Dragan Stojanov

Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status.

IntroductionGadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function.MethodsGadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits.ResultsRepeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear.ConclusionHere, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs.

The model for the end-stage liver disease and Child-Pugh score in predicting prognosis in patients with liver cirrhosis and esophageal variceal bleeding

BACKGROUND/AIM Esophageal variceal bleeding is one of the most frequent and gravest complications of liver cirrhosis, directly life-threatening. By monitoring certain clinical and laboratory hepatocellular insufficiency parameters (Child-Pugh score), it is possible to determine prognosis in patients who are bleeding and evaluate further therapy. Recently, the Model for the End-Stage Liver Disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. The aim of the study was to evaluate survival prognosis of cirrhotic patients by the MELD and Child-Pugh scores and to analyze the MELD score prognostic value in patients with both liver cirrhosis and variceal bleeding. METHODS We retrospectively evaluated the survival rate of a group of 100 cirrhotic patients of a median age of 57 years. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. We also analysed clinical and laboratory hepatocellular insufficiency parameters in order to examine their connection with a 15-month survival. The MELD values were correlated with the Child-Pugh scores. The Students t-test was used for statistical analysis. RESULTS Twenty-two patients died within 15-months followup. Age and gender did not affect survival rate. The Child-Pugh and MELD scores, as well as ascites and encephalopathy significantly differed between the patients who survived and those who died (p < 0.0001). The International Normalized Ratio (INR) values, serum creatinine and bilirubin were significantly higher, and albumin significantly lower in the patients who died (p < 0.0001). The MELD score was significantly higher in the group of patients who died due to esophageal variceal bleeding (p < 0.0001). CONCLUSION In cirrhotic patients the MELD score is an excellent survival predictor at least as well as the Child-Pugh score. Increase in the MELD score is associated with decrease in residual liver function. In the group of patients with liver cirrhosis and esophageal variceal bleeding, the MELD score identifies those with a higher intrahospital mortality risk.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common and best known monogenic small vessel disease. Here, we review the clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on the most relevant articles published between 1994 and 2016 and on the personal experience of the authors, all directly involved in CADASIL research and care. We conclude with some suggestions that may help in the clinical practice and management of these patients.

Reply to Letter to the Editor re: Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: Correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

We appreciate the interest and constructive comments expressed byBalzer et al. in their Letter to the Editor regarding our study BIncreasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance (MR) images in patients with relapsing-remitting multiple sclerosis (RRMS): Correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol^ [1], as well as the opportunity to respond to their concerns. As they correctly point out, our study was the first to provide evidence of a correlation between the use of a macrocyclic gadolinium-based contrast agent (GBCAs), gadobutrol and increased T1W magnetic resonance signal intensity (SI) in these regions in RRMS patients. While the experiments we described did not yield definitive evidence that use of macrocyclic GBCAs alone is responsible for the observed increases in SI, our study and others that have been published subsequently highlight the importance of further exploration of this phenomenon. The inclusion criteria in our study were selected to enable comparison to the results described by Kanda et al. [2], which was consistent with the design and interpretation of additional studies by Kanda et al. [3] and Radbrich et al. [4]. While this enhanced our ability to understand our results in context of those previous studies, it did contribute to some of the limitations of our study. We cannot exclude prior exposure to a GBCA before the first magnetic resonance (MR) images analysed in our department. Therefore, potential prolonged retention of the previous gadolinium application cannot be ruled out as a possible confounder. However, the relatively homogeneous patient groups in our study make this scenario highly unlikely. Furthermore, though it was not possible to compose a control group of non-CNS patients who received gadobutrol with brain MRI for this study, we did find elevation of SI after controlled applications of gadobutrol when compared to baseline values. The correlation we found was small, perhaps due to the relatively small number of patients included in the study. The SI changes we observed were also very small and sometimes difficult to see in images, even after a prolonged period of administration. Visual assessment of the presence or absence of hyperintensity on the T1WMR images is very subjective, hence the use of quantitative SI measurement after the first and last MRI examinations. We paid particular attention to using the same region size and location on both scans. Further research with a larger number of patients and longer periods of follow-up, along with evaluation based on autopsy specimens and/or animal experiments, is needed to confirm our results. Understanding the impact of other key factors, including disease progress and characteristics, is key to interpreting the role of repeated administration ofmacrocyclic GBCAs inmultiple sclerosis (MS) patients. We performed regular MR controls at each interval and disease activity did not influence the interval of contrast administration. This suggests that disease activity is not likely to explain the prominent effect in the group with the shortest period of contrast administrations. We believe this result is most probably a consequence of a higher contrast load and greater deposition of gadolinium over * Dragan A. Stojanov drstojanov@gmail.com

