Direct mailing of HPV self-sampling kits to women aged 50-65 non-participating in cervical screening in the Czech Republic.

BACKGROUND: A population-based cervical cancer screening programme is implemented in the Czech Republic. However, participation is insufficient among women over 50 years. This study aimed to estimate the potential improvement in participation through directly mailed HPV self-sampling kits (HPVssk) compared with standard invitation letters in women aged 50-65 non-participating in screening. METHODS: The study recruited 1564 eligible women (no cervical cancer screening in the last 3 years or more, no previous treatment associated with cervical lesions or cervical cancer). Eight hundred women were mailed with an HPVssk (HPVssk group), and 764 women were sent a standard invitation letter (control group) inviting them to a routine screening (Pap test). The primary outcome was a comparison of the overall participation rate between study groups using a binominal regression model. RESULTS: The participation rate in the HPVssk group was 13.4% [95% confidence interval (CI) 11.2-15.9%; 7.4% of women returned the HPVssk and 6.0% attended gynaecological examination] and 5.0% (95% CI 3.6-6.8%) in the control group. Using the binominal regression model, the difference between the groups was estimated as 7.6% (95% CI 5.0-10.2%; P < 0.001). In the HPVssk group, 22% of women who returned HPVssk had a positive result and 70% of them underwent a follow-up examination. CONCLUSIONS: Compared with traditional invitation letters, the direct mailing of the HPVssk achieved a significantly higher participation rate, along with a notable HPV positivity rate among HPVssk responders. This approach offers a potentially viable method for engaging women who have not yet attended a cervical screening programme.

Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study.

BACKGROUND: Glutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population. METHODS: We analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr). RESULTS: The GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively). CONCLUSIONS: This study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

Trends in the representation of specialties caring for patients with diabetes in the Czech Republic.

The increasing prevalence of diabetes mellitus (DM) leads to the differentiation of the registration of diabetics in individual specialties. Objective of this paper was the evaluation of changes in the representation of expertise providing care for patients with DM (pDM) in the Czech Republic, based on data analysis from the National Register of Paid Health Services (NRHZS) 2010-2021. In the entire pDM group, the number of patients treated by a diabetologist (DIA) increased from 491,490 (57.0 %) to 537,430 (50.4 %), with a general practitioner (GP) from 27,719 (3.2 %) to 181,330 (17.0 %) and by internist (INT) from 172,918 (20.0 %) to 161,291 (15.1 %). In 2021, 57.9 % DIA, 17 % GP, 12.2 % INT were treated from the group treated with antidiabetics (813,873). In 2021, 84,345 were treated with insulin alone (87.2 % DIA), 129,127 were treated with a combination of insulin and non-insulin antidiabetics; 115,604 (91.6 %) in DIA, 322 (0.3 %) in GP and 7,983 (6.3 %) in INT. 603,331 treated only with non-insulin antidiabetic drugs, of which 281,929 (46.7 %) DIA, 137,744 (22.8 %) GP and 85,273 (14.1 %) INT. For other specialties, 98,385 (16.3 %) persons. 185,838 patients without reported DIA/GP/INT control, of which 80,144 without therapy. The increasing prevalence of DM and changes in reimbursement conditions are reflected in the dynamic development of the distribution of diabetes care by individual specialties.

Gene polymorphisms and serum levels of mannose-binding lectin in Czech patients with recurrent aphthous stomatitis: A case-control study.

