# University of Ostrava

• Ostrava, Ostrava, Czechia
Recent publications
Background: Serum neurofilaments (sNfs), especially the most investigated serum neurofilament light chain (sNfL), are promising biomarkers in multiple sclerosis (MS). However, their clinical utility is still limited, given the availability and costs of accessible analytical methods. The gold standard for the detection of sNfs is represented by the single molecule arrays (SIMOA). Recently, a high sensitivity enzyme-linked immunosorbent assay (hsELISA) has also been introduced. The objective of the study was to compare both assays for the determination of sNfL and neurofilament heavy chain (sNfH) concentrations in a defined MS cohort. The second objective was to identify contributing factors to sNfs concentrations determined by hsELISA. Methods: Serum samples were collected from MS patients attending the MS Centre, University Hospital Ostrava, Czech Republic. The levels of sNfs were detected using SIMOA and hsELISA assays. Results: The Spearman’s rank correlation coefficient between the sNfL SIMOA and sNfL hsELISA and between the sNfH SIMOA and sNfH hsELISA was moderate rs= 0.543 (p = 0.001) and rs= 0.583 (p = 0.001), respectively. The Passing-Bablok regression analysis demonstrated bias between both methods. Equally significant bias between the methods was confirmed by the Bland-Altman plots. Furthermore, confounding factors affecting the sNfL levels were glomerular filtration rate (eGFR; 95% CI -2.34 to -0.04) and sex (95% CI -2.38 to -0.10). The sNfH levels were affected by age (95% CI 0.01 to 0.07), eGFR (95% CI -2.45 to -0.02), body mass index (BMI; 95% CI -0.31 to -0.05), and blood volume (95% CI 0.69 to 3.35). Conclusion: This analytical study showed significant differences between hsELISA and SIMOA methods, especially for the sNfH concentrations. We identified confounding factors for sNfs levels determined by hsELISA. The sNfs levels were influenced by renal function and sex, whilst sNfH levels were affected by age, BMI, and total blood volume.
The COVID-19 pandemic is still ravaging the planet, but its (short-, medium-, and long-term) diverse effects on health, economy, and society are far from being understood. This article investigates the potential impact of a deadly epidemic and its main nonpharmaceutical control interventions (social distancing vs. testing-tracing-isolation, TTI) on capital accumulation and economic development at different time scales. This is done by integrating an epidemiological susceptible-infectious-recovered model with a Solow-type growth model including public expenditure, as a parsimonious setting to offer insights on the trade-off between protecting human lives and the economy and society. The work clarifies (i) the long-term interactions amongst a deadly infection, demography, and capital accumulation, (ii) the lack of viability of persistent social distancing measures also using an analytical characterization, and the threat of policy-enhanced COVID-19 endemicity, (iii) the potentially high return on investments in TTI activities to avoid future lockdowns and related capital disruption. It also quantifies the welfare effects of a range of policies, confirming a counterintuitive role for tax-funded preventive investments aimed at strengthening TTI as more desirable interventions than generalized lockdowns.
