INTRODUCTION: Renal biopsy (RB) is a decisive diagnostic procedure for patients with renal disease. Our aim was to assess the safety of RB and the prevalence of associated clinical complications. METHODS: A total of 166 RBs were performed in 164 children (88 boys, 76 girls) in East Bohemia in 1997-2007. The mean age of the children was 12.9 +/- 4.1 years. All RBs were performed by a single consultant nephrologist. 27 biopsies were performed in 27 patients (16.3 percent) in 1997 under radiography control, while the remaining 139 biopsies (83.7 percent) were performed under ultrasonographic guidance. Renal ultrasonography (USG) following RB was not a general rule in patients who were biopsied under radiography control before 1998; therefore, only the USG results in patients after USG-guided RB (n = 139) were evaluated. RESULTS: No major complications were encountered, and only minor complications occurred in 39 (23.5 percent) patients, which did not require medical intervention. The most common complication was asymptomatic perirenal haematoma, which was detected by USG one to three days after a USG-guided RB (30 out of 139 biopsies; 21.6 percent). Perirenal haematoma accompanied by abdominal pain occurred in two (1.4 percent) patients. Macroscopic haematuria was present in seven (4.2 percent) patients on Days 1-3 post biopsy. The complications were neither age-dependent nor were they related to the serum creatinine levels. CONCLUSION: The results obtained are consistent with those in other reports of paediatric patients. The absence of major complications is a favourable outcome. Thus, the present practice of USG-guided percutaneous RB in children is safe and clinically beneficial.

• MeSH
• bezpečnost MeSH
• biopsie škodlivé účinky   metody   MeSH
• dítě MeSH
• hematom diagnóza   MeSH
• hematurie diagnóza   MeSH
• jehlová biopsie škodlivé účinky   metody   MeSH
• kojenec MeSH
• ledviny patologie   MeSH
• lidé MeSH
• mladiství MeSH
• nemoci ledvin diagnóza   patologie   MeSH
• pediatrie metody   MeSH
• předškolní dítě MeSH
• reprodukovatelnost výsledků MeSH
• ultrasonografie metody   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. METHODS: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. RESULTS: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. CONCLUSIONS: No safety concerns arose, supporting the favorable benefit-risk profile of RZV.

• Klíčová slova
• Reactogenicity, Safety, Vaccine, Varicella-zoster virus,
• MeSH
• adjuvancia imunologická aplikace a dávkování   škodlivé účinky   MeSH
• herpes zoster prevence a kontrola   MeSH
• interpretace statistických dat MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• syntetické vakcíny aplikace a dávkování   škodlivé účinky   MeSH
• vakcína proti pásovému oparu aplikace a dávkování   škodlivé účinky   genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• syntetické vakcíny MeSH
• vakcína proti pásovému oparu MeSH

Food packaging waste significantly impacts global environmental changes, prompting the adoption of a green circular economy approach. Recycling packaging waste is a critical element of this strategy. However, it faces challenges related to the quality of recycled materials and concerns about their safety. Thus, this review aimed to highlight different analytical methods alone or in combination to evaluate the quality of the recycled material. Furthermore, the safety and health aspects related to the migration of contaminants and their relevant regulations have also been discussed. An important parameter while selecting an appropriate recycling method is the composition and nature of the recyclate, for instance, HDPE (High-Density Polyethylene), PET (Polyethylene Terephthalate), and PP (Polypropylene) materials can be recycled using mechanical and chemical recycling, however, PVC (Polyvinyl Chloride) and PS (Polystyrene) present challenges during mechanical recycling due to lower molecular weight and complex compositions, thus are often downcycled into lower-grade products. Still, recycled papers can be more problematic than recycled plastics due to the nature of the materials and the impact of recycling. The literature review suggested that three quality properties i.e., presence of low molecular weight compounds, degree of degradation, and composition should be analyzed by using different spectroscopic, thermo-mechanical, and chromatographic techniques to obtain a detailed understanding of recycled material quality. Furthermore, recycling should be done in such a way that the migration of contaminants should be lower than the migratory limits set by the relevant authorities to avoid any toxicological effects.

• Klíčová slova
• Green economy, Migration analysis, Quality assessment techniques, Recycled packaging waste, Safety concerns,
• MeSH
• nakládání s odpady metody   MeSH
• obaly potravin * MeSH
• plastické hmoty MeSH
• recyklace * metody   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• plastické hmoty MeSH

BACKGROUND: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). METHODS AND RESULTS: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5-20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site-interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8-24), and washout (weeks 24-28), and included major adverse cardiac events, new-onset atrial fibrillation, implantable cardioverter-defibrillator discharges, LVEF <50%, and treatment-emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5-, 10-, 15-, and 20-mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by -0.9% (95% CI, -1.3 to -0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per-protocol dose reduction for site-interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment-emergent adverse events were similar between treatment groups, including atrial fibrillation. CONCLUSIONS: A site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05186818.

