MRI evaluation of complex renal cysts using the Bosniak classification: a comparison to CT

Purpose

The purpose of this study was to compare the ability of magnetic resonance imaging (MRI) and computed tomography (CT) to discriminate between benign and malignant cystic renal lesions utilizing the Bosniak classification.

Materials and Methods

We retrospectively searched our Radiological Information System using renal/kidney cysts as entries. The search retrieved 2929 patients and 525 complex renal cysts. After exclusions, 42 complex cysts, from 37 patients, with CT and MRI, up to six months apart, were included. Surgery and pathology report and follow-up of at least 24 months were used as a standard of reference.

Results

The mean age of patients was 51.4 years, ranging from 11 to 82 years old. Twenty-nine lesions were classified as Bosniak I, II or II-F by CT and/or MRI and 13 as Bosniak III or IV, by one of the methods. The interobserver agreement for Bosniak classification for CT was 0.87 and 0.93 for MRI. Fifteen lesions had higher Bosniak categories on MRI, included six with change in management. Only two lesions had a higher category on CT, one with change in management. The frequency of malignancy for Bosniak III was 50 % (2/4) for CT and 20% for MRI (1/5), as Bosniak upgrades by MRI resulted in surgery for benign lesions. Both methods had 100 % frequency of malignancy for category 4.

Conclusion

MRI led to category migration and management change of complex renal cysts in a significant proportion of cases, likely due to its superior soft tissue and contrast resolution. The impact of MRI on detection and outcomes of malignant complex renal cysts still requires further investigation.

     

Drug Solubilization by Means of a Surface-Modified Edible Biopolymer Enabled by Hot Melt Extrusion

A coprocessing/formulation approach for increasing the solubility of poorly soluble drugs using solid dispersions is presented, whereby the active pharmaceutical ingredients (API) retains its crystalline state. The approach uses a biopolymer naturally produced as dendrimeric nanoparticles that has been surface-modified to act as a solubilizing agent. The solubilizing agent is enabled by hot melt extrusion to produce the solid dispersions. Four APIs, phenytoin (PHT), griseofulvin, ibuprofen, and loratadine were used as model compounds to evaluate solubility enhancement. The rank order in solubility enhancement follows that of the hydrophobicity of the APIs. The APIs remained predominantly crystalline after hot melt extrusion processing. However, APIs with weak crystal structure (ibuprofen and loratadine) underwent measurable crystallinity loss. The solubilizing power of the modified biopolymer increases with increasing hydrophobicity and strength of the crystal structure. The solubility is described in terms of a parallel liquid-phase partition-association. For one API (PHT), solubility enhancement was minimal. The dissimilar behavior of PHT is discussed in terms of the polarity match between the API and the hydrophobic microenvironment in the solubilizing agent. This approach is expected to apply to a large number of poorly soluble drugs, offering a complementary approach to existing processing and formulation drug solubilization methods.     

Pharmacotherapy for the treatment of depression in patients with alzheimer’s disease: a treatment-resistant depressive disorder

Introduction: Pharmacotherapy for the treatment of depressive disorders in Alzheimer’s Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8–12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects.

Areas covered: The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine.

Expert opinion: The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.     

A Novel Method for Determining the Solubility of Small Molecules in Aqueous Media and Polymer Solvent Systems Using Solution Calorimetry

Purpose

To explore the application of solution calorimetry for measuring drug solubility in experimentally challenging situations while providing additional information on the physical properties of the solute material.

Methods

A semi-adiabatic solution calorimeter was used to measure the heat of dissolution of prednisolone and chlorpropamide in aqueous solvents and of griseofulvin and ritonavir in viscous solutions containing polyvinylpyrrolidone and N-ethylpyrrolidone.

Results

Dissolution end point was clearly ascertained when heat generation stopped. The heat of solution was a linear function of dissolved mass for all drugs (<10% RSD, except for chlorpropamide). Heats of solution of 9.8?±?0.8, 28.8?±?0.6, 45.7?±?1.6 and 159.8?±?20.1 J/g were obtained for griseofulvin, ritonavir, prednisolone and chlorpropamide, respectively. Saturation was identifiable by a plateau in the heat signal and the crossing of the two linear segments corresponds to the solubility limit. The solubilities of prednisolone and chlopropamide in water by the calorimetric method were 0.23 and 0.158 mg/mL, respectively, in agreement with the shake-flask/HPLC-UV determined values of 0.212?±?0.013 and 0.169?±?0.015 mg/mL, respectively. For the higher solubility and high viscosity systems of griseofulvin and ritonavir in NEP/PVP mixtures, respectively, solubility values of 65 and 594 mg/g, respectively, were obtained.

Conclusion

Solution calorimetry offers a reliable method for measuring drug solubility in organic and aqueous solvents. The approach is complementary to the traditional shake-flask method, providing information on the solid properties of the solute. For highly viscous solutions, the calorimetric approach is advantageous.     

