BACKGROUND: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application. OBJECTIVE: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs). METHODS: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios. sNfL levels were defined as "high" (>90th percentile) vs "normal" (<80th percentile), based on normative values of control persons. In three rounds, 10 international and 18 Swiss MS experts, and 3 patient consultants rated their agreement on treatment algorithms. Consensus thresholds were defined as moderate (50%-79%), broad (80%-94%), strong (≥95%), and full (100%). RESULTS: The Delphi provided 9 escalation algorithms (e.g. initiating treatment based on high sNfL), 11 horizontal switch (e.g. switching natalizumab to another high-efficacy DMT based on high sNfL), and 3 de-escalation (e.g. stopping DMT or extending intervals in B-cell depleting therapies). CONCLUSION: The consensus reached on typical clinical scenarios provides the basis for using sNfL to inform treatment decisions in a randomized pragmatic trial, an important step to gather robust evidence for using sNfL to inform personalized treatment decisions in clinical practice.

• Klíčová slova
• Delphi study, de-escalation, escalation, personalized treatment strategies, serum neurofilament light chain,
• MeSH
• algoritmy * MeSH
• delfská metoda MeSH
• dospělí MeSH
• imunologické faktory * terapeutické užití   MeSH
• individualizovaná medicína * metody   MeSH
• klinické rozhodování * metody   MeSH
• konsensus MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurofilamentové proteiny * krev   MeSH
• roztroušená skleróza * krev   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunologické faktory * MeSH
• neurofilament protein L MeSH Prohlížeč
• neurofilamentové proteiny * MeSH

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

• Klíčová slova
• Botulinum toxin, Consensus guidelines, Dose limits, Dose variability, Dosing tables, Dystonia, Spasticity, Target muscles, Therapy, Total dose, Treatment algorithms, Typical dose,
• MeSH
• algoritmy MeSH
• botulotoxiny typu A * MeSH
• botulotoxiny * MeSH
• dystonické poruchy * farmakoterapie   MeSH
• dystonie * farmakoterapie   MeSH
• lidé MeSH
• svalová spasticita farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• botulotoxiny typu A * MeSH
• botulotoxiny * MeSH

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment.

• MeSH
• akutní lymfatická leukemie terapie   MeSH
• delfská metoda MeSH
• dítě MeSH
• kombinovaná terapie škodlivé účinky   MeSH
• konsensus MeSH
• lidé MeSH
• nežádoucí účinky léčiv etiologie   prevence a kontrola   MeSH
• testy akutní toxicity MeSH
• tolerance záření * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In the early twenty-first century, societies around the world are facing the paradoxal epidemic development of PCa as a non-communicable disease. PCa is the most frequently diagnosed cancer for men in several countries such as the USA. Permanently improving diagnostics and treatments in the PCa management causes an impressive divergence between, on one hand, permanently increasing numbers of diagnosed PCa cases and, on the other hand, stable or even slightly decreasing mortality rates. Still, aspects listed below are waiting for innovate solutions in the context of predictive approaches, targeted prevention and personalisation of medical care (PPPM / 3PM).A.PCa belongs to the cancer types with the highest incidence worldwide. Corresponding economic burden is enormous. Moreover, the costs of treating PCa are currently increasing more quickly than those of any other cancer. Implementing individualised patient profiles and adapted treatment algorithms would make currently too heterogeneous landscape of PCa treatment costs more transparent providing clear "road map" for the cost saving.B.PCa is a systemic multi-factorial disease. Consequently, predictive diagnostics by liquid biopsy analysis is instrumental for the disease prediction, targeted prevention and curative treatments at early stages.C.The incidence of metastasising PCa is rapidly increasing particularly in younger populations. Exemplified by trends observed in the USA, prognosis is that the annual burden will increase by over 40% in 2025. To this end, one of the evident deficits is the reactive character of medical services currently provided to populations. Innovative screening programmes might be useful to identify persons in suboptimal health conditions before the clinical onset of metastasising PCa. Strong predisposition to systemic hypoxic conditions and ischemic lesions (e.g. characteristic for individuals with Flammer syndrome phenotype) and low-grade inflammation might be indicative for specific phenotyping and genotyping in metastasising PCa screening and disease management. Predictive liquid biopsy tests for CTC enumeration and their molecular characterisation are considered to be useful for secondary prevention of metastatic disease in PCa patients.D.Particular rapidly increasing PCa incidence rates are characteristic for adolescents and young adults aged 15-40 years. Patients with early onset prostate cancer pose unique challenges; multi-factorial risks for these trends are proposed. Consequently, multi-level diagnostics including phenotyping and multi-omics are considered to be the most appropriate tool for the risk assessment, prediction and prognosis. Accumulating evidence suggests that early onset prostate cancer is a distinct phenotype from both aetiological and clinical perspectives deserving particular attention from view point of 3P medical approaches.

