@article{AlnemerKotliarNeuhausetal.2023, author = {Alnemer, Momin Sami Mohammad and Kotliar, Konstantin and Neuhaus, Valentin and Pape, Hans-Christoph and Ciritsis, Bernhard D.}, title = {Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model}, series = {Cost Effectiveness and Resource Allocation}, journal = {Cost Effectiveness and Resource Allocation}, number = {21, Article number: 77}, publisher = {Springer Nature}, issn = {1478-7547}, doi = {10.1186/s12962-023-00482-4}, pages = {12 Seiten}, year = {2023}, abstract = {Background Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices. Methods This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare \& Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10\% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results. Results With a 10\% fracture risk reduction, model A costs between \$8,850 and \$46,940 per quality-adjusted life-year (\$/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8\% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side's prophylaxis, the patient's age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between \$11,000/QALY and \$74,000/QALY, which is below the defined willingness to pay threshold. Conclusion Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks.}, language = {en} } @article{KuchlerGuenthnerRibeiroetal.2023, author = {Kuchler, Timon and G{\"u}nthner, Roman and Ribeiro, Andrea and Hausinger, Renate and Streese, Lukas and W{\"o}hnl, Anna and Kesseler, Veronika and Negele, Johanna and Assali, Tarek and Carbajo-Lozoya, Javier and Lech, Maciej and Adorjan, Kristina and Stubbe, Hans Christian and Hanssen, Henner and Kotliar, Konstantin and Haller, Berhard and Heemann, Uwe and Schmaderer, Christoph}, title = {Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation}, volume = {26}, publisher = {Springer Nature}, address = {Dordrecht}, doi = {10.1007/s10456-023-09885-6}, pages = {547 -- 563}, year = {2023}, abstract = {Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42\% ± 1.77\% vs. 4.64\% ± 2.59\%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5-190.2] vs. 189.1 [179.4-197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8-0.9] vs. 0.88 [0.8-0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = - 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.}, language = {en} } @article{AngermannGuenthnerHanssenetal.2022, author = {Angermann, Susanne and G{\"u}nthner, Roman and Hanssen, Henner and Lorenz, Georg and Braunisch, Matthias C. and Steubl, Dominik and Matschkal, Julia and Kemmner, Stephan and Hausinger, Renate and Block, Zenonas and Haller, Bernhard and Heemann, Uwe and Kotliar, Konstantin and Grimmer, Timo and Schmaderer, Christoph}, title = {Cognitive impairment and microvascular function in end-stage renal disease}, series = {International Journal of Methods in Psychiatric Research (MPR)}, volume = {31}, journal = {International Journal of Methods in Psychiatric Research (MPR)}, number = {2}, publisher = {Wiley}, issn = {1049-8931 (Print)}, doi = {10.1002/mpr.1909}, pages = {1 -- 10}, year = {2022}, abstract = {Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.}, language = {en} } @article{KotliarOrtnerConradietal.2022, author = {Kotliar, Konstantin and Ortner, Marion and Conradi, Anna and Hacker, Patricia and Hauser, Christine and G{\"u}nthner, Roman and Moser, Michaela and Muggenthaler, Claudia and Diehl-Schmid, Janine and Priller, Josef and Schmaderer, Christoph and Grimmer, Timo}, title = {Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance}, series = {Neurobiology of Aging}, volume = {120}, journal = {Neurobiology of Aging}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0197-4580}, doi = {10.1016/j.neurobiolaging.2022.08.012}, pages = {117 -- 127}, year = {2022}, abstract = {Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.}, language = {en} } @article{WerfelGuenthnerHapfelmeieretal.2022, author = {Werfel, Stanislas and G{\"u}nthner, Roman and Hapfelmeier, Alexander and Hanssen, Henner and Kotliar, Konstantin and Heemann, Uwe and Schmaderer, Christoph}, title = {Identification of cardiovascular high-risk groups from dynamic retinal vessel signals using untargeted machine learning}, series = {Cardiovascular Research}, volume = {118}, journal = {Cardiovascular Research}, number = {2}, editor = {Guzik, Tomasz J.}, publisher = {Oxford University Press}, address = {Oxford}, issn = {0008-6363}, doi = {10.1093/cvr/cvab040}, pages = {612 -- 621}, year = {2022}, abstract = {Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.