Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.
- MeSH
- COVID-19 * MeSH
- dospělí MeSH
- hematologické nádory * komplikace farmakoterapie epidemiologie MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- preexpoziční profylaxe * MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: There are conflicting data on the relationship between preoperative electrocardiogram and postoperative mortality. We aimed to assess the predictive value of preoperative ECG on postoperative all-cause mortality in patients undergoing non-cardiac surgery (NCS). METHODS: We retrospectively reviewed records of hospitalized patients who underwent an internal preoperative examination and subsequent NCS in the years 2015-2021. We recorded patient comorbidities, vital functions, results of biochemical tests, ECG. The primary end point was 90-day postoperative all-cause mortality, acquired from the hospital records and the nationwide registry run by the Institute of Health Information and Statistics of the Czech Republic. RESULTS: We enrolled a total of 2219 patients of mean age 63 years (48% women). Of these, 152 (6.8%) died during the 90-day postoperative period. There were statistically significant associations between increased 90-day postoperative all-cause mortality and abnormal ECG findings in resting heart rate (≥ 80 bpm, relative risk [RR] = 1.82 and ≥ 100 bpm, RR = 2.57), presence of atrial fibrillation (RR = 4.51), intraventricular conduction delay (QRS > 0.12 s, RR = 2.57), ST segment changes and T wave alterations, left bundle branch hemiblock (RR = 1.64), and right (RR = 2.04) and left bundle branch block (RR = 4.13), but not abnormal PQ and QT intervals, paced rhythm, incomplete right bundle branch block, or other ECG abnormalities. A resting heart rate (≥ 80 bpm, relative risk [RR] = 1.95 and ≥ 100 bpm, RR = 2.20), atrial fibrillation (RR = 2.10), and right bundle branch block (RR = 2.52) were significantly associated with 90-day postoperative all-cause mortality even in subgroup of patients with pre-existing cardiac comorbidities. CONCLUSIONS: Patients with abnormal preoperative ECG findings face an elevated risk of all-cause mortality within 90 days after surgery. The highest mortality risk is observed in patients with atrial fibrillation and left bundle branch block. Additionally, an elevated heart rate, right bundle branch block, and atrial fibrillation further increase the risk of death in patients with pre-existing cardiac conditions.
- MeSH
- elektrokardiografie * metody MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pooperační komplikace * mortalita epidemiologie MeSH
- prediktivní hodnota testů MeSH
- předoperační péče metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Part of the current stereotactic arrythmia radioablation (STAR) workflow is transfer of findings from the electroanatomic mapping (EAM) to computed tomography (CT). Here, we analyzed inter- and intraobserver variation in a modified EAM-CT registration using automatic registration algorithms designed to yield higher robustness. MATERIALS AND METHODS: This work is based on data of 10 patients who had previously undergone STAR. Two observers participated in this study: (1) an electrophysiologist technician (cardiology) with substatial experience in EAM-CT merge, and (2) a clinical engineer (radiotherapy) with minimum experience with EAM-CT merge. EAM-CT merge consists of 3 main steps: segmentation of left ventricle from CT (CT LV), registration of the CT LV and EAM, clinical target volume (CTV) delineation from EAM specific points. Mean Hausdorff distance (MHD), Dice Similarity Coefficient (DSC) and absolute difference in Center of Gravity (CoG) were used to assess intra/interobserver variability. RESULTS: Intraobserver variability: The mean DSC and MHD for 3 CT LVs altogether was 0.92 ± 0.01 and 1.49 ± 0.23 mm. The mean DSC and MHD for 3 CTVs altogether was 0,82 ± 0,06 and 0,71 ± 0,22 mm. Interobserver variability: Segmented CT LVs showed great similarity (mean DSC of 0,91 ± 0,01, MHD of 1,86 ± 0,47 mm). The mean DSC comparing CTVs from both observers was 0,81 ± 0,11 and MHD was 0,87 ± 0,45 mm. CONCLUSIONS: The high interobserver similarity of segmented LVs and delineated CTVs confirmed the robustness of the proposed method. Even an inexperienced user can perform a precise EAM-CT merge following workflow instructions.
