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The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.

Článek

Effectiveness of tixagevimab/cilgavimab in patients with hematological malignancies as a pre-exposure prophylaxis to prevent severe COVID-19: a Czech retrospective multicenter study

Annals of hematology. 2024 ; 103 (3) : 981-992. [pub] 20231214

Ann Hematol
ISSN 1432-0584
Medvik
Zdroj

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

Kapitola

Vybrané kapitoly z pediatrie (2020)

Všeobecné praktické lékařství. 2024 ; () : 935-942.

ISBN 978-80-7492-713-3
Medvik
Zdroj

Článek

Screening kolorektálního karcinomu v České republice - minulost, současnost a budoucnost
[Colorectal cancer screening in the Czech Republic - past, present and future]

Gastroenterologie a hepatologie. 2024 ; 78 (5) : 378- 387.

ISSN 1804-7874
Medvik
Zdroj

Národní program screeningu kolorektálního karcinomu (KRK) probíhá v České republice od roku 2000 a je příkladem mezioborové spolupráce. Podílí se na něm specialisté z oboru gastroenterologie, praktického lékařství, gynekologie a klinické biochemie. Program je založen na dvou základních metodách – screeningovém imunochemickém testu na okultní krvácení do stolice (iTOKS, FIT) a preventivní koloskopii (TOKS-pozitivní a screeningová koloskopie). O jeho efektivitě vypovídají vysoké počty zachycených kolorektálních prekancerózních a maligních lézí. V letech 2006–2023 bylo v rámci programu provedeno 531 362 preventivních koloskopií, diagnostikováno 202 575 pacientů s adenomy (38,1 %) a 14 473 s karcinomy (2,7 %). Kvalita programu je monitorována na základě indikátorů kvality, které jsou zaměřeny na organizaci (pokrytí cílové populace) i jednotlivé metody. Pokrytí screeningovými testy ve standardním dvouletém sledování se dlouhodobě pohybuje okolo 30 %, v roce 2023 činilo 30,0 % (s výjimkou let 2020 a 2021, kdy došlo k přechodnému poklesu pokrytí na 27 % z důvodu pandemie onemocnění covidem-19). Epidemiologické ukazatele ovlivňují i nescreeningové testy, pokrytí všemi relevantními metodami ve dvouletém intervalu činilo 37,5 % v roce 2023. Koloskopie je hodnocena šesti parametry (počet vyšetření, střevní očista, totální koloskopie, záchyt adenomů celkově, u žen a u mužů). Všechny tyto indikátory splňovalo v roce 2023 celkem 72 % center pro screeningovou koloskopii. Přístroje analyzující TOKS musejí nově procházet pravidelným externím hodnocením kvality (EHK). To by mělo vést také k optimalizaci pozitivity testů, která v roce 2023 dosahovala hodnoty 9,1 %. I díky programu screeningu KRK lze pozorovat příznivé epidemiologické trendy KRK, kdy v letech 2000–2022 došlo k poklesu incidence o 32,3 % a mortality o 47,8 %. Budoucnost programu spočívá v jeho dalším zefektivňování. Cílem je navýšení pokrytí cílové populace při udržení a dalším zvyšování kvality tak, aby byl program realizovatelný a průchodný.

The National Colorectal Cancer Screening Program has been conducted in the Czech Republic since 2000 and serves as an example of interdisciplinary collaboration. Specialists from gastroenterology, general practice, gynecology, and clinical biochemistry are involved in the program. It is based on two primary methods: the screening fecal immunochemical test for occult bleeding (iFOBT, FIT) and preventive colonoscopy (FOBT-positive colonoscopy and screening colonoscopy). The program‘s effectiveness is evidenced by the high number of detected colorectal precancerous and malignant lesions. Between 2006 and 2023, a total of 531,362 preventive colonoscopies were performed, diagnosing 202,575 patients with adenomas (38.1%) and 14,473 patients with cancers (2.7%). Program quality is monitored by indicators focused on both organization (target population coverage) and screening methods. Coverage with screening tests in a 2-year interval has consistently ranged around 30%, except between 2020 and 2021 during the COVID-19 pandemic (27%), reaching 30.0% in 2023. Non-screening tests also affect epidemiological indicators, with total coverage by all relevant methods in a 2-year interval in 2023 amounting to 37.5%. Colonoscopies are evaluated using six parameters (number of examinations, bowel preparation quality, total colonoscopies, and adenoma detection rate in total, in both women and men). In 2023, 72% of screening colonoscopy centers met all of these indicators. FOBT analyzers now must have the regular external quality assessment (EQA), which should help stabilize test positivity, standing at 9.1% in 2023. Thanks to the National Colorectal Cancer Screening Program, favorable epidemiological trends have been observed, with a 32.3% decrease in incidence and a 47.8% decrease in mortality between 2000 and 2022. The future of the program lies in its further optimization, with a goal of both increasing coverage of the target population by examination and quality improvement, ensuring the program’s feasibility and efficiency.