BACKGROUND: Recurrent aphthous stomatitis is one of the most prevalent oral mucosal immunological diseases. A recent case-control study in the Egyptian population suggested that single nucleotide polymorphism Gly54Asp (rs1800450) of the mannose-binding lectin 2 gene might affect the mannose-binding lectin serum level and recurrent aphthous stomatitis development. The aim of this study was to determine the distribution of six functional mannose-binding lectin 2 gene polymorphisms and analyse their role in recurrent aphthous stomatitis susceptibility in the Czech population. METHODS: The study included 227 subjects; 137 healthy people and 90 patients with recurrent aphthous stomatitis. Six mannose-binding lectin 2 gene polymorphisms (rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451) were analysed by the SNaPshot assay method, mannose-binding lectin serum levels were determined by enzyme-linked immunosorbent assay (ELISA) method in a subgroup of subjects (N = 87). RESULTS: No significant differences in mean of mannose-binding lectin serum levels between healthy controls and patients with recurrent aphthous stomatitis were observed (383 ng/ml ± 249 standard deviation (SD) vs. 316 ng/ml ± 177 SD in remission phase vs. 343 ng/ml ± 254 SD in active phase; p > 0.05), also the allele and genotype frequencies of the studied mannose-binding lectin 2 polymorphisms did not differ significantly between the two groups (p > 0.05, odds ratio (OR): 0.75-1.23). Moreover, the distribution of mannose-binding lectin 2 haplotypes and haplogenotypes was similar in the healthy subjects and patients with recurrent aphthous stomatitis (p > 0.05, OR: 0.75-1.23). CONCLUSIONS: This study did not confirm the previously reported association of the mannose-binding lectin 2 Gly54Asp gene variant and low mannose-binding lectin serum level as the risk factors for susceptibility to recurrent aphthous stomatitis. In addition, no significant relationships between mannose-binding lectin 2 functional haplotypes or haplogenotypes and recurrent aphthous stomatitis were observed.

Coverage by examinations associated with early detection of colorectal neoplasia in the Czech Republic.

BACKGROUND: Coverage by examinations is a crucial indicator of the future impact on the burden of colorectal cancer (CRC). The study aimed to evaluate coverage by examinations associated with CRC screening and early cancer detection of CRC in the Czech Republic. The burden of CRC was also assessed. METHODS: The novel nationwide administrative registry with individual data (period 2010-19) was used to evaluate coverage by examinations for screening faecal occult blood test and colonoscopy. In the second step, additional examinations for early CRC detection were included in the coverage calculation (complete coverage). Age-specific trends in CRC incidence (period 1977-2018) were investigated using Joinpoint regression. RESULTS: Coverage by screening examinations within recommended interval was around 30%. Complete coverage reached >37% and >50% at the 3-year interval. The coverage by examinations for the non-screening population aged 40-49 years was almost 4% and 5% (most of them were colonoscopies) at the 3-year interval. In age groups aged ≥50 years, we observed a significant annual decline, especially in the 50-69 age group, with recent annual decreases reaching up to 5-7%. The change in trend and the recent decline were also observed in the age group 40-49. CONCLUSIONS: More than half of the target screening population was covered by examinations potentially associated with early detection and subsequent treatment of colorectal neoplasms. The substantial coverage by potentially prophylactic examinations might be an explanation for the considerable decrease in CRC incidence.

Association Between SARS-CoV-2 Messenger RNA Vaccines and Lower Infection Rates in Kidney Transplant Recipients : A Registry-Based Report.

BACKGROUND: The real-world protection provided by SARS-CoV-2 messenger RNA (mRNA) vaccines to kidney transplant recipients (KTRs) remains uncertain. OBJECTIVE: To study the association between mRNA vaccination and SARS-CoV-2 infection rate in KTRs. DESIGN: Retrospective observational cohort study. SETTING: The Czech Republic (17 February to 16 May 2021). PATIENTS: 2101 KTRs followed in the Department of Nephrology at the Institute for Clinical and Experimental Medicine. MEASUREMENTS: Positive result for SARS-CoV-2 on polymerase chain reaction test and vaccination status of KTRs. RESULTS: The incidence rate in the vaccinated group was 0.474 per 1000 person-days (33 cases in 69 672 days at risk). The incidence rate in the unvaccinated group was 1.370 per 1000 person-days (79 cases in 57 658 days at risk). The unadjusted incidence rate ratio (IRR; incidence rate of vaccinated/incidence rate of unvaccinated) for KTRs was 0.346 (95% CI, 0.227 to 0.514). The multivariable adjusted IRR for KTRs was 0.544 (CI, 0.324 to 0.876). LIMITATION: Retrospective observational design, uneven follow-up of patient groups, and different exposition to SARS-CoV-2 stemming from strong temporal trends and differences in clinical and probably behavioral characteristics. CONCLUSION: Vaccination of KTRs is associated with lower risk for SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: The Ministry of Health of the Czech Republic.

CD14 Polymorphism Is Not Associated with SARS-CoV-2 Infection in Central European Population.