Context: Achieving minimal residual disease negativity (MRD-) in MM is associated with improved survival. Isatuximab (Isa) plus carfilzomib (K) and dexamethasone (d) is approved for relapsed MM patients after ≥1 prior therapy, based on IKEMA interim analysis (NCT03275285). Objective: Report updated, longer-term depth of response (DoR) results from IKEMA, including MRD-status. Design and patients: IKEMA, a randomized, open-label, multicenter Phase 3 study, investigates Isa-Kd (n=179) versus Kd (n=123) in relapsed MM patients with 1-3 prior lines of therapy. Interventions: IV Isa 10 mg/kg was given QW for 4 weeks, followed by Q2W. Both arms received an approved schedule of K (IV) and d (oral/IV). Main outcome measures: This prespecified analysis evaluated PFS (primary endpoint) at 159 events; secondary endpoints were ≥CR (+stringent CR), MRD-, and ≥CR+MRD-rates, as determined by IRC based on central laboratory data and review of local radiology. MRD status was assessed by NGS (sensitivity threshold ≥10-5) in bone marrow aspirates from patients achieving ≥VGPR. HYDRASHIFT Isa immunofixation (IFE) test, removing Isa interference in IFE, was used to update ≥CR rate. Secondary endpoints were compared between treatment arms using Cochran-Mantel-Haenszel test. One-sided descriptive P-values were provided. All randomized patients not reaching MRD- or without MRD assessment were considered MRD+. Results: At cutoff (14-Jan-2022), with a median follow-up of 44 months, deeper responses were observed in Isa-Kd versus Kd, ≥CR rates 44.1% versus 28.5% (OR: 2.09; 95%CI=1.26-3.48; descriptive P=0.0021). For Isa-Kd versus Kd patients, MRD- (10-5) occurred in 33.5% versus 15.4% (OR: 2.78; 95%CI=1.55-4.99; descriptive P=0.0002), with 26.3% versus 12.2% reaching ≥CR+MRD- (10-5; OR: 2.57; 95%CI=1.35-4.88; P=0.0015); MRD- at 10-6 sensitivity occurred in 10.6% versus 3.3%. MRD- versus MRD+ patients (10-5) had longer mPFS (months); Isa-Kd: not calculable ([NC]; 95%CI=NC-NC) versus 21.7 (95%CI=16.4-27.1); Kd: NC (95%CI=29.2-NC) versus 16.2 (95%CI=13.4-19.5). Conclusions: These results demonstrate clinically meaningful improvement in DoR with Isa-Kd versus Kd. Impressive ≥CR and ≥CR+MRD- (10-5) rates in Isa-Kd versus Kd are the highest reported for proteasome inhibitor-based regimens in relapsed MM. Achieving MRD- led to better outcomes in both arms; Isa-Kd patients had >2-fold higher likelihood of achieving MRD-. Additionally, Isa improved outcomes of MRD+ patients.
Context: Anti-CD38 antibody Isa in combination with Kd is approved in various countries for relapsed multiple myeloma (MM) patients after ≥1 prior therapy based on primary interim analysis (IA) of the Phase 3 IKEMA study (NCT03275285). Objective: To report updated efficacy and safety results from IKEMA. Setting and Main Outcome Measures: This prespecified analysis (179 patients randomized to Isa-Kd, 123 to Kd) evaluated progression-free survival (PFS) (primary endpoint) at 159 PFS events, PFS2, minimal residual disease negativity (MRD-) rate, complete response (CR) rate, MRD- and CR rates in all patients, and safety. Interventions: Isa 10 mg/kg was given IV weekly for 4 weeks and then every 2 weeks; Kd (20/56 mg/m2, twice weekly, 3/4 weeks) was administered in both arms. Results: At cutoff (14-Jan-2022), with a 44-month median follow-up, 49 (27.4%) patients in Isa-Kd and 11 (8.9%) in Kd were still on treatment. Updated PFS, consistent with IA results, demonstrated significant benefit in favor of Isa-Kd (vs. Kd): HR=0.58 (95.4%CI=0.42-0.79; 35.7 vs. 19.2 months); PFS2 HR=0.68 (95%CI=0.50-0.94; 47.2 vs. 35.6 months). Primary PFS analysis, per FDA request/sensitivity analysis for other countries (censoring PFS events occurring >8 weeks after last valid assessment), was 41.7 versus 20.8 months (HR=0.59, 95%CI=0.42-0.83). With additional follow-up and using Hydrashift Isa immunofixation assay to rule out potential Isa interference in CR determination, final CR rate (Isa-Kd vs. Kd) was 44.1% versus 28.5% (OR=2.09, 95%CI=1.26-3.48); ORR was 86.6% versus 83.7%; MRD- was reached in 33.5% versus 15.4% patients (OR=2.78, 95%CI=1.55-4.99); and the rate of MRD- CR patients was 26.3% versus 12.2% (OR=2.57, 95%CI=1.35-4.88). Safety profiles in both arms remain consistent with prior IKEMA findings. Serious TEAEs were reported in 70.1% of Isa-Kd versus 59.8% Kd patients. The most common any-grade non-hematologic TEAEs in Isa-Kd were infusion reaction (45.8%), diarrhea (39.5%), hypertension (37.9%), and upper respiratory tract infection (37.3%). Conclusions: These results show unprecedented mPFS, CR, MRD-, and MRD- CR rates in non-lenalidomide containing regimens with benefits maintained through subsequent therapies and a manageable safety profile. Moreover, PFS analysis using FDA censoring rules showed consistent results with the IA. Our findings support Isa-Kd as a standard-of-care treatment for relapsed MM patients.
