- MeSH
- lidé MeSH
- nealkoholová steatóza jater * epidemiologie MeSH
- rizikové faktory MeSH
- zdraví žen MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.
BACKGROUND: ATP-binding cassette (ABC) transporters translocate various substances across cellular membranes. Their deregulation may cause cancer drug resistance or perturbations in the supply of building blocks for cancer cells and modify patients' prognosis. This study investigated protein expression and cellular localization of the previously suggested putative prognostic biomarkers - ABCB2/TAP1, ABCC7/CFTR, ABCC8/SUR1, and ABCD4 in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Protein expression and localization were assessed by immunohistochemistry in formalin-fixed paraffin-embedded primary tumor tissue blocks of 61 PDAC patients and associated with clinical data and the survival of patients. RESULTS: No CFTR protein expression was observed in PDAC, while TAP1 and ABCC8 were expressed predominantly in the cytoplasm of tumor cells. Most samples (81 %) had detectable both membranous and cytoplasmic ABCD4 staining and 42 % had ABCD4 expressed in the apical orientation. Negative membranous ABCD4 staining was significantly more frequent in advanced stage III or IV tumors (p = 0.022). Small or medium counts of individual ABCC8-positive cells in the stroma surrounding tumor tubules were also more often found in stage III or IV (p = 0.044). Patients with moderate or strong ABCC8 cytoplasmic staining intensity in tumor cells had a 3.5-fold higher risk of disease progression than those with weak staining (p = 0.002). CONCLUSIONS: The study shows for the first time that the cytoplasmic ABCC8 protein expression has prognostic value in PDAC.
- MeSH
- ABC transportéry genetika MeSH
- adenokarcinom * patologie MeSH
- duktální karcinom pankreatu * patologie MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory slinivky břišní * diagnóza patologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- receptory sulfonylurey * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Kidney transplant recipients are at risk for a severe course of COVID-19 with a high mortality rate. A considerable number of patients remains without a satisfactory serological response after the baseline and adjuvant SARS-CoV-2 vaccination schedule. METHODS: In this prospective, randomized study, we evaluated the efficacy and safety of one and two booster doses of mRNA vaccines (either mRNA-1273 or BNT162b2) in 125 COVID-19 naive, adult kidney transplant recipients who showed an insufficient humoral response (SARS-CoV-2 IgG <10 AU/ml) to the previous 2-dose vaccination schedule. The primary outcome was the difference in the rate of a positive antibody response (SARS-CoV-2 IgG ≥10 AU/ml) between one and two booster doses at 1 month after the final booster dose. RESULTS: A positive humoral response was observed in 36 (62%) patients receiving two booster doses and in 28 (44%) patients receiving one booster dose (odds ratio [OR], 2.10, 95% confidence interval [CI], 1.02-4.34, p = .043). Moreover, median SARS-CoV-2 IgG levels were higher with two booster doses (p = .009). The number of patients with positive virus neutralizing antibody (VNA) levels was numerically higher with two booster doses compared to one booster dose, but without statistical significance (66% vs. 50%, p = .084). There was no significant difference in positive seroconversions rate and antibody levels between mRNA-1273 and BNT162b2. CONCLUSION: A higher number of kidney transplant recipients achieved a positive antibody response after two booster doses compared to one booster dose.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- dospělí MeSH
- imunoglobulin G MeSH
- lidé MeSH
- mRNA vakcíny MeSH
- příjemce transplantátu MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 MeSH
- vakcína firmy Moderna proti COVID-19 MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.
- MeSH
- duktální karcinom pankreatu * MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nádory slinivky břišní * etiologie genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Mechanistic data indicate the benefit of short-chain fatty acids (SCFA) produced by gut microbial fermentation of fiber on colorectal cancer, but direct epidemiologic evidence is limited. A recent study identified SNPs for two SCFA traits (fecal propionate and butyrate-producing microbiome pathway PWY-5022) in Europeans and showed metabolic benefits. METHODS: We conducted a two-sample Mendelian randomization analysis of the genetic instruments for the two SCFA traits (three SNPs for fecal propionate and nine for PWY-5022) in relation to colorectal cancer risk in three large European genetic consortia of 58,131 colorectal cancer cases and 67,347 controls. We estimated the risk of overall colorectal cancer and conducted subgroup analyses by sex, age, and anatomic subsites of colorectal cancer. RESULTS: We did not observe strong evidence for an association of the genetic predictors for fecal propionate levels and the abundance of PWY-5022 with the risk of overall colorectal cancer, colorectal cancer by sex, or early-onset colorectal cancer (diagnosed at <50 years), with no evidence of heterogeneity or pleiotropy. When assessed by tumor subsites, we found weak evidence for an association between PWY-5022 and risk of rectal cancer (OR per 1-SD, 0.95; 95% confidence intervals, 0.91-0.99; P = 0.03) but it did not surpass multiple testing of subgroup analysis. CONCLUSIONS: Genetic instruments for fecal propionate levels and the abundance of PWY-5022 were not associated with colorectal cancer risk. IMPACT: Fecal propionate and PWY-5022 may not have a substantial influence on colorectal cancer risk. Future research is warranted to comprehensively investigate the effects of SCFA-producing bacteria and SCFAs on colorectal cancer risk.