• Klíčová slova
• 3PM), Adapted treatment algorithms, Adolescence, Aetiology, Age, Aggressive metastatic disease, Alcohol consumption, Androgen dependent, Apoptosis resistance, Biomarker patterns, Body mass index BMI, Bone-specific alkaline phosphatase, C-index, Castration resistant, Choline, Circulating tumour cells (CTC), Coffee, Comorbidities, Curcumin, Diet, Disease manifestation, Economy, Elderly, Ellargic acid, Ethics, Ethnicity, Family history, Fish, Folate, Fruits, Garlic, Genetic, Green tea, Gut microbiota, Human development index, Hybrid imaging, Incidence, Indicator, Individualised patient profile, Inflammation, Insulin-like growth factor, Ischemic lesions, Lactate dehydrogenase, Life quality, Lifestyle, Liquid biopsy, Lycopene, Malignancy, Meat, Microcirculation, Modifiable risk factors, Mortality, Multi-factorial systemic disease, Multi-omics, Multi-parametric analysis, Obesity, Oxidative stress, PET/MRI, PSA screening, Patient stratification, Personalised nutrition, Physical activity, Prebiotics, Predictive preventive personalised medicine (PPPM, Probiotics, Prognosis, Prostate cancer (PCa), Prostate cancer antigen 3, Quercetin, Race, Radical prostatectomy, Risk assessment, Roadmap, Saturated fat, Selenium/selenite, Sexually transmitted diseases, Sleep disorders, Smoking, Socio-economic factors, Stillbenes, Sulphorapane, Survival, Systemic hypoxic condition, Toxic environment, Trace elements, Transrectal ultrasound, Trends, Urinary tract infection, Urology, Vasectomy, Vegetables, Vitamins A, C, D, E, and K, Young population, miRNA,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. METHODS: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I - III) stage Ib-IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with the same chemotherapy for 2 to 3 months prior to surgery. PET-non-responders switched to preoperative chemoradiotherapy [weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions)]. Here, we aim to confirm the feasibility of FDG-PET-based response assessment in a multicenter setting and to compare local versus central reading. In addition, we report on the feasibility of the study conduct and patient safety data. RESULTS: A total of 64 patients received baseline and sequential 14-day 18FDG-PET/CT scanning. And, 63 were allocated to the respective treatment arm according to PET-response [35 (56%) responders and 28 (44%) non-responders]. The concordance of local versus central reading of SUV changes was 100%. Until the date of this analysis, 47 patients (28 responders and 19 non-responders) completed surgery. Postoperative complications of grade ⩾ 3 (Common Terminology Criteria for Adverse Events, CTCAE Version 5.0) were reported in five responders (18%; 95% CI: 7.9-36%) and two non-responders (11%; 95% CI: 2.9-31%), with no statistical difference (p = 0.685). One patient in each arm died after surgery, leading to a postoperative in-hospital mortality rate of 4.3% (2/47 patients; 95% CI: 1.2-14%). CONCLUSION: Local and central FDG-SUV quantification and PET-response assessment showed high concordance. This confirms the accuracy of a PET-response-guided treatment algorithm for locally advanced oesophago-gastric junction cancer in a multicenter setting. Preoperative treatment adaptation revealed feasible and safe for patients.

• Klíčová slova
• PET/CT-guided preoperative treatment strategy, localised oesophago-gastric junction adenocarcinoma, metabolic imaging, non-responders,
• Publikační typ
• časopisecké články MeSH

At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.

• Klíčová slova
• biomarkers, burden of disease, cognitive dysfunction, magnetic resonance imaging, multiple sclerosis, neurofilament,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Multiple myeloma (MM) is a malignancy with varying survival outcomes and drivers of disease progression. Existing MM staging tools were developed using data from newly diagnosed patients. As patient characteristics and disease-related factors change between diagnosis and the initiation of second-line (2L) treatment, an unmet need exists for a tool that can evaluate risk of death at first relapse. We have developed a risk stratification algorithm (RSA) using data from patients with MM who were at 2L. Hazard ratios for independent predictors of overall survival (OS) were derived from a Cox models, and individual patient scores were calculated for total risk. K-adaptive partitioning for survival was used to stratify patients into groups based on their scores. Relative risk doubled with ascending risk group; median OSs for patients in group 1 (lowest risk)-4 (highest risk) were 61·6, 29·6, 14·2 and 5·9 months, respectively. Differences in OS between risk groups were significant. Similar stratification was observed when the RSA was applied to an external validation data set. In conclusion, we have developed a validated RSA that can quantify total risk, frailty risk and disease aggressiveness risk, and stratify patients with MM at 2L into groups with profoundly different survival expectations.