This study was aimed to analyse the lower limb kinematics during the change of direction (COD) performance with the dominant (DL) and non-dominant (NDL) leg using linear (traditional kinematics) and nonlinear (Self Organising Map-based cluster analysis) approaches. Three 5-0-5 COD performances with the DL and three with the NDL were performed by 23 (aged 21.6 ± 2.3 years) collegiate athletes. No significant difference was observed between the COD duration, and approach speed of DL and NDL. Significantly greater ankle abductions, knee and hip external rotations were identified in COD with DL, compared to NDL (p < .001, d > 0.8). Self Organising Maps portrayed a completely different coordination pattern profile during change of direction performance with the DL and NDL. The cluster analysis illustrated similar inter-individual coordination patterning when participants turned with their DL or NDL. No visible relationship was observed in the cluster analysis of the lower limb joint angles and angular velocities. Outcomes of this study portrayed that coordination patterning (combination of joint angles and the rate of change of angles) could portray the movement patterning differences in different tasks, while a sole investigation on the joint angles or angular velocities may not reveal the underlying mechanisms of movement patterning.
Background Peroral endoscopic myotomy (POEM) is nowadays a standard method for treatment of achalasia; nevertheless, it remains an invasive intervention with corresponding risk of adverse events (AEs). The classification and grading of AEs are still a matter of discussion. The aim of our retrospective study was to assess the occurrence of all “undesirable” events and “true” adverse events in patients undergoing POEM and to compare the outcomes when either Clavien–Dindo classification (CDC) or American Society of Gastrointestinal Endoscopy (ASGE) lexicon classification applied. Methods This was a retrospective analysis of prospectively managed database of all patients who had undergone POEM between December 2012 and August 2018. We assessed the pre-, peri-, and early-postoperative (up to patient’s discharge) undesirable events (including those not fulfilling criteria for AEs) and “true” AEs according the definition in either of the classifications. Results A total of 231 patients have successfully undergone 244 POEM procedures (13 × re-POEM). Twenty-nine procedures (11.9%) passed uneventfully, while in 215 procedures (88.1%), a total of 440 undesirable events occurred. The CDC identified 27 AEs (17 minor, 10 major) occurring in 23/244 (9.4%) procedures. The ASGE lexicon identified identical 27 AEs (21 mild or moderate, 6 severe or fatal) resulting in the severity distribution of AEs being the only difference between the two classifications. Only the absence of previous treatment was found to be a risk factor [p = 0.047, OR with 95% CI: 4.55 (1.02; 20.25)] in the combined logistic regression model. Conclusion Undesirable events are common in patients undergoing POEM but the incidence of true AEs is low according to both classifications. Severe adverse events are infrequent irrespective of the classification applied. CDC may be more appropriate than ASGE lexicon for classifying POEM-related AEs given a surgical nature of this procedure. Graphical abstract
Obesity is a serious metabolic disease that significantly increases cardiovascular risks and other health complications. Sarcopenia is an independent risk factor for morbidity and mortality in patients suffering from obesity that increases the health risks and is associated with cardiac, respiratory and other diseases. Bariatric and metabolic surgery (BMS) leads to significant changes in body composition. Our pilot study showed that bariatric patients are at risk of sarcopenia after BMS. This finding resulted in a hypothesis that an exercise plan in the experimental group will lead to postural stabilization and a lower decline in muscle homotopy, further leading to a greater reduction in fat mass and a positive effect of exercise on skeletal muscle volume and strength and endocrine-metabolic function. The aim of the present study is to determine the effect of programmed aerobic and strength training on muscle function, volume, and morphology in patients after BMS. The study is a single-center, randomized clinical trial after sleeve gastrectomy focused on muscle tissue. The experimental group will perform targeted physical activity once a week for 12 months and the training plan will include anaerobic and aerobic components. Magnetic resonance imaging of skeletal muscles will be correlated with the values of densitometry examination and changes in body composition, certain blood parameters of myokines, biomechanical analysis of movement abnormalities, and behavioral and dietary counseling. This study will address the research questions about the effect of programmed training on muscle tissue and muscular functions after BMS.
