Impact of Tumor Burden on Quantitative [68Ga] DOTATOC Biodistribution

Molecular Imaging and Biology - As has been previously reported, the somatostatin receptor (SSTR) imaging agent [68Ga]-labeled...     

Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy

Purpose

Early identification of aggressive disease could improve decision support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT was analyzed.

Procedures

Thirty-one patients with G1/G2 pNET were enrolled (G2, n?=?23/31). Prior to PRRT with [¹⁷⁷Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET computed tomography was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV_mean/max), imaging-based TF, and clinical parameters (Ki67, CgA) for prediction of both progression-free survival (PFS) and overall survival (OS) after PRRT were evaluated.

Results

Within a median follow-up of 3.7 years, tumor progression was detected in 21 patients (median, 1.5 years) and 13/31 deceased (median, 1.9 years). In ROC analysis, the TF entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff?=?6.7, AUC?=?0.71, p?=?0.02). Of note, increasing entropy could predict a longer survival (>?6.7, OS?=?2.5 years, 17/31), whereas less voxel-based derangement portended inferior outcome (<?6.7, OS?=?1.9 years, 14/31). These findings were supported in a G2 subanalysis (>?6.9, OS?=?2.8 years, 9/23 vs. <?6.9, OS?=?1.9 years, 14/23). Kaplan–Meier analysis revealed a significant distinction between high- and low-risk groups using entropy (n?=?31, p?<?0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n?=?31, p?=?0.04). Ki67 was negatively associated with PFS (p?=?0.002); however, SUV_mean/max failed in prognostication (n.s.).

Conclusions

In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.

     

Catheter Ablation of Arrhythmias Exclusively Using Electroanatomic Mapping: A Series of Cases

Background

Catheter ablation is a treatment that can cure various cardiac arrhythmias. Fluoroscopy is used to locate and direct catheters to areas that cause arrhythmias. However, fluoroscopy has several risks. Electroanatomic mapping (EAM) facilitates three-dimensional imaging without X-rays, which reduces risks associated with fluoroscopy.

Objective

We describe a series of patient cases wherein cardiac arrhythmia ablation was exclusively performed using EAM.

Methods

Patients who presented with cardiac arrhythmias that were unresponsive to pharmacological therapy were prospectively selected between March 2011 and March 2012 for arrhythmia ablation exclusively through EAM. Patients with indications for a diagnostic electrophysiology study and ablation of atrial fibrillation, left atrial tachyarrhythmias as well as hemodynamically unstable ventricular arrhythmia were excluded. We documented the procedure time, success rate and complications as well as whether fluoroscopy was necessary during the procedure.

Results

In total, 11 patients were enrolled in the study, including seven female patients (63%). The mean age of the patients was 50 years (SD ±16.5). Indications for the investigated procedures included four cases (35%) of atrial flutter, three cases (27%) of pre-excitation syndrome, two cases (19%) of paroxysmal supraventricular tachycardia and two cases (19%) of ventricular extrasystoles. The mean procedure duration was 86.6 min (SD ± 26 min). Immediate success (at discharge) of the procedure was evident for nine patients (81%). There were no complications during the procedures.

Conclusion

This study demonstrates the feasibility of performing an arrhythmia ablation exclusively using EAM with satisfactory results.     

Trophic control of cholinesterase activity in a testosterone-dependent muscle of the rat: Effects of castration and denervation

The effects of testosterone withdrawal and chronic denervation on muscle weight and acetylcholinesterase (AChE) activity were studied in the hormone-sensitive levator ani muscle of the rat. Castration of adult male rats for 7 to 60 days caused a linear decrease of the weight, protein content, and AChE activity of the muscle, which stabilized after 30 days. Muscle weight and protein content decreased 2.3% per day. The total AChE activity decreased 7 days later 3.2% per day, reaching 37% of control at day 30. AChE activity per unit weight was increased in all castrated groups. Muscle weights and AChE activity of the extensor digitorum longus and soleus muscles were not altered after castration. Denervation of all three muscles caused 50% reduction of the muscle weight and protein content after 15 days. Total AChE activity decayed exponentially with a rate of 0.12 per day to 15 to 18% of control values. AChE activity per unit weight in the denervated muscles was always lower than in the control muscles. Combined castration and denervation intensified only the levator ani protein loss. The different onset and time course of the effects induced by castration and denervation indicate distinct mechanisms involved in the trophic control of muscle proteins and AChE activity. Chronic muscle denervation decreased total AChE activity to 15% of normal, whereas castration reduced the enzyme to 40% of the control values. The results indicate that neuronal and hormonal influences on AChE activity of the levator ani are not additive but overlap.     