Breast MRI, digital mammography and breast tomosynthesis: comparison of three methods for early detection of breast cancer

Breast cancer is the most common malignancy in women and early detection is important for its successful treatment. The aim of this study was to investigate the sensitivity and specificity of three methods for early detection of breast cancer: breast magnetic resonance imaging (MRI), digital mammography, and breast tomosynthesis in comparison to histopathology, as well as to investigate the intraindividual variability between these modalities. We included 57 breast lesions, each detected by three diagnostic modalities: digital mammography, breast MRI, and breast tomosynthesis, and subsequently confirmed by histopathology. Breast Imaging-Reporting and Data System (BI-RADS) was used for characterizing the lesions. One experienced radiologist interpreted all three diagnostic modalities. Twenty-nine of the breast lesions were malignant while 28 were benign. The sensitivity for digital mammography, breast MRI, and breast tomosynthesis, was 72.4%, 93.1%, and 100%, respectively; while the specificity was 46.4%, 60.7%, and 75%, respectively. Receiver operating characteristics (ROC) curve analysis showed an overall diagnostic advantage of breast tomosynthesis over both breast MRI and digital mammography. The difference in performance between breast tomosynthesis and digital mammography was significant (p <0.001), while the difference between breast tomosynthesis and breast MRI was not significant (p=0.20).

Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks

In order to examine the endogenous antioxidants values in the earliest phase of demyelination, we have determined bilirubin and uric acid (UA) serum values in the patients with clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS), regarding their clinical disability, measured by Extended Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), disease duration, gender and other parameters. The bilirubin and UA levels were lower in CIS and RRMS patients than in control group, whether male or female (p < 0.05). The bilirubin and UA levels were decreased in RRMS compared to CIS patients (p < 0.05). Regarding EDSS, MRI and disease duration, obtained values of bilirubin and UA were higher in both study groups in patients with lower EDSS, lower MRI lesion number and shorter disease duration (p < 0.05). The greatest significance in decreased bilirubin and UA levels was observed in female compared to male patients, in both study groups (p < 0.05). The results suggest negative linear correlation between bilirubin and UA levels and disease duration, EDSS and MRI in CIS (p < 0.01), with the same correlation between bilirubin and UA levels and disease duration in RRMS patients (p < 0.01). There was also significant correlation between bilirubin level and MRI findings and UA levels and EDSS in RRMS patients (p < 0.01). The obtained results point to the importance of endogenous antioxidants in the outbreak and course of neuroinflammation. This could be favorable for the new pathogenetically conditioned neuroinflammatory therapy concepts which do not initially rely only on immunomodulatory, but also on the antioxidative effects.