A 2021 in silico study highlighted an association between the CD14 polymorphism rs2569190 and increased susceptibility to SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19). The aim of our study was to confirm this finding. We analysed the CD14 polymorphism (C→T; rs2569190) in 516 individuals who tested positive for SARS-CoV-2, with differing disease severity (164 asymptomatic, 245 symptomatic, and 107 hospitalized). We then compared these patients with a sample from the general population consisting of 3,037 individuals using a case-control study design. In comparison with carriers of the C allele, TT homozygotes accounted for 21.7 % of controls and 20.5 % in SARS-CoV-2-positive individuals (P = 0.48; OR; 95 % CI - 0.92; 0.73-1.16). No significant differences in the distribution of genotypes were found when considering co-dominant and recessive genetic models or various between-group comparisons. The CD14 polymorphism is unlikely to be an important predictor of COVID-19 in the Caucasian population in Central Europe.

Possible effect of OAS1 and TMPRSS6 but not DPP4 and ZNF335 polymorphisms on COVID-19 severity in the Czech population.

OBJECTIVES: The acute respiratory syndrome, known as COVID-19, is characterised by high morbidity and increased mortality. Genetic factors may partially explain the differences in susceptibility to and severity of COVID-19. METHODS: We have analysed common functional polymorphisms within the OAS1 (rs4767027), TMPRSS6 (rs855791), DPP4 (rs3788979), and ZNF335 (rs3848719) genes in SARS-CoV-2 positive subjects (n = 521, different disease severity) and in population controls (n = 2,559 subjects, COVID-19 status unknown). RESULTS: Neither DPP4 nor ZNF335 were associated with disease susceptibility or severity in the Czech population in any of the models used for calculation. T allele carriers of the OAS1 polymorphism seem to be protective against symptomatic COVID-19 (p = 0.002 calculated for trend; asymptomatic, symptomatic, hospitalised). Similarly, within the TMPRSS6, minor TT homozygotes associated with lower plasma Fe concentrations were underrepresented in the overall patient group (p = 0.044; OR = 0.77, 95% CI: 0.59-0.99), and the difference was mainly driven by the severe COVID-19 subjects. In general, risky homozygotes of these two polymorphisms were less frequent than expected in the group of hospitalised COVID-19 survivors. CONCLUSIONS: Common variants within OAS1 (rs4767027) and TMPRSS6 (rs855791) play some role in COVID-19 pathology in the Czech Caucasian population. Whether the depletion of minor allele carriers of these two variants is associated with increased COVID-19 mortality, needs to be analysed in an external confirmatory study.

Registration of a pregnant woman in the maternity hospital (optimally at 36th-37th weeks) at the Olomouc University Hospital in 2022.

OBJECTIVE: The aim of the study was to analyse the results of the implementation of the new health service Registration of a pregnant woman in the maternity hospital (optimally at 36th-37th weeks) provided as part of outpatient/ambulatory health care at Olomouc University Hospital (OUH). MATERIALS AND METHODS: A prospective cohort study. In 2022, a total of 2,271 women gave birth in OUH, and 2,010 of them were Registered in the maternity hospital, defined specific risks were identified and a pregnancy termination strategy was established/determined. RESULTS: The health service was provided to 88.5% of women giving birth (2,010/2,271). The age of the mothers was 15-56 years (mean 31.3 years; median 31 years), their body mass index was 13.4-53.1 kg/m2 (mean 24.6 kg/m2; median 23.2 kg/m2). 43.6% of them (877/2,010) were Low-risk pregnancies and 56.4% (1,133/2,010) were Pregnancies with a defined specific risk. The most frequently identified risks were as follows: RhD negative blood group (18.4%), diabetes mellitus (13.9%), history of caesarean section (12.0%), hypertensive disorders (6.5%), small fetus/fetal growth restriction (6.3%), risk the development of hemolytic disease in the fetus and the newborn (2.5%), multiple pregnancy (1.6%), congenital malformation of the fetus (1.3%) and placentation disorders (0.5%). In 63.4% of them (1,275/2,010), the pregnancy termination strategy was determined by spontaneous vaginal delivery, in 18.0% (361/2,010) by pre-induction of vaginal delivery and in 14.2% (285/2,010) by caesarean section. In 4.4% (89/2,010) the health service was not implemented correctly because no strategy was established. CONCLUSION: The implementation of the new health service will make it possible to replace activity (more frequent antenatal care contacts/visits and routine antenatal cardiotocography) with efficiency (risk identification, determination of the optimal strategy for outpatient/ambulatory antenatal care and timing and mode of delivery) and thereby provide better and safer health care (from a medical, organizational, legislative and economic points of view).