• Klíčová slova
• aficamten, cardiac myosin inhibitor, hypertrophic cardiomyopathy,
• MeSH
• benzylaminy MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fibrilace síní farmakoterapie   diagnóza   patofyziologie   MeSH
• funkce levé komory srdeční * účinky léků   MeSH
• hypertrofická kardiomyopatie * patofyziologie   farmakoterapie   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• tepový objem * účinky léků   MeSH
• uracil analogy a deriváty   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• benzylaminy MeSH
• MYK-461 MeSH Prohlížeč
• uracil MeSH

Balloon pulmonary angioplasty (BPA) is a novel treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not eligible for pulmonary endarterectomy (PEA) or suffer from persistent pulmonary hypertension after PEA. The aim of this study was to evaluate the real-life efficacy and safety of BPA in a consecutive group of patients who were diagnosed and treated in the national referral center for CTEPH in the Czech Republic. Here we report data from 160 BPA procedures performed in 64 patients. Efficacy analysis was performed in the subgroup of 25 patients who completed BPA series. Significant improvements were observed in New York Heart Association functional class (4% to 79% in I/II, p < 0.001), 6 min walking test distance (+54.3 m, p < 0.001), risk profile (15.8% to 68.5% with presence of 2/3 low risk criteria, p < 0.001), pulmonary artery mean pressure (-18%, p < 0.001), pulmonary vascular resistance (-32%, p < 0.001), stroke volume (+17%, p = 0.011) and quality of life (+37% in assessment of overall health status by a patient, p < 0.001). We observed 1 fatal periprocedural complication (1.6% of all 64 patients) and 19 BPA-related non-fatal complications (11.9% of all 160 interventions) that predominantly included hemoptysis (10.0% of all sessions). Overall survival at 12 months was 94.6%.

• Klíčová slova
• balloon pulmonary angioplasty, chronic thromboembolic pulmonary hypertension, efficacy, quality of life, risk profile, safety, survival,
• Publikační typ
• časopisecké články MeSH

Carfilzomib is a selective proteasome inhibitor approved for the treatment of relapsed and/or refractory multiple myeloma (RRMM). It has significantly improved outcomes, including overall survival (OS), and shown superiority vs standard treatment with lenalidomide plus dexamethasone and bortezomib plus dexamethasone. The incidence rate of cardiovascular (CV) events with carfilzomib treatment has varied across trials. This analysis evaluated phase 1-3 trials with >2000 RRMM patients exposed to carfilzomib to describe the incidence of CV adverse events (AEs). In addition, the individual CV safety data of >1000 patients enrolled in the carfilzomib arm of phase 3 studies were compared with the control arms to assess the benefit-risk profile of carfilzomib. Pooling data across carfilzomib trials, the CV AEs (grade ≥3) noted included hypertension (5.9%), dyspnea (4.5%), and cardiac failure (4.4%). Although patients receiving carfilzomib had a numeric increase in the rates of any-grade and grade ≥3 cardiac failure, dyspnea, and hypertension, the frequency of discontinuation or death due to these cardiac events was low and comparable between the carfilzomib and control arms. Serial echocardiography in a blinded cardiac substudy showed no objective evidence of cardiac dysfunction in the carfilzomib and control arms. Moreover, carfilzomib had no significant effect on cardiac repolarization. Our results, including the OS benefit, showed that the benefit of carfilzomib treatment in terms of reducing progression or death outweighed the risk for developing cardiac failure or hypertension in most patients. Appropriate carfilzomib administration and risk factor management are recommended for elderly patients and patients with underlying risk factors.

• MeSH
• incidence MeSH
• kardiovaskulární nemoci chemicky indukované   epidemiologie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   epidemiologie   MeSH
• oligopeptidy škodlivé účinky   terapeutické užití   MeSH
• recidiva MeSH
• rizikové faktory MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• carfilzomib MeSH Prohlížeč
• oligopeptidy MeSH

In recent years increasing pressure to limit the powers of the Czech public health authorities in the field of food safety has been noticed. An approach to safe food production and official controls depends on diverse and complex socioeconomic factors in the context of political and legislative framework within which food producers and official controllers exist. Official controls are those activities carried out by the competent authorities (CA) or delegated bodies) in Member States to verify business compliance with the requirements set out in agri-food chain legislation. The presented text compares the effectiveness of national food safety systems in the Member States (MS) of the European Union (EU). Under the current EU legislation, each MS shall appoint the competent authorities responsible for the purposes of European legislation in the field of food safety and for performance of official controls. Member States shall ensure that official controls are carried out regularly, on a risk basis and with appropriate frequency to achieve the objectives set out in the European legislation. For evaluation were used the country profiles of Member States, as published in 2011-2015. From the perspective of the European Commission current system of official controls in the Czech Republic is rated as one of the most effective and least problematic. When comparing various systems in Member States it is not possible to decide which control system is more efficient, i.e. system based on one competent authority or relying on several competent authorities.