The Role of Matrix Metalloproteinase 3 and 9 in the Pathogenesis of Acute Neuroinflammation. Implications for Disease Modifying Therapy.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in a variety of physiological and pathological processes, including those in CNS. In this study, plasma values of MMP-3 and MMP-9 have been compared in clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS) patients during their acute attacks, in relation to the biological activity of disease. Therefore, we compared the MMPs plasma values regarding Expanded Disability Status Scale (EDSS), progression index of disease (PID), acute brain lesion volume seen on magnetic resonance imaging (MRI) and index of blood-brain barrier (BBB) permeability destruction. The obtained results demonstrated higher plasma values of MMPs in both study groups than control values (p < 0.05). No statistical significances have been detected comparing the obtained values of both enzymes between CIS and RRMS group (p > 0.05). In both CIS and RRMS groups, the patients with higher EDSS showed higher MMPs plasma values (p < 0.05). The MMPs values were also significantly higher in both study patients with higher total number comparing to those with lower number of MRI brain lesion (p < 0.05) (beyond MMP-3 in RRMS). All obtained correlations, between MMPs and EDSS, PID, volume of MRI Gd-enhancement brain lesions, and index of BBB permeability, were positive (p < 0.05.) This study demonstrates alterations of both tested MMPs with closed correlation with the disease biological activity. Although MMPs are being implicated in the pathogenesis of acute neuroinflammation, the MMPs modulation might be useful in the future design of disease modifying therapy with the specific target profile.

Primary and salvage total laryngectomy. Influential factors, complications, and survival.

S hearing impaired people have intense problems especially when arriving in a public medical center, which must be considered with great prudence. Besides a propper arrangement of spatial arrays and organisational processes, there is a wide spectrum of interdisciplinary diagnostics, therapeutic approaches, rehabilitation offers and long term after care, which has to be included within a comprehensive center. The Wuerburg CHC was established in 2009 and gradually linked to all necessary partners including physicians, audiologists, psychologists, genetisists, radiologists as well as care attendants, medical engineers and health care professionals. Now the CHC offers the complete spectrum starting with newborn hearing screening, early hearing aid fitting and genetic counselling, including all kind of otosurgical procedures like classical middle ear surgery, cochlea and other hearing implants or acoustic neurinoma surgery and finally the necessary rehabilitation programs. Regular board meetings for difficult cases, new technological developments as well the integration of research programs enable a continuous adjustment to the rapidly developing field of hearing restoration. Patients feed back demonstrated, that the decoupling of the center from the general duty of a large university ENT clinic, succeeded in a better quality of patient care for hearing impaired people.C facial plastic surgery is based on achieving best possible results not only in correction of facial deformities but also in reconstruction of defects after tumor resection. It is not always an easy goal and sometimes it is necessary to perform multi stage surgical procedures to satisfy high aesthetic criteria of modern society. In corrective surgery of primary and secondary facial deformities, the most difficult task is to obtain natural look which will be socially accepted and will afford the patient normal life. Almost same criteria are in use when reconstructive surgery is in question. Doing this, at all times we have in our minds function, which should be unimpaired if not improved and aesthetic that will dominate in outside look and not interfere with function. These two main principles should be our ultimate goals in facial plastic and reconstructive surgery.D is a symptom observed in about half of the patients admitted to an acute clinic of geriatric medicine. Dysphagia can be caused by a multitude of illnesses and its consequences such as malnutrition, cachexia, dehydration and aspiration pneumonia are noted in a high percentage of geriatric in-patients. The male patient (80 years old) presented in this case study was admitted to our geriatric clinic because of a persistent cough and severe weight loss. He had had a 16 months long history of consultations at several hospitals and medical specialists: A bronchoscopy, an X-ray of the lungs and a laryngeal examination including stroboscopy at an ENT clinic had been conducted. Finally the patient had been diagnosed with a beginning fibrosis of the lungs and compulsive throat clearing. The latter was treated to little effect by a speech and language therapist. Bedside evaluation of the patient’s swallowing performance including the Daniels Test suggested severe dysphagia which was confirmed by a video endoscopic evaluation of swallowing. The endoscopy revealed great amounts of pharyngeal residues with a high risk of post deglutitive aspiration of pudding and silent aspiration of fluids. Further medical diagnostic procedure comprised a neurologic examination, an MRT of the brain stem and blood tests which suggested scleroderma as the underlying pathology. This was later confirmed by a clinic for entorology. Severe dysphagias caused by reduced opening of the upper esophagus sphincter and beginning fibrosis of the lungs were the first symptoms of scleroderma in this patient. In general, an examination of persistent cough should include screening for dysphagia and scleroderma should be considered as differential diagnosis.PURPOSE In this retrospective study we analysed patients with advanced squamous cell carcinoma of the larynx and hypopharynx treated with primary total laryngectomy (PTL) between 1990 and 2007. METHODS The patients were treated by classical PTL, radiotherapy 60-70 Gy, concomitant radio and chemotherapy (cisplatin and 5-fluorouracil) or salvage total laryngectomy (STL). They were followed up for 5 years and complications, survival, residual/recurrent disease and metastases were registered. RESULTS STL after previous radiotherapy (STL-pRT), and after chemoradiotherapy (STL-pCTRT) caused more frequent local complications than PTL. Five-year disease-free survival (DFS) rate was significantly influenced by TNM stage and localization of the primary laryngeal tumor. For laryngeal cancer it was: 61.3% for PTL, 54.1% for STL-pC-TRT, and 47.6% for STL-pRT. Incomplete responders to initial treatment had low survival rate. PTL for hypopharyngeal carcinoma and particularly salvage laryngectomy after chemoradiotherapy were associated with more frequent local complications. The 5-year DFS for hypopharyngeal cancer was lower than for laryngeal cancer. CONCLUSION PTL still offers the best survival rate with low complications for advanced laryngeal and hypopharyngeal squamous cell carcinoma. STL causes more frequent local complications, especially after chemoradiotherapy. Addition of chemotherapy to radiotherapy increases the survival. Five-year DFS rate depends on TNM stage and localization of the primary tumor.