De facto states need external support to advance their national interests. Many of them depend on their patron’s assistance, thus becoming their clients. In turn, patronless de facto states derive certain benefits from engaging with various external actors. This study proposes including a new category of actors in this group, namely quasi-patrons, whose relations with de facto states resemble the patron—client relationship. This means that patronless de facto states can enjoy greater external support than the literature suggests. To illustrate the relationship between client de facto states and quasi-patrons, the case of Somaliland and Ethiopia is explored.
The protection of metal parts against corrosion damage is one of the most comprehensive areas of industrial chemistry and a wide range of methods exists to protect the surface from corrosive stimulators, including phosphating. A key phosphating process, the tricationic phosphating, consists of baths containing zinc dihydrogen phosphate and other cations, such as Zn ²⁺ , Co ²⁺ , Ni ²⁺ or Mg ²⁺ . However, cobalt and nickel ions are classified as environmentally harmful and they are being actively excluded from industrial processes. The use of sufficiently micronized zinc phosphate dihydrate (µ-Zn 3 (PO 2 ) 2 · 2H 2 O) is one the possible approaches to significantly reduce or eliminate heavy metals from the phosphating process. The micronized zinc phosphate dihydrate serves as a nucleus on the metal surface to form a sufficiently high-quality phosphate layer. The study aims to find a procedurally optimal dispersion methodology suitable for application in the Czech Republic. The use of progressive grinding methods such as the jet mills is emphasized and shows promising results.
We prove that for any non-degenerate dendrite D , there exist topologically mixing maps $F : D \to D$ and $f : [0, 1] \to [0, 1]$ such that the natural extensions (as known as shift homeomorphisms) $\sigma _F$ and $\sigma _f$ are conjugate, and consequently the corresponding inverse limits are homeomorphic. Moreover, the map f does not depend on the dendrite D and can be selected so that the inverse limit $\underleftarrow {\lim } (D,F)$ is homeomorphic to the pseudo-arc. The result extends to any finite number of dendrites. Our work is motivated by, but independent of, the recent result of the first and third author on conjugation of Lozi and Hénon maps to natural extensions of dendrite maps.
H I G H L I G H T S Breast stiffness severely affects clinical-and self-examination of the breast. Development of subjective stiffness scale based on expert examination. Objective stratification based on interval of increment of strain energy density. Proposed scale correlates with subjective clinical examination in 92%. Women with stiff breasts may benefit from frequent checkup procedures. A B S T R A C T Breast cancer is diagnosed through a patient's Breast Self-Examination (BSE), Clinical Breast Examination (CBE), or para-clinical methods. False negativity of PCM in breast cancer diagnostics leads to a persisting problem associated with breast tumors diagnosed only in advanced stages. As the tumor volume/size at which it becomes inva-sive is not clear, BSE and CBE play an exceedingly important role in the early diagnosis of breast cancer. The quality and effectiveness of BSE and CBE depend on several factors, among which breast stiffness is the most important one. In this study, the authors present four methods for evaluating breast stiffness pathology during mammography examination based on the outputs obtained during the breast compression process, id est, without exposing the patient to X-Ray radiation. Based on the subjective assessment of breast stiffness by experienced medical examiners, a novel breast stiffness classification was designed, and the best method of its objective measurement was calibrated to fit the scale. Hence, this study provides an objective tool for the identification of patients who, being unable to perform valid BSE, could benefit from an increased frequency of mammography screening. Dum vivimus servimus.
