories using a systematic process based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to map specified comorbid conditions. Spearman correlations between the adapted indices and baseline subject characteristics expected to be associated with comorbidities were examined.

Results

Of the 7808 subjects in this study, 74 % had ≥1 comorbidities based on the adapted Sangha or Wolfe comorbidity indices. The mean (SD) adapted Sangha and Wolfe comorbidity indices were 1.4 (1.2) and 1.4 (1.3), respectively. Both indices correlated positively with age, body mass index, and the number of medications (r?=?0.54 to 0.55) at baseline and inversely correlated with health-related quality of life (r?=??0.22 to ?0.30) (all P?<?0.0001). Further, when either the adapted Sangha or Wolfe index was included as a covariate for assessing mortality over 36 months in the FREEDOM population, the hazard ratio of the comorbidity index indicated that the mortality risk increased by 27 or 28 %, respectively, for each unit increase in the adapted index (both P?<?0.0001).

Conclusions

Our work suggests these comorbidity indices may be adapted for use with clinical trial data, thereby allowing for the appropriate adjustment and reporting of covariates in the evaluation of clinical trial outcomes in an osteoporotic population.

     

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.     

Cardioprotective effect of oleanolic acid on isoproterenol-induced myocardial ischemia in rats

This study was designed to investigate the protective effect of oleanolic acid (OA) against isoproterenol-induced myocardial ischemia in rat myocardium. Wistar strain rats were pretreated with OA (20, 40, and 60 mg/kg, s.c) for 7 days and then intoxicated with isoproterenol (ISO, 85 mg/kg, sc for 2 consecutive days). Heart were excised from the experimental animals and assessed for the activities of marker enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)], the levels of lipid peroxide products [thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD)], myeloperoxidase (MPO), lipid profiles [total cholesterol (TC), free cholesterol, ester cholesterol, triglycerides (TG), free fatty acids (FFA) and phospholipids (PL)], and membrane-bound ATPase enzymes (total ATPase, Na(+)K(+) ATPase, Ca(2 +) ATPase, and Mg(2 +) ATPase). Troponin T and I were estimated in plasma. Leakage of cardiac markers, elevated lipid peroxidation with increased lipid profiles and decreased activities of membrane-bound ATPase enzymes were confirmed the severe myocardial damage occurring as a consequence of isoproterenol-induced ischemia, and they also showed the significant improvement effected by oleanolic acid pretreatment. These findings provided evidence that oleanolic acid was found to be protecting rat myocardium against ischemic insult and the protective effect could attribute to its anti-oxidative, anti-hyperlipedemic, and anti-arrhythmic properties as well as its membrane-stabilizing action.     

Yohimbine administration and cue-reactivity in cocaine-dependent individuals

Rationale

Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations.

Objectives

The objectives of this study were to examine the impact a pharmacological stressor, alpha-2 adrenergic receptor antagonist yohimbine, on the subjective, endocrine, and physiologic responses to drug-paired cues cocaine-dependent men and women.

Methods

In a double-blind placebo-controlled cross-over study, cocaine-dependent men (n?=?32), cocaine-dependent women (n?=?30), control men (n?=?32), and control women (n?=?25) received either yohimbine or placebo prior to two cocaine cue exposure sessions.

Results

Yohimbine increased ratings of anxiety both before (p?p?=?0.035) cues, and the post-cue increase in anxiety was more pronounced in women (p?=?0.001). Yohimbine also significantly increased craving, compared with placebo (p?p?=?0.006). Yohimbine also increased salivary cortisol (p?p?=?0.003) levels, regardless of diagnostic group. Women had a significantly greater heart rate response following yohimbine as compared with men (p?Conclusions Stress may increase the salience of cocaine cues for cocaine-dependent women as compared with men. This suggests gender differences in vulnerability to craving and relapse under stressful conditions.     

Synthesis and Characterization of a Nearly Single Bulk Ti2AlN MAX Phase Obtained from Ti/AlN Powder Mixture through Spark Plasma Sintering

MAX phases are an advanced class of ceramics based on ternary carbides or nitrides that combine some of the ceramic and metallic properties, which make them potential candidate materials for many engineering applications under severe conditions. The present work reports the successful synthesis of nearly single bulk Ti₂AlN MAX phase (>98% purity) through solid-state reaction and from a Ti and AlN powder mixture in a molar ratio of 2:1 as starting materials. The mixture of Ti and AlN powders was subjected to reactive spark plasma sintering (SPS) under 30 MPa at 1200 °C and 1300 °C for 10 min in a vacuum atmosphere. It was found that the massive formation of Al₂O₃ particles at the grain boundaries during sintering inhibits the development of the Ti₂AlN MAX phase in the outer zone of the samples. The effect of sintering temperature on the microstructure and mechanical properties of the Ti₂AlN MAX phase was investigated and discussed.