- Publikační typ
- časopisecké články MeSH
Objectives: Evidence suggests that renal function increasingly deteriorates in patients with apparently treatment-resistant hypertension (ATRH) in comparison with those who have non-resistant arterial hypertension (NAH). We aimed to assess the long-term decline in renal function between these patient groups and identify specific risk factors contributing to the progression of renal dysfunction. Methods: Data for 265 patients with ATRH and NAH in a hypertension excellence centre were retrospectively evaluated. Demographic characteristics, co-morbidities, laboratory findings, secondary causes of hypertension, medication and exposure to contrast agents were assessed. To address differences between groups, adjustment with linear mixed-effect models was used. Results: Data from the first 4 years of follow-up were evaluated. After adjustment for age and diabetes, which were identified as independent risk factors for renal dysfunction progression in the study cohort, the mean decrease in estimated glomerular filtration rate per year was steeper with ATRH than with NAH (-1.49 vs. -0.65 mL/min/1.73 m2 per year; difference in slope, 0.83 mL/min/1.73 m2 per year; 95% confidence interval [CI]: 0.25-1.41, p = 0.005). In subgroup analyses, without Holm-Bonferroni correction, the prescription of MRA indicated a faster decline in renal function in ATRH. Following correction, no specific therapeutic risk factor was associated with faster progression of renal dysfunction. Conclusions: Renal function declines twice as fast with ATRH compared with NAH, independently of age and diabetes. Larger studies are needed to reveal risk factors for renal dysfunction in patients with hypertension.
- MeSH
- antihypertenziva terapeutické užití MeSH
- hodnoty glomerulární filtrace * MeSH
- hypertenze * patofyziologie farmakoterapie komplikace MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. METHODS: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). RESULTS: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). CONCLUSION: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.
- MeSH
- analýza přežití MeSH
- kohortové studie MeSH
- lidé MeSH
- malobuněčný karcinom plic * patologie MeSH
- nádory plic * radioterapie chirurgie MeSH
- nemalobuněčný karcinom plic * radioterapie chirurgie MeSH
- radiochirurgie * metody MeSH
- retrospektivní studie MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: To evaluate antibody response to mRNA vaccine, identify subgroups with poor response and to determine long-term antibody durability in hematological patients. MATERIALS AND METHODS: We have vaccinated 292 patients with all hematological malignancies with a third dose of mRNA COMIRNATY vaccine with a 12-month follow-up period in our center in Ostrava, Czech Republic. RESULTS: Antibody response for the whole cohort exceeded 74% through the whole 12-month follow-up. Lowest seroconversion was observed in CLL cohort (20/41, 48.8%), patients who received anti-CD20 therapy < 6 months before vaccination (8/30, 26.7%) and BTK inhibitors (3/6, 50.0%). On the contrary, patients with chronic myeloproliferative neoplasms and acute leukemia performed comparably with healthy population (33/33; 100% and 12/13; 92.3%, respectively). We have seen better results if the time interval between anti-CD20 therapy and additional vaccine dose was longer than 6 months (5/8 patients achieved seroconversion on 4th booster dose after previous failure). Also, 36 patients received a 4th dose of vaccine as a booster with measurable increase in protective antibodies in 50% (18/36). CONCLUSIONS: Additional doses show promise for a well-timed revaccination even in poor responders. To our knowledge, no study comparable to our work in terms of follow-up length, vaccine consistency or variety of hematological malignancies and/or treatment has been reported yet. Our findings shed more light on long-term antibody response to mRNA vaccines against SARS-CoV-2 in patients with hematological cancer and bring important data for the evaluation of possible vaccine failure and scheduling of subsequent doses.