Morphological types of sella turcica bridging and sella turcica dimensions in relation to palatal canine impaction: a retrospective study.

The aim of this study was to determine the relationship between the presence of sella turcica bridging and palatal canine impaction (PCI) using several classification methods. In this retrospective study, lateral cephalometric radiographs of 120 subjects with PCI (43 males, 77 females; mean age 18.8 ± 7.8 years) and 120 controls (44 males, 76 females; mean age 18.1 ± 5.6 years) with complete permanent dentition were examined. The extent of sella turcica bridging was assessed using two different methods, and the types of complete sella turcica bridging were evaluated. The sella turcica dimensions were measured and analyzed using the t-test, and comparison of the presence of sella turcica bridging was performed using the two-tailed Fisher's exact test. The frequency of complete sella turcica bridging was significantly higher in subjects with PCI (18.3%) than in controls (8.3%, p = 0.023) but without significant differences in the occurrence of sella turcica bridging of Type A (ribbon-like fusion) and Type B (extension of clinoid processes). No significant differences in partial bridging were found between patients with PCI and controls according to both methods. The length and the anteroposterior diameter were significantly larger in subjects with PCI and no difference was observed between the groups in the sella turcica depth. Complete sella turcica bridging occurred significantly more frequently in subjects with PCI than in controls. However, the association between partial bridging and PCI was not confirmed, therefore, we do not recommend any classification of partial bridging for clinical practice.

Control Centre for Intensive Care as a Tool for Effective Coordination, Real-Time Monitoring, and Strategic Planning During the COVID-19 Pandemic.

In the Czech Republic, the strategic data-based and organizational support for individual regions and for providers of acute care at the nationwide level is coordinated by the Ministry of Health. At the beginning of the COVID-19 pandemic, the country needed to very quickly implement a system for the monitoring, reporting, and overall management of hospital capacities. The aim of this viewpoint is to describe the purpose and basic functions of a web-based application named "Control Centre for Intensive Care," which was developed and made available to meet the needs of systematic online technical support for the management of intensive inpatient care across the Czech Republic during the first wave of the pandemic in spring 2020. Two tools of key importance are described in the context of national methodology: one module for regular online updates and overall monitoring of currently free capacities of intensive care in real time, and a second module for online entering and overall record-keeping of requirements on medications for COVID-19 patients. A total of 134 intensive care providers and 927 users from hospitals across all 14 regions of the Czech Republic were registered in the central Control Centre for Intensive Care database as of March 31, 2021. This web-based application enabled continuous monitoring and decision-making during the mass surge of critical care from autumn 2020 to spring 2021. The Control Center for Intensive Care has become an indispensable part of a set of online tools that are employed on a regular basis for crisis management at the time of the COVID-19 pandemic.

Association of the angiotensin I converting enzyme (ACE) gene polymorphisms with recurrent aphthous stomatitis in the Czech population: case-control study.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is multifactorial disease with unclear etiopathogenesis. The aim of this study was to determine distribution of the angiotensin I converting enzyme (ACE) gene polymorphisms and their influence on RAS susceptibility in Czech population. METHODS: The study included 230 subjects (143 healthy controls and 87 patients with RAS) with anamnestic, clinical and laboratory data. Five ACE gene polymorphisms (rs4291/rs4305/rs4311/rs4331/rs1799752 = ACE I/D) were determined by TaqMan technique. RESULTS: The allele and genotype distributions of the studied ACE I/D polymorphisms were not significantly different between subjects with/without RAS (Pcorr > 0.05). However, carriers of II genotype were less frequent in the RAS group (OR = 0.48, 95% CI = 0.21-1.12, P = 0.059). Stratified analysis by sex demonstrated lower frequency of II genotype in women (OR = 0.33, 95% CI = 0.09-1.17, P < 0.035, Pcorr > 0.05, respectively) than in men with RAS (P > 0.05). Moreover, the frequency of AGTGD haplotype was significantly increased in RAS patients (OR = 13.74, 95% CI = 1.70-110.79, P = 0.0012, Pcorr < 0.05). In subanalysis, TGD haplotype was significantly more frequent in RAS patients (P < 0.00001) and CGI haplotype was less frequent in RAS patients (P < 0.01), especially in women (P = 0.016, Pcorr > 0.05). CONCLUSIONS: Our study indicates that while the AGTGD and TGD haplotypes are associated with increased risk of RAS development, CGI haplotype might be one of protective factors against RAS susceptibility in Czech population.