Sensitivity and fading of pMOS dosemeters irradiated with X-ray radiation doses from 1 to 100 cGy

In this paper, the results of pMOS dosemeters sensitivity to X-ray radiation and 28-d fading at room temperature are presented. Two types of dosemeters were used, which differ in gate oxide layer thickness. The sensitivity of pMOS dosemeters with gate oxide layer thickness of 1 µm was followed in the dose intervals of 1 to 10 cGy and 10 to 100 cGy, whereas that of 400 nm was in the interval of 10 to 100 cGy. The sensitivity was characterised by the threshold voltage shift, which was determined as a function of absorbed radiation dose and time after irradiation. Linear dependence between threshold voltage shift and absorbed radiation dose was established, as well as that considerable fading occurs during the first few days after irradiation. The mechanisms responsible for threshold voltage shift during irradiation and latter annealing have been also discussed.

ADC is not reliable in determinating subtypes of meningiomas

ObjectiveTo verify the reliability of apparent diffusion coefficient (ADC) measurements in determining subtypes of meningiomas.Material and methodsThirty patients (20 women and 10 men; average age, 53±15 years) with meningiomas were prospectively studied using DWI with b values of 0 and 1000. ADC values of the neoplastic tissue were obtained as the mean of measurements from three regions of interests within the mass and compared with histologic subtypes using ANOVA test (SPSS16).ResultsThe meningothelial subtype was found in 15 (50%) patients, fibroblastic in 10 (33.33%) patients and cystic in 5 (16.67%) patients. All meningiomas belonged to the WHO Grade 1 — benign meningiomas. There was no significant statistical difference between meningothelial, fibroblastic and cystic meningiomas when considering mean ADC values (0.000411+/−0.000066 mm2/s vs. 0.000750+/−0.001045 mm2/s vs. 0.000688+/−0.000063 mm2/s (p>0.05). Perifocal edema was present only with fibroblastic meningioma with mean ADC 0.000683 mm2/s. The ADC of the cystic component was statistically significantly higher in cystic meningeomas (0.001283 mm2/s) compared with fibroblastic (0.000224 mm2/s) and meningothelial meningiomas (0.000088 mm2/s) (p<0.001). The ADC of meningiomas was higher compared with contralateral healthy brain tissue (0.000642 mm2/s vs. 0.000404 mm2/s; n.s).ConclusionADC measurement do not seem reliable in identifying histological subtypes of Grade I meningiomas.