Medical University of Graz

About: Medical University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Medicine. The organization has 5684 authors who have published 12349 publications receiving 417282 citations.

Is confocal microscopy a valuable tool in diagnosing nodular lesions? A study of 140 cases

Abstract: Background Nodular lesions pose diagnostic challenges because nodular melanoma may simulate all kinds of melanocytic and nonmelanocytic lesions. Reflectance confocal microscopy (RCM) is a novel technique that allows visualization of the skin at nearly histological resolution although limited laser depth penetration hampers visualization of the deep dermis. Objectives We sought to assess whether the diagnostic accuracy of RCM was comparable to histopathology for the diagnosis of nodular lesions, and to identify possible limitations of this technique. Methods We retrospectively evaluated 140 nodules by means of RCM while blinded from the histopathological diagnosis. At the end of the study the patient codes were broken and the evaluations were matched with histopathological diagnosis before performing statistical analysis. Results The study consisted of 140 nodular lesions (23 ‘pure’ nodular melanomas, nine melanoma metastases, 28 BCCs, six invasive SCCs, 32 naevi, 14 seborrhoeic keratoses, 17 dermatofibromas, five vascular lesions and six other lesions). RCM correctly diagnosed 121 of 140 lesions (864%); eight of 140 (57%) lesions revealed discordance between histopathology and confocal microscopy. Eight of the 140 (57%) cases were not evaluable by means of RCM due to the presence of ulceration or hyperkeratosis and three cases showed a nonspecific pattern. Interestingly, confocal microscopy reached a 965% sensitivity and 941% specificity (area under curve 0970) (95% CI 0924–1015) (P < 0001) for the diagnosis of melanoma. Conclusions The study is retrospective and lesions were not included on the basis of their diagnostic difficulty. Despite the limited laser depth penetration of RCM, this imaging tool represents an effective instrument in diagnosing nodular lesions; however, for fully ulcerated lesions or when a marked hyperkeratosis is present, biopsy should always be performed. Prospective studies on difficult-todiagnose nodules should be performed to analyse further the pros and cons of RCM in skin cancer diagnosis.

Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease.

Abstract: Objectives: We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease. Methods: We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs ( p Results: Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14–1.46, p = 0.00003; r 2 > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03–1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01–1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non–small vessel disease cerebrovascular phenotypes. Conclusions: Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.

Vitamin D and female fertility

Abstract: Purpose of reviewApart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes. We will review the most interesting and relevant studies on vitamin D an

First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors.

Abstract: Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and/or deleterious ATM mutations and received doses ≥40 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency. SIGNIFICANCE: Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population.See related commentary by Italiano, p. 14.This article is highlighted in the In This Issue feature, p. 1.

Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis

Abstract: Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally Improved accuracy and sensitivity will reduce the numbers of patients required to detect a given treatment effect in a trial, and ultimately, will allow reliable characterization of individual patients for personalized treatment Based on open issues in the field of MS research, and the current state of the art in magnetic resonance image analysis methods for assessing brain lesion load and atrophy, this paper makes recommendations to improve these measures for longitudinal studies of MS Briefly, they are (1) images should be acquired using 3D pulse sequences, with near-isotropic spatial resolution and multiple image contrasts to allow more comprehensive analyses of lesion load and atrophy, across timepoints Image artifacts need special attention given their effects on image analysis results (2) Automated image segmentation methods integrating the assessment of lesion load and atrophy are desirable (3) A standard dataset with benchmark results should be set up to facilitate development, calibration, and objective evaluation of image analysis methods for MS