- MeSH
- časové faktory MeSH
- COVID-19 * prevence a kontrola imunologie MeSH
- dospělí MeSH
- hematologické nádory * imunologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mRNA vakcíny MeSH
- následné studie MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vakcíny proti COVID-19 * imunologie aplikace a dávkování 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
- Geografické názvy
- Česká republika MeSH
Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.
- MeSH
- adenokarcinom * MeSH
- lidé MeSH
- mikrobiota * MeSH
- nádory plic * mikrobiologie patologie MeSH
- nemalobuněčný karcinom plic * mikrobiologie patologie MeSH
- spinocelulární karcinom * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Autosomal dominant polycystic kidney disease (ADPKD) resulting from pathogenic variants in PKD1 and PKD2 is the most common form of PKD, but other genetic causes tied to primary cilia function have been identified. Biallelic pathogenic variants in the serine/threonine kinase NEK8 cause a syndromic ciliopathy with extra-kidney manifestations. Here we identify NEK8 as a disease gene for ADPKD in 12 families. Clinical evaluation was combined with functional studies using fibroblasts and tubuloids from affected individuals. Nek8 knockout mouse kidney epithelial (IMCD3) cells transfected with wild type or variant NEK8 were further used to study ciliogenesis, ciliary trafficking, kinase function, and DNA damage responses. Twenty-one affected monoallelic individuals uniformly exhibited cystic kidney disease (mostly neonatal) without consistent extra-kidney manifestations. Recurrent de novo mutations of the NEK8 missense variant p.Arg45Trp, including mosaicism, were seen in ten families. Missense variants elsewhere within the kinase domain (p.Ile150Met and p.Lys157Gln) were also identified. Functional studies demonstrated normal localization of the NEK8 protein to the proximal cilium and no consistent cilia formation defects in patient-derived cells. NEK8-wild type protein and all variant forms of the protein expressed in Nek8 knockout IMCD3 cells were localized to cilia and supported ciliogenesis. However, Nek8 knockout IMCD3 cells expressing NEK8-p.Arg45Trp and NEK8-p.Lys157Gln showed significantly decreased polycystin-2 but normal ANKS6 localization in cilia. Moreover, p.Arg45Trp NEK8 exhibited reduced kinase activity in vitro. In patient derived tubuloids and IMCD3 cells expressing NEK8-p.Arg45Trp, DNA damage signaling was increased compared to healthy passage-matched controls. Thus, we propose a dominant-negative effect for specific heterozygous missense variants in the NEK8 kinase domain as a new cause of PKD.
- MeSH
- cilie patologie MeSH
- kationtové kanály TRPP genetika metabolismus MeSH
- kinasy NEK genetika metabolismus MeSH
- ledviny metabolismus MeSH
- lidé MeSH
- mutace MeSH
- myši MeSH
- novorozenec MeSH
- polycystická choroba ledvin * genetika MeSH
- polycystické ledviny autozomálně dominantní * patologie MeSH
- protein-serin-threoninkinasy genetika metabolismus MeSH
- serin genetika metabolismus MeSH
- transportní proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- novorozenec MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Repeated sprint ability (RSA) in soccer is deemed fundamental to ensure high level of performance. The aim of this study was to investigate the acute effects of two different Initial Heart Rates (IHR) on fatigue when testing RSA in males and females' soccer players and to compare the respective patterns of fatigue. METHODS: Nineteen female soccer players (age: 22.5±3.3 years, height 163.9±7.3 cm, body weight 54.3±6.4 kg, BMI 20.6±1.5 kg·m-2) and 15 male soccer players (age: 17.9±1.5 years, height 175.9±5.8 cm, body weight 68.5±9.6 kg, BMI 22.3±1.5 kg·m-2) participated in this study. HRs reached at the end of two different warm-up protocols (~90 vs. ~ 60% HR
- MeSH
- běh * fyziologie MeSH
- dospělí MeSH
- fotbal * fyziologie MeSH
- kyselina mléčná MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- sportovní výkon * fyziologie MeSH
- tělesná hmotnost MeSH
- únava MeSH
- zátěžový test metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