Catheter ablation of common-type atrial flutter guided by three-dimensional right atrial geometry reconstruction and catheter tracking using cutaneous patches: a randomized prospective study

INTRODUCTION: EnSite NavX (NavX) is a novel mapping and navigation system that allows visualization of conventional catheters for diagnostic and ablative purposes and uses them to create a three-dimensional (3D) geometry of the heart. NavX is particularly suitable for ablation procedures utilizing an anatomic approach, as in the setting of common-type atrial flutter (AFL). The aim of this study was to compare NavX-guided and conventional ablation procedures for AFL. METHODS AND RESULTS: Forty consecutive patients (32 male, 59 +/- 12 years) with documented AFL were randomized to undergo fluoroscopy-guided (group I, 20 patients) or NavX-guided (group II, 20 patients) ablation, including 3D isthmus reconstruction. The same catheter setup was used in both groups. The endpoint of bidirectional isthmus block was obtained in all patients. Compared to conventional approaches, NavX-guided procedures significantly reduced fluoroscopy time (5.1 +/- 1.4 min vs 20 +/- 11 min, P < 0.01) and total x-ray exposure (5.1 +/- 3.1 Gycm2 vs 24.9 +/- 1.6 Gycm2, P < 0.01). Isthmus geometry reconstruction could be performed in all patients of group II. In 4 patients (20%) of group II, anatomic isthmus variations were detected by NavX. No significant differences in radiofrequency current applications and procedural times were found between the two groups. CONCLUSION: NavX technology allows geometry reconstruction of the cavotricuspid isthmus. NavX-guided ablation of AFL reduces total x-ray exposure compared to the fluoroscopy-guided approach but does not prolong procedure time.     

Poststroke acute dysexecutive syndrome,a disorder resulting from minor stroke due to disruption of network dynamics

Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture–word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.

Advances in acute stroke treatment have significantly reduced motor and language deficits, converting highly morbid large hemispheric lesions into smaller infarcts with better overall long-term outcomes (1, 2). Prior work has shown that the majority of individuals presenting for follow-up 4- to 6-wk postinfarct now exhibit what would be classified as “minor symptoms,” (3) with low stroke severity measured by the NIH Stroke Scale (NIHSS) (4) and modified Rankin Scale (mRS) (5) scores. Although these individuals lack a dense hemiparesis or aphasia, over half endorse some degree of cognitive impairment that significantly impacts their recovery. Interestingly, these symptoms are typically found to be independent of stroke size, location, or coexisting depression (6, 7).Poststroke cognitive decline has a substantial presence in the literature (8–13). However, we find that rather than memory impairment or confusion, patients without prior cognitive disability report immediate difficulty with executive function, focus, concentration, and attention after a minor stroke, hereafter referred to as poststroke acute dysexecutive syndrome (PSADES) (3). Dysexecutive syndrome has been previously described in individuals with anatomic lesions (14) as well as disorders, such as schizophrenia (15) and Alzheimer’s disease (14), affecting the frontal lobes. When mild, the syndrome can be hard for others to appreciate, particularly, in previously high-functioning individuals, but poststroke, these deficits are detectable on screening tests, such as the Montreal cognitive assessment (MoCA) (16) and other scales of activities of daily living compared to age-matched controls (3). Despite the fact that following stroke, symptoms typically improve over the first 3–6 mo of recovery, PSADES impedes many successful well-educated individuals from returning to cognitively driven professions given the uncertainty of their prognosis. These decisions affect lifestyle and quality of life, resulting in lasting long-term consequences.The pathophysiology underlying PSADES is poorly understood, as many times the inciting infarct is small and does not involve an area of the brain classically thought to be important for cognitive processing. Cognitive change due to deep white matter lesions (in multiplicity) has been well described (17), but there is no clear unifying physiological explanation regarding how a single small cortical or subcortical lesion may cause significant generalized cortical dysfunction. Some posit a “network” hypothesis suggesting that an individual requires an extensive system of neuronal connectivity, involving numerous cortical and subcortical regions, in order to complete a task (18). We propose that the cognitive dysfunction of PSADES may be the result of a disruption of general network dynamics due to lesions of the subcortical white matter tracts, which would, in turn, interfere with basic network function.This study was designed as a first step in evaluating the role of network dynamics during tasks requiring attention, concentration, speed, and accuracy; all skills difficult for patients poststroke. We used magnetoencephalography (MEG) to determine the differences in cerebral activation patterns in nine individuals with small strokes versus a group of eight age-similar controls by measuring the amplitude and latency of cerebral responses during a visual comprehension task at two time points: ∼1- and 6-mo postinfarct. Our analysis focused on the early visual, M170, and M400 components of the event-related potential from the occipital lobe, fusiform gyrus, and lateral temporal lobe given their importance in visual recognition and language processing (19–22).