MeSH
incidence MeSH
kolonoskopie MeSH
kolorektální nádory * diagnóza mortalita prevence a kontrola MeSH
lidé MeSH
okultní krev MeSH
plošný screening metody MeSH
primární prevence MeSH
řízení kvality MeSH
Check Tag
lidé MeSH
Publikační typ
práce podpořená grantem MeSH
přehledy MeSH
Geografické názvy
Česká republika MeSH

Článek

COVID-19 vaccination and relapse activity: A nationwide cohort study of patients with multiple sclerosis in Denmark

European journal of neurology. 2024 ; 31 (3) : e16163. [pub] 20231128

Eur J Neurol
ISSN 1468-1331
Medvik
Zdroj

BACKGROUND AND PURPOSE: We evaluated whether there was a difference in the occurrence of relapses pre- and post-COVID-19 vaccination in a nationwide cohort of Danish patients with relapsing multiple sclerosis. METHODS: We conducted a population-based, nationwide cohort study with a cutoff date of 1 October 2022. We used McNemar tests to assess changes in the proportion of patients with recorded relapses within 90 days and 180 days before and after first vaccine dose, and a negative binomial regression model to compare the 90 and 180 days postvaccination annualized relapse rate (ARR) to the 360 days prevaccination ARR. Multivariate Cox regression was used to estimate relapse risk factors. RESULTS: We identified 8169 vaccinated (87.3% Comirnaty) patients without a recorded history of a positive COVID-19 test. We did not find statistically significant changes in the proportion of patients with relapses in the 90 days (1.3% vs. 1.4% of patients, p = 0.627) and 180 days (2.7% vs. 2.6% of patients, p = 0.918) pre- and postvaccination. Also, a comparison of the ARR 360 days before (0.064, 95% confidence interval [CI] = 0.058-0.070) with the ARR 90 (0.057, 95% CI = 0.047-0.069, p = 0.285) and 180 (0.055, 95% CI = 0.048-0.063, p = 0.060) days after vaccination did not show statistically significant differences. Lower age, higher Expanded Disability Status Scale score, and relapse within 360 days before vaccination were associated with a higher risk of relapse. CONCLUSIONS: We did not find evidence of increased relapse activity following the administration of the first dose of the COVID-19 vaccine.

MeSH
chronická nemoc MeSH
COVID-19 * prevence a kontrola MeSH
kohortové studie MeSH
lidé MeSH
recidiva MeSH
relabující-remitující roztroušená skleróza * MeSH
roztroušená skleróza * MeSH
vakcinace MeSH
vakcíny proti COVID-19 terapeutické užití MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
Geografické názvy
Dánsko MeSH

Článek

Očkování u pacientů s autoimunitními revmatickými onemocněními
[Vaccination in patients with autoimmune rheumatic diseases]

Česko-slovenská dermatologie. 2024 ; 99 (4) : 155-162.

ISSN 0009-0514
Medvik
Zdroj

Pacienti se zánětlivými autoimunitními revmatickými chorobami (AIIRD) jsou vystaveni zvýšené afinitě k infekcím a jejich komplikacím. Riziko infekce stoupá se závažností orgánového postižení u AIIRD a typem a délkou imunosupresivní terapie. Celé řadě poměrně častých infekcí se dá předcházet očkováním. Očkování u nemocných s AIIRD by mělo být správně načasováno vzhledem k aktivitě choroby a terapie, aby byla dosažena jeho nejoptimálnější efektivita. Zkušenosti získané z klinických sledování, retrospektivní a prospektivní analýzy výskytu infekcí a proočkovanosti populace s AIIRD umožnily vypracovat doporučení pro očkování pod záštitou EULAR (Evropská aliance revmatologických asociací) publikované v roce 2019 a ACR (Americké revmatologické společnosti) z roku 2022. Tato doporučení zohledňují unikátní populaci pacientů s AIIRD včetně jejich terapie. Očkování může být provedeno i v průběhu léčby (kromě depleční terapie cílené na B lymfocyty), nicméně je upřednostněno ve stabilizovaném onemocnění s nižší aktivitou. Načasování očkování v rámci terapie je nutné zvážit tam, kde může být ovlivněna protilátková odpověď farmakologickými vlastnostmi podávané léčby. Očkování živými vakcínami není u imunosuprimovaných pacientů doporučováno.

Patients with inflammatory autoimmune rheumatic diseases (AIIRD) are exposed to an increased affinity for infections and their complications. The risk of infection increases with the severity of organ involvement in AIIRD and the type and duration of immunosuppressive therapy. Number of relatively common infections can be prevented by vaccination. Vaccination in patients with AIIRD should be properly timed with respect to disease activity and therapy to achieve its most optimal effectiveness. The experience gained from clinical surveillance, retrospective and prospective analyzes of the incidence of infections and vaccination coverage of the population with AIIRD allowed the development of vaccination recommendations under the auspices of EULAR (European Alliance of Rheumatology Associations) published in 2019 and ACR (American Society of Rheumatology) in 2022. These recommendations take into account the unique AIIRD patient population including their therapy. Vaccination can also be carried out during treatment (except for depletion therapy targeting B lymphocytes), however, it is preferred in stabilized disease with lower activity. The timing of vaccination within therapy must be considered where the antibody response may be influenced by the pharmacological properties of the treatment being administered. Vaccination with live vaccines is not recommended in immunosuppressed patients.