Screening for congenital defects and genetic diseases of the fetus at University Hospital in Olomouc and sending/ reporting to the National register of reproductive health in the Czech Republic.

OBJECTIVE: The aim of the study was to analyze the results of the screening for congenital defects (CD) and genetic diseases (GD) of the fetus in the Fetal Medicine Centre at the Department of Obstetrics and Gynecology, University Hospital in Olomouc. MATERIALS AND METHODS: Prospective cohort study. In the period from 1 January 2020 to 31 December 2021, a total of 14,460 health services were performed on 4,916 pregnant women. Within the screening of CD and GD of the fetus, 501 pregnant women were found to have an abnormality requiring further clinical management, 170 of them were diagnosed with a CD of the fetus and in 20 cases a GD of the fetus was diagnosed by a laboratory genetic examination. All diagnosed fetal CD and GD were sent/ reported according to the valid methodology of the National health information system (NHIS) to the National register of reproductive health (NRRH) to the CD Module. RESULTS: An increased calculated individual risk of genetic fetal disease was diagnosed in the first trimester of pregnancy in 10.7% of fetuses (319/ 2,968), and in the second trimester in 0.9% of fetuses (27/ 2,948). Nuchal translucency (NT) > 3.5 mm was diagnosed in 0.9% of fetuses by ultrasound examination in the first trimester of pregnancy (26/ 2,968). In fetal CD and GD screening, 501 pregnant women were found to have an abnormality requiring further clinical management, 72.1% of women (361/ 501) had an increased risk of genetic fetal disease, and diagnostic examination of the fetal genetic material obtained by invasive procedure (chorionic villus sampling or amniocentesis) was indicated. A total of 31.3% of them (113/ 361) refused the invasive procedure and 2.5% (9/ 361) did not attend the planned procedure; the invasive procedure was performed in 66.2% (239/ 361). CONCLUSION: Comparing the results of CD and GD fetal screening in our medical facility with other specialized medical facilities in the Czech Republic is currently difficult to do, but information from the NRRH could allow objective and transparent comparisons in the future.

Voiding recovery after radical parametrectomy in cervical cancer patients: An international prospective multicentre trial - SENTIX.

OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in <7 days and 293 (97.7%) in <30 days. Only seven (2.3%) patients recovered after >30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.

SETAP: epidemiology and prevention of stroke and transient ischaemic attack in Czech patients with atrial fibrillation.

AIMS: The aim of this study is to analyse the prevalence, epidemiology, and anticoagulation prevention of stroke or transient ischaemic attack (TIA) in Czech patients with atrial fibrillation (AF). METHODS AND RESULTS: Retrospective observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Healthcare Services between 2015 and 2018. Prevalence of AF in 2018 was 4.3% of Czech population and the prevalence of stroke/TIA in AF patients was 22.3% with annual incidence of 181.62 cases per 100 000 inhabitants. In 2018, CHA2DS2-ASc score ≥4 was present in 98% AF patients in secondary and 59% in primary prevention, respectively, while the anticoagulation treatment was used by 71-81% of them. Between 2015 and 2018, the percentage of AF patients treated with warfarin monotherapy in primary prevention decreased from 35% to 31%, with acetylsalicylic acid (ASA) monotherapy from 18% to 16% and non-vitamin K antagonist oral anticoagulants (NOACs) monotherapy increased from 7% to 11%. In secondary prevention, the percentage of warfarin monotherapy treatment decreased from 35% to 32%, with ASA monotherapy from 20% to 18% and with NOACs monotherapy increased from 9% to 15%. CONCLUSION: This study followed all Czech patients with AF. The unadjusted prevalence and incidence of AF was higher compared with other countries and 2019 European Society of Cardiology Statistics. The study identified several gaps in standard of reimbursed care. 20-30% of AF patients with other risk factors were without any prevention medication and the share of ASA monotherapy in treated patients was 16-18%.

The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis.

BACKGROUND: Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. METHODS: The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. RESULTS: The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9). CONCLUSIONS: EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.

Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis.