Effects of histrionicotoxin on the chemosensitive and electrical properties of skeletal muscle

Histrionicotoxin (HTX), a spiropiperidine alkaloid from the Colombian frog, Dendrobates histrionicus, has a variety of effects on the function of mammalian and amphibian nerve-muscle preparations. At a concentration of 70 × 10⁻⁶m, HTX blocks indirectly elicited muscle twitches in the mouse phrenic nerve-diaphragm preparation within 20 min, while potentiating directly elicited twitches. Resting membrane potential and passive electrical properties are little affected by the drug. HTX prolongs the falling phase of the action potential and blocks delayed rectification, indicating that the potassium conductance is suppressed. Endplate potentials are also blocked by the toxin, and the onset of this blockade is dependent on the frequency of stimulation. Similarly, HTX decreases the sensitivity of denervated mammalian skeletal muscles to repetitive applications of acetylcholine, the degree of blockade also being dependent on the rate and duration of iontophoretic application of acetylcholine. All effects of HTX are reversed by washing the muscle. HTX does not prevent the irreversible effects of an acetylcholine antagonist, α-bungarotoxin, in the mouse phrenic nerve-diaphragm preparation. It is suggested that HTX acts on the ionic conductance modulator of the acetylcholine receptor in a manner similar to its semisynthetic derivative perhydrohistrionicotoxin.     

Permanent inflation of detachable balloons with a low-viscosity, hydrophilic polymerizing system

A polymer system was developed for use in permanent inflation of detachable balloons, to avoid long-term reliance on the integrity of balloon shells or valve mechanisms. This system is based on 2-hydroxy-ethyl methacrylate (HEMA) as the monomer, in combination with a cross-linking agent and a water-soluble curing system. The low-viscosity, hydrophilic mixture can be exchanged through a small-bore catheter into a detachable balloon and polymerizes in 40-60 minutes at body temperature. Partially polymerized HEMA can cause vascular occlusion; hence, careful timing of balloon detachment is required. The evolution of the radiographic appearance of HEMA-filled balloons is predictable. The balloons remain radiopaque on plain radiographs as long as the balloon shell and valve mechanisms are competent. After rupture of the shell or failure of the valve mechanism, the balloons become invisible on plain radiographs but remain hyperattenuating on computed tomography scans.     

Problems of Psychological Monitoring in Astronaut Training

在进行职业训练时，对受训者的心理变化趋势进行监视是必要的。航天员心理因素的发展水平可通过心理测试来检测，以便能对其重要的心理指标进行评价，并给出综合评价。文中列出应进行测试的心理指标，并根据大量的样本统计给出了经验加权因子。测试结果的积累可以预测航天员将来飞行任务中处理复杂问题的能力，并能帮助改进训练过程及暴露缺点。     

Timbós: ichthyotoxic plants used by brazilian indians

The pharmacology of serjanosides, active principles isolated from the fishpoison plant Serjania lethalis St. Hil, a Sapindaceae, was investigated by comparing their actions in fishes and mammals with those of rotenone and certain saponins. The ichthyocid activity of the serjanosides was 2.5 times greater than that of the crude plant extract, approximately 10 times lower than the activity of rotenone, but from 10 to 50 times greater than the activity of the other saponins. When injected in mammals, the serjanosides induced deep prostration, dyspnea, cyanosis, ectopic heart beats, cardiovascular failure and respiratory arrest. These effects, leading to death that was not prevented by artificial respiration, indicated several mechanisms for the toxic action of the serjanosides. In vitro studies with these substances have shown that membrane depolarization and muscle contracture were probably due to unspecific surface actions. Rotenone, under the same experimental conditions induced hypotension, bradycardia and respiratory arrest. Death was prevented by artificial respiration. Ectopic foci, membrane depolarization, contractures and neuromuscular block were not observed after rotenone. Apparently, death from rotenone poisoning was a consequence of respiratory failure of central origin.

The serjanosides are rather potent fish poison saponins. Mammals, however, are apparently insensitive to the same specific action since other toxic effects induced by those substances in rats and mice were also observed by employing saponins devoid of fish-killing activity.