IntroductionPancreatic steatosis (PS) has both metabolic consequences and local effects on the pancreas itself. Magnetic resonance imaging (MRI) is the most reliable non-invasive method for diagnosing PS. We investigated the impact of metabolic syndrome (MS) on the presence of PS, differences in individuals with and without PS, and the metabolic effects of bariatric procedures.Methods Changes in anthropometric and basic biochemistry values and MS occurrence were evaluated in 34 patients with obesity who underwent a bariatric procedure. After the procedure, patients underwent MRI with manual 3D segmentation mask creation to determine the pancreatic fat content (PFC). We compared the differences in the PFC and the presence of PS in individuals with and without MS and compared patients with and without PS.ResultsWe found no significant difference in the PFC between the groups with and without MS or in the occurrence of PS. There were significant differences in patients with and without PS, especially in body mass index (BMI), fat mass, visceral adipose tissue (VAT), select adipocytokines, and lipid spectrum with no difference in glycemia levels. Significant metabolic effects of bariatric procedures were observed.Conclusions Bariatric procedures can be considered effective in the treatment of obesity, MS, and some of its components. Measuring PFC using MRI did not show any difference in relation to MS, but patients who lost weight to BMI < 30 did not suffer from PS and had lower overall fat mass and VAT. Glycemia levels did not have an impact on the presence of PS.Graphical abstract
OBJECTIVE: The aim of the study was to evaluate the effect of body mass index on patients’ short-term results following lung lobectomy. METHODS: In this retrospective study, we compared the perioperative and short-term postoperative results of obese (BMI≥30 kg/m2) versus nonobese patients (BMI<30 kg/m2) who underwent anatomical lung resection for cancer. The two groups had the same distribution of input risk factors and the same ratio of surgical approaches (thoracoscopy vs. thoracotomy). RESULTS: The study included a total of 144 patients: 48 obese and 96 non-obese patients. Both groups had the same ratio of thoracoscopic vs. thoracotomy approach (50/50%), and were comparable in terms of demographics and clinical data. The groups did not significantly differ in the frequency of perioperative or postoperative complications. Postoperative morbidity was higher among non-obese patients (34.4 vs. 27.1%), but this difference was not statistically significant (p=0.053). Hospital stay was similar in both study groups (p=0.100). Surgery time was significantly longer among obese patients (p=0.133). Postoperative mortality was comparable between the study groups (p=0.167). CONCLUSIONS: Obesity does not increase the frequency of perioperative and postoperative complications in patients after lung lobectomy. The slightly better results in obese patients suggest that obesity may have some protective role.
Despite an increasing number of studies on caterpillar (Insecta: Lepidoptera) gut microbiota, bacteria have been emphasized more than fungi. Therefore, we lack data on whether fungal microbiota is resident or transient and shaped by factors similar to those of bacteria. We sampled nine polyphagous caterpillar species from several tree species at multiple sites to determine the factors shaping leaf and gut bacterial and fungal microbiota as well as the extent to which caterpillars acquire microbiota from their diet. We performed 16S and ITS2 DNA metabarcoding of the leaves and guts to determine the composition and richness of the respective microbiota. While spatial variables shaped the bacterial and fungal microbiota of the leaves, they only affected fungi in the guts, whereas the bacteria were shaped primarily by caterpillar species, with some species harboring more specific bacterial consortia. Leaf and gut microbiota significantly differed; in bacteria, this difference was more pronounced. The quantitative similarity between leaves and guts significantly differed among caterpillar species in bacteria but not fungi, suggesting that some species have more transient bacterial microbiota. Our results suggest the complexity of the factors shaping the gut microbiota, while highlighting interspecific differences in microbiota residency within the same insect functional group.
The diagnosis of Waldenström’s macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström’s Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.
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• Department of Informatics and Computers
• Department of Human Geography and Regional Development
• Department of Anatomy, Histology and Embryology
• Faculty of Medicine
• Department of Rehabilitation
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