• Klíčová slova
• European Union, effectiveness, food safety, member states, system of official controls,
• MeSH
• bezpečnost potravin metody   MeSH
• Evropská unie MeSH
• lidé MeSH
• veřejné zdravotnictví zákonodárství a právo   MeSH
• zákonodárství potravinářské * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

UNLABELLED: The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3-4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = .817) or hemorrhagic events (p = 1.000). Grade 3-4 non-hematologic TEAEs were rare (the incidence of grade 3-4 pneumonia, e.g. was 5.6% in the lenalidomide group and 2.5% in the placebo group). Common grade 1-2 non-hematologic TEAEs did not require dose modifications or treatment discontinuation. Acute myeloid leukemia and second primary malignancies incidence was similar across treatment groups. Lenalidomide had a predictable and manageable safety profile in lower-risk non-del(5q) MDS patients ineligible/refractory to ESAs. Guidance on managing lenalidomide-related TEAEs is provided to help maintain patients on therapy to achieve maximum clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01029262.

• Klíčová slova
• Myeloid leukemias and dysplasias, immunotherapy, manipulation of the immune response,
• MeSH
• chromozomální delece MeSH
• dospělí MeSH
• exantém chemicky indukované   MeSH
• imunologické faktory škodlivé účinky   terapeutické užití   MeSH
• lenalidomid škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 5 MeSH
• myelodysplastické syndromy farmakoterapie   genetika   MeSH
• neutropenie chemicky indukované   MeSH
• průjem chemicky indukované   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spasmus chemicky indukované   MeSH
• únava chemicky indukované   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• imunologické faktory MeSH
• lenalidomid MeSH

The European Food Safety Authority (EFSA) has been involved in the risk assessment of novel foods since 2003. The implementation of the current novel food regulation in 2018 rendered EFSA the sole entity of the European Union responsible for such safety evaluations. The risk assessment is based on the data submitted by applicants in line with the scientific requirements described in the respective EFSA guidance document. The present work aims to elaborate on the rationale behind the scientific questions raised during the risk assessment of novel foods, with a focus on complex mixtures and whole foods. Novel foods received by EFSA in 2003-2019 were screened and clustered by nature and complexity. The requests for additional or supplementary information raised by EFSA during all risk assessments were analyzed for identifying reoccurring issues. In brief, it is shown that applications concern mainly novel foods derived from plants, microorganisms, fungi, algae, and animals. A plethora of requests relates to the production process, the compositional characterization of the novel food, and the evaluation of the product's toxicological profile. Recurring issues related to specific novel food categories were noted. The heterogeneous nature and the variable complexity of novel foods emphasize the challenge to tailor aspects of the evaluation approach to the characteristics of each individual product. Importantly, the scientific requirements for novel food applications set by EFSA are interrelated, and only a rigorous and cross-cutting approach adopted by the applicants when preparing the respective application dossiers can lead to scientifically sound dossiers. This is the first time that an in-depth analysis of the experience gained by EFSA in the risk assessment of novel foods and of the reasoning behind the most frequent scientific requests by EFSA to applicants is made.

• Klíčová slova
• EFSA, Food safety, Mixtures, Novel foods, Nutrition, Risk assessment, Safety assessment, Whole foods,
• MeSH
• bezpečnost potravin * MeSH
• Evropská unie MeSH
• hodnocení rizik MeSH
• potraviny * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Roundabouts are one of the safest types of intersections. However, the needs to meet the requirements of operation, capacity, traffic organization and surrounding development lead to a variety of design solutions. One of such alternatives are turbo-roundabouts, which simplify drivers' decision making, limit lane changing in the roundabout, and induce low driving speed thanks to raised lane dividers. However, in spite of their generally positive reception, the safety impact of turbo-roundabouts has not been sufficiently studied. Given the low number of existing turbo-roundabouts and the statistical rarity of accident occurrence, the prevalent previously conducted studies applied only simple before-after designs or relied on traffic conflicts in micro-simulations. Nevertheless, the presence of raised lane dividers is acknowledged as an important feature of well performing and safe turbo-roundabouts. Following the previous Polish studies, the primary objective of the present study was assessment of influence of presence of lane dividers on road safety and developing a reliable and valid surrogate safety measure based on field data, which will circumvent the limitations of accident data or micro-simulations. The secondary objective was using the developed surrogate safety measure to assess and compare the safety levels of Polish turbo-roundabout samples with and without raised lane dividers. The surrogate safety measure was based on speed and lane behaviour. Speed was obtained from video observations and floating car data, which enabled the construction of representative speed profiles. Lane behaviour data was gathered from video observations. The collection of the data allowed for a relative validation of the method by comparing the safety performance of turbo-roundabouts with and without raised lane dividers. In the end, the surrogate measure was applied for evaluation of safety levels and enhancement of the existing safety performance functions, which combine traffic volumes, and speeds as a function of radii). The final models may help quantify the safety impact of different turbo-roundabout solutions.

• Klíčová slova
• Floating car data, Lane divider, Speed, Surrogate safety measure, Turbo-Roundabout, Video observation,
• MeSH
• audiovizuální záznam MeSH
• bezpečnost MeSH
• dopravní nehody prevence a kontrola   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• řízení motorových vozidel statistika a číselné údaje   MeSH
• sběr dat metody   MeSH
• vytvořené prostředí * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH