Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.

• MeSH
• dítě MeSH
• elektroencefalografie * metody   MeSH
• epilepsie * terapie   patofyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• refrakterní epilepsie * terapie   patofyziologie   MeSH
• skalp MeSH
• vagová stimulace * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper summarizes the ERA Registry Annual Report 2022, with a special focus on comparisons by sex. The supplement of this paper contains the complete ERA Registry Annual Report 2022. Data was collected from 53 national and regional KRT registries from 35 countries. Using this data, incidence, and prevalence of KRT, kidney transplantation rates, survival probabilities, and expected remaining lifetimes were calculated. In 2022, 530 million people of the European general population were covered by the ERA Registry. The incidence of KRT was 152 per million population (pmp). In incident patients, 54% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes mellitus (22%). At KRT initiation, 83% of patients received haemodialysis, 12% received peritoneal dialysis, and 5% underwent pre-emptive kidney transplantation. On 31 December 2022, the prevalence of KRT was 1074 pmp. In prevalent patients, 48% were 65 years or older, 62% were male, the most common PRD was of miscellaneous origin (18%), 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. In 2022, the kidney transplantation rate was 40 pmp, with most kidneys coming from deceased donors (66%). For patients starting KRT between 2013 to 2017, 5-year survival probability was 52%. Compared with the general population, the expected remaining lifetime was 66% and 68% shorter for males and females, respectively, receiving dialysis, and 46% and 49% shorter for males and females, respectively, living with a functioning graft.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The biosynthesis of the lincosamide antibiotics lincomycin A and celesticetin involves the pyridoxal-5'-phosphate (PLP)-dependent enzymes LmbF and CcbF, which are responsible for bifurcation of the biosynthetic pathways. Despite recognizing the same S-glycosyl-L-cysteine structure of the substrates, LmbF catalyses thiol formation through β-elimination, whereas CcbF produces S-acetaldehyde through decarboxylation-coupled oxidative deamination. The structural basis for the diversification mechanism remains largely unexplored. Here we conduct structure-function analyses of LmbF and CcbF. X-ray crystal structures, docking and molecular dynamics simulations reveal that active-site aromatic residues play important roles in controlling the substrate binding mode and the reaction outcome. Furthermore, the reaction selectivity and oxygen-utilization of LmbF and CcbF were rationally engineered through structure- and calculation-based mutagenesis. Thus, the catalytic function of CcbF was switched to that of LmbF, and, remarkably, both LmbF and CcbF variants gained the oxidative-amidation activity to produce an unnatural S-acetamide derivative of lincosamide.

• MeSH
• katalytická doména MeSH
• krystalografie rentgenová MeSH
• linkosamidy * chemie   biosyntéza   metabolismus   MeSH
• pyridoxalfosfát * metabolismus   chemie   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVE: Apalutamide (APA) is a treatment for metastatic castration-sensitive prostate cancer (mCSPC). In the ARON-3 study we investigated real-world experiences with APA treatment for mCSPC. METHODS: We retrospectively assessed real-world clinical outcomes for patients with mCSPC treated with APA in the ARON-3 study. Overall survival (OS) was calculated from APA initiation to death from any cause. PSA90 was defined as a prostate-specific antigen decline of ≥90% from baseline, and PSA0.2 as achievement of a PSA level ≤0.2 ng/ml. Data for adverse events were retrospectively collected from electronic and paper charts and categorized according to Common Terminology Criteria for Adverse Events v5.0. KEY FINDINGS AND LIMITATIONS: We included 531 patients with mCSPC treated with APA. High-volume disease was reported for 214 patients (40%), and 56 (11%) had visceral metastases. Median OS was not reached. PSA90 was experienced by 461 patients (87%) and PSA0.2 by 368 (69%). Median OS was significantly longer for patients with PSA90 or PSA0.2 than for subjects without these responses (p < 0.001). The incidence of grade 3-4 fatigue was higher among elderly patients (≥80 yr) than among younger patients (19% vs 5%), but the incidence of other adverse events was comparable between the age groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: APA is an effective and tolerable treatment for mCSPC in the real-world setting. PATIENT SUMMARY: The ARON-3 project collects data for patients with prostate cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic hormone-sensitive prostate cancer receiving apalutamide. Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   patologie   mortalita   MeSH
• prostatický specifický antigen krev   MeSH
• protinádorové látky terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thiohydantoiny * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: A third of endovascularly treated patients with stroke experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3), and the natural evolution of this incomplete reperfusion remains unknown. We systematically reviewed the literature and performed a meta-analysis on the natural evolution of incomplete reperfusion after endovascular therapy. METHODS: A systematic review of MEDLINE, Embase, and PubMed up until March 1, 2024, using a predefined strategy. Only full-text English-written articles reporting rates of either favorable (ie, delayed reperfusion (DR) or no new infarct) or unfavorable progression (ie, persistent perfusion deficit or new infarct) of incompletely reperfused tissue were included. The primary outcome was the rate of DR and its association with functional independence (modified Rankin Scale score, 0-2) at 90 days postintervention. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS: Six studies involving 950 patients (50.7% female; median age, 71 years; interquartile range, 60-79) were included. Four studies assessed the evolution of incomplete reperfusion on magnetic resonance imaging perfusion imaging, while 2 studies used diffusion-weighted imaging and noncontrast computed tomography imaging, where new infarct was used to denote unfavorable progression. Five studies defined incomplete reperfusion as eTICI 2b50 or 2c. DR occurred in 41% (interquartile range, 33%-51%) of cases 24 hours postintervention. Achieving DR was associated with a higher likelihood of functional independence at 90 days (odds ratio, 2.5 [95% CI, 1.9-3.4]). CONCLUSIONS: Nearly half of eTICI <3 patients achieve DR, leading to favorable clinical outcomes. This subgroup may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (eg, intra-arterial lytics or secondary thrombectomy). Accurately predicting the evolution of incomplete reperfusion could optimize patient selection for adjunctive reperfusion strategies at the end of an intervention. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05499832.

• MeSH
• endovaskulární výkony * metody   MeSH
• ischemická cévní mozková příhoda * chirurgie   diagnostické zobrazování   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reperfuze metody   MeSH
• senioři MeSH
• trombolytická terapie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

BACKGROUND: Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population. METHODS: We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence. RESULTS: The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55-14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7-1.4) and 3.8% (3.2-4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0-34.0) of cases. A high risk of PONV was identified in 55.9% (54.3-57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1-32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6-5.2) vs 2.7% (1.9-3.8), P = .012). Factors such as specific high PONV risk surgeries ( P = .001), maintenance with inhalational agents solely ( P = .017), and neostigmine use ( P < .001) were also all statistically significant. CONCLUSIONS: Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.

• MeSH
• antiemetika terapeutické užití   MeSH
• dítě MeSH
• dodržování směrnic * normy   MeSH
• incidence MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• pooperační nevolnost a zvracení * epidemiologie   diagnóza   prevence a kontrola   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• směrnice pro lékařskou praxi jako téma normy   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
• pozorovací studie MeSH

BACKGROUND: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. OBJECTIVES: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. METHODS: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. RESULTS: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). CONCLUSIONS: This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• MeSH
• alfa-synuklein metabolismus   MeSH
• demence s Lewyho tělísky * diagnostické zobrazování   patologie   MeSH
• kognitivní dysfunkce * diagnostické zobrazování   patologie   patofyziologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• locus coeruleus * diagnostické zobrazování   patologie   MeSH
• magnetická rezonanční tomografie * MeSH
• neuropsychologické testy MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Hand and foot osteosarcoma represents ~1% of all diagnosed cases of osteosarcoma. The rarity of osteosarcoma of the hand and foot leads to frequent misdiagnosis, delayed diagnosis or incorrect treatments, which can lead to fatal consequences. Typically, salvaging the affected limb is the treatment of choice, and with the use of chemotherapy, 60-65% of patients with osteosarcoma can be treated without amputation. Due to its rarity, misdiagnosis and treatment delays are common, yet detailed reviews and analyses of such cases are limited. The present retrospective cohort study aimed to review and analyze cases of osteosarcoma located in the hand and foot. From January 2007 to January 2019, 11 patients were treated at the Masaryk Memorial Cancer Institute Sarcoma Center (Brno, Czechia), 5 cases affected the hand and 6 affected the foot. A total of 6 male patients and 5 female patients, with a mean age of 30.9±16.74 years, were diagnosed with hand or foot osteosarcoma. The mean follow-up period was 90.36±66.14 months. The mean tumor size detected during diagnosis was 4.29±1.81 cm. Osteoblastic osteosarcoma was the most common histopathological type, accounting for 4 cases (33.4%). A majority of the osteosarcomas were identified as high grade (81.8%). A total of 5 patients experienced misdiagnoses following their initial biopsy, with 2 patients initially receiving treatment outside the Masaryk Memorial Cancer Institute Sarcoma Center. The most frequently encountered misdiagnosis was giant-cell tumor of the bone. A total of 3 patients underwent limb amputation and 2 patients developed lung metastasis and succumbed to the disease. The disease-free survival period and overall survival rate were calculated using Kaplan-Meier survival analysis. The mean disease-free survival period was 82.83±60.05 months, while the overall survival rate was 72%, with a mean survival time of 90.36±56.73 months. In summary, an examination of a case series involving 11 patients diagnosed with osteosarcoma of the hand and foot was conducted. The treatment approach, clinical characteristics and patient outcomes were described. A total of four case studies of patients with osteosarcoma in the hand or foot were presented. Misdiagnosis of this disease may result in the inappropriate treatment being administered to patients, therefore, the correct and rapid diagnosis of disease is necessary for effective treatment of hand and foot osteosarcomas.

• Publikační typ
• časopisecké články MeSH

In an asymptomatic population, we investigated the relationships between glycated haemoglobin (HbA1c) and cartilage T2 relaxation time at the knee joint level. Fourteen and 17 participants with high and normal levels of HbA1c were recruited, respectively. A blood sample was used to determine the HbA1c level. T2 relaxation time (T2) of the superficial and deep parts of the femoral cartilage in the anterior, central, and posterior topographical sites was calculated using magnetic resonance (1.5 T) images. Each participant completed a knee injury and osteoarthritis outcome score questionnaire (KOOS) and a series of biomechanical analyses while running at their self-selected speed. The group with a high level of HbA1c had a lower score of KOOS symptoms than the other group (P < 0.05). HbA1c was found to be negatively related to the KOOS symptoms score. The group with a high level of HbA1c had low T2 values in all of the investigated topographical sites of the knee femoral cartilage (P < 0.05 in all cases). T2 was negatively correlated with HbA1c levels in all investigated knee femoral cartilage regions. Our data suggest that the subjects with high levels of HbA1c were those with low knee joint symptoms and lower values of T2. These results indicate that HbA1c could be correlated with cartilage deterioration due to its ability to dehydrate collagen fibre, possibly acting as a risk factor for the development of osteoarthritis.

• MeSH
• artróza kolenních kloubů krev   patofyziologie   MeSH
• dospělí MeSH
• glykovaný hemoglobin * metabolismus   MeSH
• kloubní chrupavka * metabolismus   MeSH
• kolenní kloub * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: In a previously published randomised, placebo-controlled trial, 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was shown to be superior to placebo in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). The aim of the current post hoc analyses was to evaluate the cost-effectiveness of CS compared with placebo in a European perspective using individual patient data from this clinical trial. METHODS: Patients with knee OA randomised to CS or placebo were followed up at 1, 3 and 6 months. The algo-functional Lequesne index was used to derive the EuroQol Five-Dimension Five-Level (EQ-5D-5L) score based on a validated formula. The EQ-5D-5L scores at each time point were used to calculate the changes in quality-adjusted life years (QALYs) with the area under the curve method. Costs were assessed using the average price of CS in the countries where the original study took place and where CS is currently marketed. The costs of CS in three countries were then used (i.e. the Czech Republic, Italy and Switzerland). The incremental cost-effectiveness ratio (ICER) threshold for CS to be considered cost-effective was set at 91,870 EUR per QALY (equivalent to the usually recommended threshold of US $100,000). The study used an intention-to-treat population, i.e. patients who received one dose of the study drug, and imputed missing values using the basal observation carried forward method. RESULTS: No significant differences in baseline characteristics were observed between the CS group (N = 199) and the placebo group (N = 205). The mean cost of CS for 6 months of treatment was 194.74 EUR. After 6 months of treatment, CS showed a mean ICER of 33,462 (95% CI 5130-61,794) EUR per QALY gained, indicating cost-effectiveness compared with placebo. The acceptability curve for cost-effectiveness shows that the CS treatment is likely to be cost-effective compared with placebo, with a 93% probability when the ceiling ratio is set at 91,870 EUR per QALY gained. CONCLUSIONS: These results highlight the role of CS as a cost-effective therapeutic option in the management of OA. However, further studies taking into account the use of other healthcare resources are warranted for a more complete understanding.

• MeSH
• analýza nákladové efektivity MeSH
• analýza nákladů a výnosů * MeSH
• artróza kolenních kloubů * farmakoterapie   ekonomika   MeSH
• chondroitinsulfáty * terapeutické užití   ekonomika   MeSH
• kvalitativně upravené roky života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH
• Itálie MeSH
• Švýcarsko MeSH