• Klíčová slova
• algorithm, multiple myeloma, overall survival, relapsed, risk stratification,
• MeSH
• algoritmy * MeSH
• analýza přežití MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   mortalita   patologie   MeSH
• recidiva MeSH
• registrace MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

INTRODUCTION: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report provides guidance on effective management of chronic obstructive pulmonary disease (COPD) according to local healthcare systems. However, COPD is a heterogenous disease and certain aspects, including prevalence, disease-time course and phenotype distribution, can differ between countries. Moreover, features of clinical practice and healthcare systems for patients with COPD can vary widely, even in geographically close and economically similar countries. AREAS COVERED: Based on an initial workshop of respiratory physicians from eleven countries across Central and Eastern Europe (CEE) in December 2018 and subsequent discussions, this article offers region-specific insights from clinical practice and healthcare systems in CEE. Taking recommendations from the GOLD 2022 report into account, we suggest approaches to adapt these into national clinical guidelines for COPD management in CEE. EXPERT OPINION: Several factors should be considered when optimizing management of COPD in CEE compared with other regions, including differences in smoking status, vaccination uptake, prevalence of tuberculosis and nontuberculous mycobacteria, and variations in healthcare systems. We provide guidance and algorithms for pharmacologic and non-pharmacologic management of COPD for the following scenarios: initial and follow-up treatment, treatment of patients with frequent exacerbations, and withdrawal of inhaled corticosteroids where appropriate.

Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs. It causes symptoms such as breathlessness, cough, and production of phlegm. In people with COPD, these symptoms often reduce the quality of their lives. From time to time, symptoms may get worse in people with the disease. This worsening is known as ‘exacerbation’. Exacerbations of COPD can be so bad that they lead to hospital admissions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) regularly gives advice to doctors around the world. This can help them to provide their patients with the best possible treatment for COPD. However, people with the disease and healthcare systems vary from country to country. This means that the guidance may need to be adjusted to the needs and available resources of different regions. This review looks at how COPD is treated in Central and Eastern Europe. We suggest how to adapt the GOLD recommendations to best suit the Central and Eastern European region.

• Klíčová slova
• Central and Eastern Europe, Chronic obstructive pulmonary disease, algorithms, clinical guidelines, exacerbations, inhaled corticosteroids, non-pharmacologic management, pharmacologic management,
• MeSH
• chronická obstrukční plicní nemoc * diagnóza   epidemiologie   terapie   MeSH
• fenotyp MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• lidé MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• hormony kůry nadledvin MeSH

Defining reproducible criteria for lower extremity salvage following severe high-energy trauma continues to be one of the most challenging and controversially discussed fields in orthopaedic surgery. At present, however, the difficult performance, limited availability and number of valid reconstructive options for complex injury types, i. e. simultaneous osteoligamentous trauma with neurovascular lesions and severe soft tissue defects ("composite/compound multilayer defects") represent the decisive prognostic injury components triggering and determining the fate of the limb. Consequently, due to the complex injury pattern of the extremity and the overall situation of multiple injured patient the treatment and decision making has to be made in a priority-adapted algorithm. In this treatment algorithm interdisciplinary cooperation with vascular and plastic surgeons is of tremendous importance. Although the number of severely injured patients remains stable in the last decade, changes in the treatment algorithms result from increased survival rates of multiple injured patients and improved modern reconstructive options leading to continuously increasing rates of salvaged limbs. This paper aimed to systematically review the current literature for lower extremity injuries in order to unravel the different surgical treatment options and provide guidelines for decision making with corresponding treatment algorithms for limb salvage. Furthermore, the experiences in the management of mangled extremities in our centre are presented and illustrated/underscored with different cases.

• MeSH
• algoritmy MeSH
• lidé MeSH
• polytrauma * etiologie   patofyziologie   chirurgie   MeSH
• poranění cév chirurgie   MeSH
• poranění dolní končetiny * etiologie   patofyziologie   chirurgie   MeSH
• poranění měkkých tkání chirurgie   MeSH
• poranění periferního nervu chirurgie   MeSH
• replantace * škodlivé účinky   metody   MeSH
• skóre závažnosti úrazu MeSH
• záchrana končetiny * škodlivé účinky   metody   MeSH
• zákroky plastické chirurgie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Aromatic ring-peptide bond interactions (modeled as benzene and formamide, N-methylformamide and N-methylacetamide) are studied by means of advanced computational chemistry methods: second-order Möller-Plesset (MP2), coupled-cluster single and double excitation model [CCSD(T)], and density functional theory with dispersion (DFT-D). The geometrical preferences of these interactions as well as their interaction energy content, in both parallel and T-shaped arrangements, are investigated. The stabilization energy reaches a value of over 5 kcal/mol for the N-methylformamide-benzene complex at the CCSD(T)/complete basis set (CBS) level. Decomposition of interaction energy by the DFT-symmetry-adapted perturbation treatment (SAPT) technique shows that the parallel and T-shaped arrangements, although similar in their total interaction energies, differ significantly in the proportion of electrostatic and dispersion terms.

• MeSH
• algoritmy MeSH
• benzen chemie   MeSH
• chemické modely MeSH
• molekulární modely MeSH
• peptidy chemie   MeSH
• přenos energie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzen MeSH
• peptidy MeSH