Publications by authors named "Darius Kalasauskas"

13 Publications

  • Page 1 of 1

Psychological Burden in Meningioma Patients under a Wait-and-Watch Strategy and after Complete Resection Is High-Results of a Prospective Single Center Study.

Cancers (Basel) 2020 Nov 25;12(12). Epub 2020 Nov 25.

Department of Neurosurgery, University Medical Centre, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.

The diagnosis of intracranial meningiomas as incidental findings is increasing by growing availability of MRI diagnostics. However, the psychological distress of patients with incidental meningiomas under a wait-and-watch strategy is unknown. Therefore, we aimed to compare the psychosocial situation of meningioma patients under wait-and-watch to patients after complete resection to bridge this gap. The inclusion criteria for the prospective monocenter study were either an incidental meningioma under a wait-and-watch strategy or no neurologic deficits after complete resection. Sociodemographic, clinical, and health-related quality of life and clinical data were assessed. Psychosocial factors were measured by the Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), and the Short Form (SF-36). A total of 62 patients were included (n = 51 female, mean age 61 (SD 13) years). According to HADS, the prevalence of anxiety was 45% in the postoperative and 42% in the wait-and-watch group ( = 0.60), and depression was 61% and 87%, respectively ( = 0.005). In total, 43% of patients under wait-and-watch and 37% of patients in the postoperative group scored ≥6 on the DT scale. SF-36 scores were similar in all categories except general health ( = 0.005) and physical component aggregate score (43.7 (13.6) vs. 50.5 (9.5), ( = 0.03), both lower in the wait-and-watch group. Multivariate analysis revealed the wait-and-watch strategy was associated with a 4.26-fold higher risk of a pathological depression score based on HADS ( = 0.03). This study demonstrates a high prevalence of psychological distress in meningioma patients. Further evaluation is necessary to identify the patients in need of psychooncological support.
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http://dx.doi.org/10.3390/cancers12123503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761113PMC
November 2020

High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage.

PLoS One 2020 11;15(11):e0241565. Epub 2020 Nov 11.

Department of Neurosurgery, University Medical Center Mainz, Mainz, Germany.

Background: The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome.

Methods: Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH.

Results: Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r2 = 0.73; < 0.005) and 6 months (r2 = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r2 = 0.54; < 0.01) and 6 months (r2 = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01).

Conclusion: In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241565PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657554PMC
December 2020

Identification of High-Risk Atypical Meningiomas According to Semantic and Radiomic Features.

Cancers (Basel) 2020 Oct 12;12(10). Epub 2020 Oct 12.

Department of Neurosurgery, University Medical Centre, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.

Up to 60% of atypical meningiomas (World Health Organization (WHO) grade II) reoccur within 5 years after resection. However, no clear radiological criteria exist to identify tumors with higher risk of relapse. In this study, we aimed to assess the association of certain radiomic and semantic features of atypical meningiomas in MRI with tumor recurrence. We identified patients operated on primary atypical meningiomas in our department from 2007 to 2017. An analysis of 13 quantitatively defined radiomic and 11 qualitatively defined semantic criteria was performed based on preoperative MRI scans. Imaging characteristics were assessed along with clinical and survival data. The analysis included 76 patients (59% women, mean age 59 years). Complete tumor resection was achieved in 65 (86%) cases, and tumor relapse occurred in 17 (22%) cases. Mean follow-up time was 41.6 (range 3-168) months. Cystic component was significantly associated with tumor recurrence (odds ratio (OR) 21.7, 95% confidence interval (CI) 3.8-124.5) and shorter progression-free survival (33.2 vs. 80.7 months, < 0.001), whereas radiomic characteristics had no predictive value in univariate analysis. However, multivariate analysis demonstrated significant predictive value of high cluster prominence (hazard ratio (HR) 5.89 (1.03-33.73) and cystic component (HR 20.21 (2.46-166.02)) for tumor recurrence. The combination of radiomic and semantic features might be an effective tool for identifying patients with high-risk atypical meningiomas. The presence of a cystic component in these tumors is associated with a high risk of tumor recurrence.
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http://dx.doi.org/10.3390/cancers12102942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599676PMC
October 2020

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.

J Neurosurg 2020 06 12:1-8. Epub 2020 Jun 12.

1Department of Neurosurgery and Machine Intelligence in Clinical Neuroscience (MICN) Laboratory, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland.

Objective: Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impairment.

Methods: The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated.

Results: In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/.

Conclusions: Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.
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http://dx.doi.org/10.3171/2020.4.JNS20643DOI Listing
June 2020

Diversity of Clinically Relevant Outcomes Resulting from Hypofractionated Radiation in Human Glioma Stem Cells Mirrors Distinct Patterns of Transcriptomic Changes.

Cancers (Basel) 2020 Mar 1;12(3). Epub 2020 Mar 1.

Laboratory for Experimental Neurooncology, Clinic for Neurosurgery, Johannes Gutenberg University Medical Centre, 55131 Mainz, Germany.

Hypofractionated radiotherapy is the mainstay of the current treatment for glioblastoma. However, the efficacy of radiotherapy is hindered by the high degree of radioresistance associated with glioma stem cells comprising a heterogeneous compartment of cell lineages differing in their phenotypic characteristics, molecular signatures, and biological responses to external signals. Reconstruction of radiation responses in glioma stem cells is necessary for understanding the biological and molecular determinants of glioblastoma radioresistance. To date, there is a paucity of information on the longitudinal outcomes of hypofractionated radiation in glioma stem cells. This study addresses long-term outcomes of hypofractionated radiation in human glioma stem cells by using a combinatorial approach integrating parallel assessments of the tumor-propagating capacity, stemness-associated properties, and array-based profiling of gene expression. The study reveals a broad spectrum of changes in the tumor-propagating capacity of glioma stem cells after radiation and finds association with proliferative changes at the onset of differentiation. Evidence is provided that parallel transcriptomic patterns and a cumulative impact of pathways involved in the regulation of apoptosis, neural differentiation, and cell proliferation underly similarities in tumorigenicity changes after radiation.
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http://dx.doi.org/10.3390/cancers12030570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139840PMC
March 2020

Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Glioblastoma.

Cancers (Basel) 2020 Feb 24;12(2). Epub 2020 Feb 24.

Institute of Personalized Medicine, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

Inevitable recurrence after radiochemotherapy is the major problem in the treatment of glioblastoma, the most prevalent type of adult brain malignancy. Glioblastomas are notorious for a high degree of intratumor heterogeneity manifest through a diversity of cell types and molecular patterns. The current paradigm of understanding glioblastoma recurrence is that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate that therapy-driven molecular evolution is a fundamental trait associated with glioblastoma recurrence. There is a growing body of evidence indicating that intratumor heterogeneity, longitudinal changes in molecular biomarkers and specific impacts of glioma stem cells need to be taken into consideration in order to increase the accuracy of molecular diagnostics still relying on readouts obtained from a single tumor specimen. : This study integrates a multisampling strategy, longitudinal approach and complementary transcriptomic investigations in order to identify transcriptomic traits of recurrent glioblastoma in whole-tissue specimens of glioblastoma or glioblastoma stem cells. In this study, 128 tissue samples of 44 tumors including 23 first diagnosed, 19 recurrent and 2 secondary recurrent glioblastomas were analyzed along with 27 primary cultures of glioblastoma stem cells by RNA sequencing. A novel algorithm was used to quantify longitudinal changes in pathway activities and model efficacy of anti-cancer drugs based on gene expression data. : Our study reveals that intratumor heterogeneity of gene expression patterns is a fundamental characteristic of not only newly diagnosed but also recurrent glioblastomas. Evidence is provided that glioblastoma stem cells recapitulate intratumor heterogeneity, longitudinal transcriptomic changes and drug sensitivity patterns associated with the state of recurrence. : Our results provide a transcriptional rationale for the lack of significant therapeutic benefit from temozolomide in patients with recurrent glioblastoma. Our findings imply that the spectrum of potentially effective drugs is likely to differ between newly diagnosed and recurrent glioblastomas and underscore the merits of glioblastoma stem cells as prognostic models for identifying alternative drugs and predicting drug response in recurrent glioblastoma. With the majority of recurrent glioblastomas being inoperable, glioblastoma stem cell models provide the means of compensating for the limited availability of recurrent glioblastoma specimens.
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http://dx.doi.org/10.3390/cancers12020520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072286PMC
February 2020

Impact of postoperative radiotherapy on recurrence of primary intracranial atypical meningiomas.

J Neurooncol 2020 Jan 3;146(2):347-355. Epub 2020 Jan 3.

Department of Neurosurgery, University Medical Center Mainz, Johannes Gutenberg University of Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Background: Atypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas.

Methods: The medical records of all patients who underwent surgery (2007-2017 in 4 neurosurgical departments) for a histologically diagnosed primary atypical meningioma were reviewed to assess progression-free survival (PFS) and prognostic factors.

Results: This analysis included 258 patients with a median age of 60 years (54.7% female). The predominant tumor locations were convexity and falx (60.9%) followed by the skull base (37.2%). Simpson grade I-II resection was achieved in 194 (75.2%) patients, Simpson grade III-IV in 53 patients (20.5%). Tumor progressed in 54 cases (20.9%). Postoperative RT was performed in 46 cases (17.8%). RT was more often applied after incomplete resection (37.7% vs. 13.4% Simpson III-IV vs. I-II). A multivariate analysis showed a significantly shorter PFS associated with Simpson III-IV [HR 1.19, (95% CI) 1.09-1.29, p < 0.001] and age > 65 years [HR 2.89, (95% CI) 1.56-5.33, p = 0.001]. A subgroup analysis with a minimal follow-up of 36 months revealed that Simpson III-IV [HR 3.01, 95% CI 1.31-6.931.03-1.24, p = 0.009] and age > 65 years [HR 2.48, 95% CI 1.20-5.13, p = 0.014] reduced PFS. The impact of postoperative RT on PFS remained statistically insignificant, even in a propensity-score matched survival analysis [n = 46; p = 0.438; OR 0.710 (0.299-1.687)].

Conclusions: In the present study, postoperative RT did not improve PFS. The most important prognostic factors remain the extent of resection and age.
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http://dx.doi.org/10.1007/s11060-019-03382-xDOI Listing
January 2020

Amphotericin B Penetrates into the Central Nervous System Through Focal Disruption of the Blood Brain Barrier in Experimental Hematogenous Meningoencephalitis.

Antimicrob Agents Chemother 2019 Oct 7. Epub 2019 Oct 7.

Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY, USA.

Hematogenous meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeability and low cerebrospinal fluid (CSF) concentrations, but is effective in treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions. An BBB model was serially infected with Liposomal AmB (LAMB) or deoxycholate AmB (DAMB) at 5 μg/ml were then provided, vascular and CNS compartments were sampled 4h later. For correlation, rabbits with experimental HCME received a single dose of DAMB 1 mg/kg or LAMB 5 mg/kg, and were euthanized after 1, 3, 6 and 24h. Evans blue solution (2%) 2 ml/kg administered IV one hour prior to euthanasia stained infected regions of tissue but not histologically normal areas. AmB concentrations in stained and unstained tissue regions were measured using UPLC. For selected rabbits, MRI scans performed on days 1-7 postinoculation were acquired before and after IV bolus Gd-DTPA at 15min intervals through 2h post-injection. The greatest degree of penetration of DAMB and LAMB through the BBB occurred after 24h of exposure (=0.0022). the concentrations of LAMB and DAMB in brain abscesses were 4.35±0.59 and 3.14±0.89-times higher vs. normal tissue (≤0.019). MRI scans demonstrated that Gd-DTPA accumulated in infected areas with disrupted BBB. Localized BBB disruption in HCME allows high concentrations of AmB within infected tissues, despite the presence of low CSF concentrations.
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http://dx.doi.org/10.1128/AAC.01626-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879260PMC
October 2019

Bone Flap Necrosis due to Low Grade Infection with Propionibacterium Acnes.

World Neurosurg 2018 Dec 24. Epub 2018 Dec 24.

Department of Neurological Surgery, University Medical Center Mainz, Germany.