}, language = {en} } @article{AlbannaConzenWeissetal.2021, author = {Albanna, Walid and Conzen, Catharina and Weiss, Miriam and Seyfried, Katharina and Kotliar, Konstantin and Schmidt, Tobias Philip and Kuerten, David and Hescheler, J{\"u}rgen and Bruecken, Anne and Schmidt-Trucks{\"a}ss, Arno and Neumaier, Felix and Wiesmann, Martin and Clusmann, Hans and Schubert, Gerrit Alexander}, title = {Non-invasive assessment of neurovascular coupling after aneurysmal subarachnoid hemorrhage: a prospective observational trial using retinal vessel analysis}, series = {Frontiers in Neurology}, volume = {12}, journal = {Frontiers in Neurology}, number = {12}, issn = {1664-2295}, doi = {10.3389/fneur.2021.690183}, pages = {1 -- 15}, year = {2021}, abstract = {Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.}, language = {en} } @article{KuertenKotliarFuestetal.2021, author = {Kuerten, David and Kotliar, Konstantin and Fuest, Matthias and Walter, Peter and Hollstein, Muriel and Plange, Niklas}, title = {Does hemispheric vascular regulation differ significantly in glaucoma patients with altitudinal visual field asymmetry? A single-center, prospective study}, series = {International Ophthalmology}, volume = {41}, journal = {International Ophthalmology}, number = {41}, editor = {Neri, Piergiorgio}, publisher = {Springer}, address = {Berlin}, isbn = {1573-2630}, doi = {10.1007/s10792-021-01876-0}, pages = {3109 -- 3119}, year = {2021}, abstract = {Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.}, language = {en} } @incollection{Kotliar2021, author = {Kotliar, Konstantin}, title = {Ocular rigidity: clinical approach}, series = {Ocular Rigidity, Biomechanics and Hydrodynamics of the Eye}, booktitle = {Ocular Rigidity, Biomechanics and Hydrodynamics of the Eye}, editor = {Pallikaris, I. and Tsilimbaris, M. K. and Dastiridou, A. I.}, publisher = {Springer}, address = {Cham}, isbn = {978-3-030-64422-2}, doi = {10.1007/978-3-030-64422-2_2}, pages = {15 -- 43}, year = {2021}, abstract = {The term ocular rigidity is widely used in clinical ophthalmology. Generally it is assumed as a resistance of the whole eyeball to mechanical deformation and relates to biomechanical properties of the eye and its tissues. Basic principles and formulas for clinical tonometry, tonography and pulsatile ocular blood flow measurements are based on the concept of ocular rigidity. There is evidence for altered ocular rigidity in aging, in several eye diseases and after eye surgery. Unfortunately, there is no consensual view on ocular rigidity: it used to make a quite different sense for different people but still the same name. Foremost there is no clear consent between biomechanical engineers and ophthalmologists on the concept. Moreover ocular rigidity is occasionally characterized using various parameters with their different physical dimensions. In contrast to engineering approach, clinical approach to ocular rigidity claims to characterize the total mechanical response of the eyeball to its deformation without any detailed considerations on eye morphology or material properties of its tissues. Further to the previous chapter this section aims to describe clinical approach to ocular rigidity from the perspective of an engineer in an attempt to straighten out this concept, to show its advantages, disadvantages and various applications.}, language = {en} } @article{NeumaierWeissVeldemanetal.2021, author = {Neumaier, Felix and Weiss, Miriam and Veldeman, Michael and Kotliar, Konstantin and Wiesmann, Martin and Schulze-Steinen, Henna and H{\"o}llig, Anke and Clusmann, Hans and Schubert, Gerrit Alexander and Albanna, Walid}, title = {Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - preliminary findings from an observational cohort study}, series = {Clinical Neurology and Neurosurgery}, volume = {208}, journal = {Clinical Neurology and Neurosurgery}, number = {Article No.: 106870}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0303-8467}, doi = {10.1016/j.clineuro.2021.106870}, year = {2021}, abstract = {Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.}, language = {en} } @article{NeumaierKotliarHaerenetal.2021, author = {Neumaier, Felix and Kotliar, Konstantin and Haeren, Roel Hubert Louis and Temel, Yasin and L{\"u}ke, Jan Niklas and Seyam, Osama and Lindauer, Ute and Clusmann, Hans and Hescheler, J{\"u}rgen and Schubert, Gerrit Alexander and Schneider, Toni and Albanna, Walid}, title = {Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca v 2.3-Deficient Mice—An in- vivo Evaluation Using Retinal Vessel Analysis (RVA)}, series = {Frontiers in Neurology}, volume = {12}, journal = {Frontiers in Neurology}, publisher = {Frontiers}, doi = {10.3389/fneur.2021.659890}, pages = {1 -- 11}, year = {2021}, language = {en} }