BACKGROUND: The development of recurrent aphthous stomatitis (RAS), inflammatory disease of oral mucosa, is influenced by both environmental and genetic factors. The aim of this study was to investigate polymorphisms located in seven genes coding different types of matrix metalloproteinases (MMPs)-collagenases (MMP1, MMP8, and MMP13), gelatinases (MMP2 and MMP9), stromelysin (MMP3), and membrane-type metalloproteinase (MMP16) in patients with RAS and healthy controls. METHODS: Totally, 223 subjects were included in this case-control study and their detailed anamnestic, clinical, and laboratory parameters were recorded. Seventy-seven patients with RAS and 146 controls were genotyped for seventeen polymorphisms in the MMPs genes using the real-time polymerase chain reaction (PCR) or PCR with restriction analysis. RESULTS: Allele, genotype, and haplotype frequencies of the studied polymorphisms between RAS patients and controls were similar, except for allele distributions of MMP1 rs1144393, MMP9 rs3918242, and MMP16 rs10429371, which were different between patients with RAS and healthy controls (P = .023, P = .049 and P = .025, all Pcorr  > 0.05, respectively). Moreover, the comparison of genotype frequencies (TT vs CC + CT) of the MMP16 rs10429371 variant showed a marginally significant difference between RAS patients and controls (P = .05, Pcorr  > 0.05, OR = 1.68, 95% CI = 0.95-2.98). CONCLUSIONS: No significant relationship between investigated polymorphisms in seven MMPs genes and RAS development in the Czech population was observed in this study.

Oncologic outcome after completing or abandoning (radical) hysterectomy in patients with cervical cancer and intraoperative detection of lymph node positivity; ABRAX (ABandoning RAd hyst in cerviX cancer).

BACKGROUND: The management of patients with intraoperative detection of lymph node involvement remains controversial. The most significant aspect is the decision regarding the completion of the cervical procedure, such as hysterectomy, radical hysterectomy, or a fertility sparing procedure. PRIMARY OBJECTIVE: The primary objective of the ABandoning RAd hyst in cerviX cancer (ABRAX) trial is to determine whether the completion of the cervical procedure (ie, radical hysterectomy) improves oncological outcome in patients with intraoperatively detected lymph node involvement before they are referred for definitive chemoradiation. STUDY HYPOTHESIS: We hypothesize that, in patients with intraoperative lymph node involvement, completion of radical hysterectomy or other cervical procedure does not improve the oncological outcome of definitive chemoradiation. TRIAL DESIGN: The ABRAX trial is a multicenter, retrospective, cohort study. Patients with negative lymph nodes in clinical staging, in whom lymph node involvement is detected intraoperatively, are included. Completion or abandonment of the planned cervical procedure stratifies the cohort into two subgroups in which oncological outcome and morbidity will be compared. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with early stage (pT1a-pT2b) cervical cancer, who did not have positive lymph nodes on preoperative imaging, who were scheduled for primary surgical treatment, and in whom metastatic involvement of pelvic lymph node was found during surgery either as a grossly (macroscopically) involved or on intraoperative pathology assessment will be enrolled. Patients can be included irrespective of surgical approach (minimal invasive surgery or laparotomy) and type of cervical procedure performed (hysterectomy, radical hysterectomy, or a fertility sparing procedure). PRIMARY ENDPOINT: The primary endpoint of this retrospective study is a progression free survival in two subgroups with abandoned or completed cervical procedure followed by definitive chemoradiation in both groups. SAMPLE SIZE: The assumed sample size is 718 patients (in total for both groups). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated end of data collection: December 2019; estimated date of presenting results: Q2/3 2020. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04037124.

Impact of sentinel lymph node frozen section evaluation to avoid combined treatment in early-stage cervical cancer.