Osteonecrosis of bone flaps after cranioplasty with autologeous cryo-conserved bone flaps is a common phenomenon. The exact reason for it remains unknown. We present a case of a 67-year old patient who had a bone flap necrosis after elective craniotomy and underwent secondary cranioplasty. A low-grade infection with Propionibacterium acnes was detected in microbiological samples from the bone flap as cause of the lysis. We discuss similarities with aseptic implant loosening and present recent evidence that low-grade infections might be the underlying reason in several cases. We conclude that low-grade infections play an underestimated role in bone flap necrosis after cranioplasty as well and encourage routine microbiological sampling (extended culture and PCR) to rule out infection in all similar cases and suggest a routine antibiotic therapy until final microbiological results.
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http://dx.doi.org/10.1016/j.wneu.2018.12.055DOI Listing
December 2018

Fungal Infections of the Central Nervous System in Children.

J Pediatric Infect Dis Soc 2017 Sep;6(3):e123-e133

Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York.

Although uncommon in children, fungal infections of the central nervous system can be devastating and difficult to treat. A better understanding of basic mycologic, immunologic, and pharmacologic processes has led to important advances in the diagnosis and management of these diseases, but their mortality rates remain unacceptably high. In this focused review, we examine the epidemiology and clinical features of the most common fungal pathogens of the central nervous system in children and explore recent advances in diagnosis and antifungal therapy.
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http://dx.doi.org/10.1093/jpids/pix059DOI Listing
September 2017

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

J Neurooncol 2016 May 30;127(3):473-82. Epub 2016 Jan 30.

University Medical Centre, Johannes Gutenberg-University, Langenbeckstraße 1, 55101, Mainz, Germany.

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.
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http://dx.doi.org/10.1007/s11060-016-2062-8DOI Listing
May 2016

Continuous-wave near-infrared spectroscopy is not related to brain tissue oxygen tension.

J Clin Monit Comput 2016 Oct 20;30(5):641-7. Epub 2015 Aug 20.

Department of Neurosurgery, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany.

Near-infrared spectroscopy (NIRS) has gained acceptance for cerebral monitoring, especially during cardiac surgery, though there are few data showing its validity. We therefore aimed to correlate invasive brain tissue oxygen measurements (PtiO2) with the corresponding NIRS-values (regional oxygen saturation, rSO2). We also studied whether NIRS was able to detect ischemic events, defined as a PtiO2-value of <15 mmHg. Eleven patients were studied with invasive brain tissue oxygen monitoring and continuous-wave NIRS. PtiO2-correlation with corresponding NIRS-values was calculated. We found no correlation between PtiO2- and NIRS-readings. Measurement of rSO2 was no better than flipping a coin in the detection of cerebral ischemia when a commonly agreed ischemic PtiO2 cut-off value of <15 mmHg was chosen. Continuous-wave-NIRS was unable to reliably detect ischemic cerebral episodes, defined as a PtiO2 value <15 mmHg. Displayed NIRS-values did not correlate with invasively measured PtiO2-values. CW-NIRS should not be used for the detection of cerebral ischemia.
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http://dx.doi.org/10.1007/s10877-015-9755-yDOI Listing
October 2016

Trends and social differences in alcohol consumption during the postcommunist transition in Lithuania.

ScientificWorldJournal 2012 29;2012:615183. Epub 2012 Apr 29.

Health Research Institute, Faculty of Public Health, Academy of Medicine, Lithuanian University of Health Sciences, 50009 Kaunas, Lithuania.

The aim of the study was to evaluate the trends and social differences in consumption of various types of alcoholic beverages in Lithuania over the postcommunist transition period (1994-2010). The data were obtained from nine nationally representative postal surveys of Lithuanian population aged 20-64 conducted every second year (n = 17154). Prevalence of regular (at least once a week) consumption of beer, wine, or strong alcoholic beverages and the amount of alcohol consumed per week were examined. Regular beer drinking as well as the amounts consumed increased considerably in both genders. The increase in regular consumption of strong alcohol was found among women. Sociodemographic patterning of regular alcohol drinking was more evident in women than in men. In women, young age and high education were associated with frequent regular drinking of wine and beer. Social differences in regular alcohol drinking should be considered in further development of national alcohol control policy in Lithuania.
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http://dx.doi.org/10.1100/2012/615183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353497PMC
October 2012