- MeSH
- butyráty * analýza metabolismus MeSH
- feces * chemie mikrobiologie MeSH
- kolorektální nádory * epidemiologie genetika metabolismus MeSH
- kyseliny mastné těkavé analýza genetika metabolismus MeSH
- lidé MeSH
- mendelovská randomizace MeSH
- propionáty * analýza metabolismus MeSH
- riziko MeSH
- střevní mikroflóra * genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Evropa MeSH
SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .
- MeSH
- antivirové látky škodlivé účinky MeSH
- cytomegalovirové infekce * epidemiologie MeSH
- Cytomegalovirus genetika MeSH
- lidé MeSH
- neutropenie * chemicky indukované komplikace MeSH
- příjemce transplantátu MeSH
- transplantace ledvin * škodlivé účinky MeSH
- valganciklovir škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.
- MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- incidence MeSH
- lidé MeSH
- messenger RNA MeSH
- mRNA vakcíny MeSH
- pandemie MeSH
- příjemce transplantátu MeSH
- prospektivní studie MeSH
- protilátky virové MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- syntetické vakcíny MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: Compared to unattended office blood pressure (uOBP), attended office blood pressure (aOBP) is higher. It is not known, however, to what extent distance between physician and patient influences blood pressure (BP) values. MATERIALS AND METHODS: Participants were stable hypertensive patients, followed in the university hospital-based out-patient center. During a session, automated office BP was measured three times after a pre-set five-minute pause, using the Omron 907 device; both aOBP and uOBP were done, in a random order. Simultaneously, beat-to-beat BP measurement was performed using the Finapress device. During aOBP, some participants were in close contact with the physician while others were in loose contact where the doctor was sitting in the room about 2.5 m apart. One year later, the second session with the same protocol was organized, but the close and loose contact were interchanged. The data were analyzed using a paired t-test. RESULTS: Complete data were collected in 32 patients, baseline uOBP was 122.8 ± 14.8/69.5 ± 11.7 mmHg. Systolic and diastolic aOBP with close contact was higher by 4.6 ± 6.9 and 1.9 ± 3.4 mmHg (p < 0.0007 and 0.0039, respectively), while aOBP with loose contact was not different from uOBP. Beat-to-beat BP increased during aOBP by 6.5 ± 8.5/3.3 ± 4.8 mmHg. The increase persisted during all the three aOBP measurements (p < 0.0001 for all systolic and diastolic BP values); the results were similar for close and loose contact. The peak increase during uOBP was of similar magnitude as during aOBP but it lasted shorter: it reached the significance level of p < 0.0001 only during the first uOBP measurement. CONCLUSIONS: Compared to uOBP, aOBP values were higher with close, but not with loose contact between physician and patient. These differences were, however, not detected by beat-to-beat BP measurement.
- MeSH
- ambulantní monitorování krevního tlaku metody MeSH
- automatizace MeSH
- hypertenze * diagnóza MeSH
- krevní tlak MeSH
- lékaři * MeSH
- lidé MeSH
- měření krevního tlaku metody MeSH
- systolické šelesty * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60-75] years of age; males: 67%; body mass index: 30.1 [27.0-34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national-international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.
- MeSH
- COVID-19 * epidemiologie terapie MeSH
- dospělí MeSH
- jednotky intenzivní péče MeSH
- kyslík MeSH
- lidé MeSH
- registrace MeSH
- respirační insuficience * epidemiologie terapie MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- sepse * epidemiologie MeSH
- syndrom dechové tísně * MeSH
- umělé dýchání MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