BACKGROUND: The need for radical surgery followed by adjuvant chemoradiation may be reduced by abandoning radical surgery in patients in whom lymph node involvement is detected intra-operatively. OBJECTIVES: To analyze, in a retrospective cohort study, the efficacy of the algorithm using intra-operative pathological assessment of sentinel lymph nodes. METHODS: A retrospective single-institution study was carried out, which analyzed data from all consecutive patients with cervical cancer who were referred for primary surgical treatment between May 2005 and December 2015. Inclusion criteria were as follows: (1) TNM stage T1a1 with lymphovascular space invasion, T1a2, T1b, T2a, and selected T2b with incipient parametrial invasion; (2) adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma; (3) no evidence of enlarged suspicious nodes or distant metastases on pre-operative imaging; (4) primary surgery with curative intent; (5) successful detection of sentinel lymph node, at least, unilaterally. All patients had at least one sentinel lymph node detected and submitted for frozen section evaluation. When sentinel lymph node involvement was detected intra-operatively, the cervical procedure was abandoned and the patient was referred for definitive chemoradiation. Radical surgery was completed in patients with intra-operative negative sentinel lymph nodes. The reliability of intra-operative sentinel lymph node assessment was evaluated by calculating the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: The study included a total of 309 patients. Sentinel lymph nodes were detected bilaterally in 86% of the patients. Lymph node positivity was detected intra-operatively in 18 (6%) patients in whom the cervical procedure was abandoned. Adjuvant radiotherapy after completed radical surgery was given to 29 (9%) patients, including 20 patients with macrometastases (8) or micrometastases (12) reported from the final histology, eight patients with positive parametria (all ≤3 mm), and one patient with a positive vaginal resection margin. The sensitivity, specificity, positive predictive value, and negative predictive value for the intra-operative detection of lymph node positivity (macrometastases or micrometastases) was 47% (95% CI 31% to 64%), 100%, 100%, and 93% (95% CI 90% to 96%), respectively. A total of 18 (6%) patients were spared combined treatment owing to the intra-operative sentinel lymph node triage; 29 patients (9%) received combined treatment with both radical surgery and adjuvant radiotherapy CONCLUSIONS: Of 47 patients with high-risk prognostic risk factors (lymph node, parametria, or surgical margin involvement), combined treatment was successfully avoided in 18 (38%). Despite an effort to triage the patients intra-operatively, 9% received a combination of cervical procedure and adjuvant chemoradiation, mostly owing to the low sensitivity of the frozen section in the detection of micrometastases and macrometastases.

Complex Reporting of the COVID-19 Epidemic in the Czech Republic: Use of an Interactive Web-Based App in Practice.

BACKGROUND: The beginning of the coronavirus disease (COVID-19) epidemic dates back to December 31, 2019, when the first cases were reported in the People's Republic of China. In the Czech Republic, the first three cases of infection with the novel coronavirus were confirmed on March 1, 2020. The joint effort of state authorities and researchers gave rise to a unique team, which combines methodical knowledge of real-world processes with the know-how needed for effective processing, analysis, and online visualization of data. OBJECTIVE: Due to an urgent need for a tool that presents important reports based on valid data sources, a team of government experts and researchers focused on the design and development of a web app intended to provide a regularly updated overview of COVID-19 epidemiology in the Czech Republic to the general population. METHODS: The cross-industry standard process for data mining model was chosen for the complex solution of analytical processing and visualization of data that provides validated information on the COVID-19 epidemic across the Czech Republic. Great emphasis was put on the understanding and a correct implementation of all six steps (business understanding, data understanding, data preparation, modelling, evaluation, and deployment) needed in the process, including the infrastructure of a nationwide information system; the methodological setting of communication channels between all involved stakeholders; and data collection, processing, analysis, validation, and visualization. RESULTS: The web-based overview of the current spread of COVID-19 in the Czech Republic has been developed as an online platform providing a set of outputs in the form of tables, graphs, and maps intended for the general public. On March 12, 2020, the first version of the web portal, containing fourteen overviews divided into five topical sections, was released. The web portal's primary objective is to publish a well-arranged visualization and clear explanation of basic information consisting of the overall numbers of performed tests, confirmed cases of COVID-19, COVID-19-related deaths, the daily and cumulative overviews of people with a positive COVID-19 case, performed tests, location and country of infection of people with a positive COVID-19 case, hospitalizations of patients with COVID-19, and distribution of personal protective equipment. CONCLUSIONS: The online interactive overview of the current spread of COVID-19 in the Czech Republic was launched on March 11, 2020, and has immediately become the primary communication channel employed by the health care sector to present the current situation regarding the COVID-19 epidemic. This complex reporting of the COVID-19 epidemic in the Czech Republic also shows an effective way to interconnect knowledge held by various specialists, such as regional and national methodology experts (who report positive cases of the disease on a daily basis), with knowledge held by developers of central registries, analysts, developers of web apps, and leaders in the health care sector.