Rapid triage and transfer system for patients with proven Covid-19 at emergency department.

BACKGROUND: COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis. METHODS: The triage algorithm assessed self-sufficiency, oximetry, systolic blood pressure, and the Glasgow coma scale. Compliance with the triage protocol was defined as fulfillment of all protocol steps, including assignment of the correct level of care. Triage was considered successful if there was no change in the scope of care (e.g., unscheduled hospital admission, transfer to different level of care) or if there was unexpected death within 48 hours. RESULTS: A total of 929 patients were enrolled in the study. Triage criteria were fulfilled in 825 (88.8%) patients. Within 48 hours, unscheduled hospital admission, transfer to different level of care, or unexpected death occurred in 56 (6.0%), 6 (0.6%), and 5 (0.5%) patients, respectively. The risk of unscheduled hospital admission or transfer to different level of care was significantly increased if triage criteria were not fulfilled [13.1% vs. 76.1%, RR 5.8 (3.8-8.3), p < 0.001; 0.5% vs. 5.2%, RR 11.4 (2.3-57.7), p = 0.036, respectively]. CONCLUSION: The proposed algorithm for triage of patients with proven COVID-19 is a simple, fast, and reliable tool for rapid sorting for outpatient treatment, hospitalization on a standard ward, or assignment to an intensive care unit.

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders.

BACKGROUND: Neurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality of intellectual and social abilities and common daily functioning. The rapid development of exome sequencing (ES) techniques, together with trio-based analysis, nowadays leads to up to 50% diagnostic yield. Therefore, it is considered as the state-of-the-art approach in these diagnoses. RESULTS: In our study, we present the results of ES in a cohort of 85 families with 90 children with severe NDDs and MCAs. The interconnection of the in-house bioinformatic pipeline and a unique algorithm for variant prioritization resulted in a diagnostic yield of up to 48.9% (44/90), including rare and novel causative variants (41/90) and intragenic copy-number variations (CNVs) (3/90). Of the total number of 47 causative variants, 53.2% (25/47) were novel, highlighting the clinical benefit of ES for unexplained NDDs. Moreover, trio-based ES was verified as a reliable tool for the detection of rare CNVs, ranging from intragenic exon deletions (GRIN2A, ZC4H2 genes) to a 6-Mb duplication. The functional analysis using PANTHER Gene Ontology confirmed the involvement of genes with causative variants in a wide spectrum of developmental processes and molecular pathways, which form essential structural and functional components of the central nervous system. CONCLUSION: Taken together, we present one of the first ES studies of this scale from the central European region. Based on the high diagnostic yield for paediatric NDDs in this study, 48.9%, we confirm trio-based ES as an effective and reliable first-tier diagnostic test in the genetic evaluation of children with NDDs.

Vaccination against tick-borne encephalitis elicits a detectable NS1 IgG antibody response.

Vaccine-induced protection against tick-borne encephalitis virus (TBEV) is mediated by antibodies to the viral particle/envelope protein. The detection of non-structural protein 1 (NS1) specific antibodies has been suggested as a marker indicative of natural infections. However, recent work has shown that TBEV vaccines contain traces of NS1, and immunization of mice induced low amounts of NS1-specific antibodies. In this study, we investigated if vaccination induces TBEV NS1-specific antibodies in humans. Healthy army members (n = 898) were asked to fill in a questionnaire relating to flavivirus vaccination or infection, and blood samples were collected. In addition, samples of 71 suspected acute TBE cases were included. All samples were screened for the presence of TBEV NS1-specific IgG antibodies using an in-house developed ELISA. Antibodies were quantified as percent positivity in reference to a positive control. For qualitative evaluation, cut-off for positivity was defined based on the mean OD of the lower 95% of the vaccinated individuals + 3 SD. We found significantly higher NS1-specific IgG antibody titers (i.e., quantitative evaluation) in individuals having received 2, 3, or 4 or more vaccine doses than in non-vaccinated individuals. Similarly, the percentage of individuals with a positive test result (i.e., qualitative evaluation) was higher in individuals vaccinated against tick-borne encephalitis than in unvaccinated study participants. Although NS1-specific IgG titers remained at a relatively low level when compared to TBE patients, a clear distinction was not always possible. Establishing a clear cut-off point in detection systems is critical for NS1-specific antibodies to serve as a marker for distinguishing the immune response after vaccination and infection.

A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio­based exome sequencing: A case report.

Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer­predisposing Bloom syndrome. The present study reports on a case of an infant with a congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using a routine molecular diagnostic algorithm, including the cytogenetic analysis of her karyotype, microarray analysis and methylation­specific MLPA, however, she remained undiagnosed on a molecular level. Therefore, she and her parents were enrolled in the project of trio­based exome sequencing (ES) using Human Core Exome kit. She was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene (NM_000057.4), c.1642C>T and c.2207_2212delinsTAGATTC in the compound heterozygosity, resulting in a diagnosis of Bloom syndrome. Simultaneously, a mosaic loss of heterozygosity of chromosome 11p was detected and then confirmed as a borderline imprinting center 1 hypermethylation on chromosome 11p15. The diagnosis of Bloom syndrome and mosaic copy­number neutral loss of heterozygosity of chromosome 11p increases a lifetime risk to develop any types of malignancy. This case demonstrates the trio­based ES as a complex approach for the molecular diagnostics of rare pediatric diseases.

National Genome Initiatives in Europe and the United Kingdom in the Era of Whole-Genome Sequencing: A Comprehensive Review.

Identification of genomic variability in population plays an important role in the clinical diagnostics of human genetic diseases. Thanks to rapid technological development in the field of massive parallel sequencing technologies, also known as next-generation sequencing (NGS), complex genomic analyses are now easier and cheaper than ever before, which consequently leads to more effective utilization of these techniques in clinical practice. However, interpretation of data from NGS is still challenging due to several issues caused by natural variability of DNA sequences in human populations. Therefore, development and realization of projects focused on description of genetic variability of local population (often called "national or digital genome") with a NGS technique is one of the best approaches to address this problem. The next step of the process is to share such data via publicly available databases. Such databases are important for the interpretation of variants with unknown significance or (likely) pathogenic variants in rare diseases or cancer or generally for identification of pathological variants in a patient's genome. In this paper, we have compiled an overview of published results of local genome sequencing projects from United Kingdom and Europe together with future plans and perspectives for newly announced ones.

Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development.

Pathogenic sequence variant in the GNAI1 gene were recently introduced as a cause of novel syndrome with a manifestation of variable developmental delay and autistic features. In our study, we report a case of monozygotic twins with severe intellectual disability and motor delay and developmental dysphasia. Both probands and their parents were examined using multi-step molecular diagnostic algorithm including whole-exome sequencing (WES), resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815 A>G, p.(Asp272Gly) in probands. Using WES we also verified the microarray findings of a familial 8q24.23q24.3 duplication and heterozygous 5q13.2 deletion, not associated with clinical symptoms in probands. Our results confirmed the role of the GNAI1 gene in the pathogenesis of syndromic neurodevelopmental disorders. They support trio- or quatro-based WES as a suitable molecular diagnostics method for the simultaneous detection of clinically relevant sequence variants and CNVs in individuals with neurodevelopmental disorders and rare diseases.

Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype.

Alport syndrome with intellectual disability (ATS-ID, AMME complex; OMIM #300194) is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by hematuria, renal failure, hearing loss/deafness, neurodevelopmental disorder (NDD), midface retrusion, and elliptocytosis. It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (ACSL4) genes through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide screening of a Czech family with diagnosis ATS-ID (proband, maternal uncle, and two female carriers). Female carriers showed mild clinical features of microscopic hematuria only, while affected males displayed several novel clinical features associated with ATS-ID. Utilization of whole-exome sequencing discovered the presence of approximately 3 Mb of deletion in the Xq23 area, which affected 19 genes from TSC22D3 to CHRDL1. We compared the clinical phenotype with previously reported three ATS-ID families worldwide and correlated their clinical manifestations with the incidence of genes in both telomeric and centromeric regions of the deleted chromosomal area. In addition to previously described phenotypes associated with aberrations in AMMECR1 and FACL4, we identified two genes, members of tripartite motif family MID2 and subunit of the proteasome PA700/19S complex (PSMD10), respectively, as prime candidate genes responsible for additional clinical features observed in our patients with ATS-ID. Overall, our findings further improve the knowledge about the clinical impact of Xq23 deletions and bring novel information about phenotype/genotype association of this chromosomal aberration.

Immunogenicity of the Adjuvanted Recombinant Zoster Vaccine: Persistence and Anamnestic Response to Additional Doses Administered 10 Years After Primary Vaccination.

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years of age. We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule, by following up adults vaccinated at ≥60 years of age and by modeling, and (2) immunogenicity of 2 additional doses administered 10 years after initial vaccination. METHODS: Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10 years after initial vaccination, and modeled through 20 years using a Piecewise, Power law and Fraser model. The immunogenicity and safety of 2 additional RZV doses were also evaluated. RESULTS: Seventy adults were enrolled. Ten years after initial vaccination, humoral and CMI responses were approximately 6-fold and 3.5-fold, respectively, above those before the initial vaccination levels. Predicted immune persistence through 20 years after initial vaccination was similar across the 3 models. Sixty-two participants (mean age [standard deviation], 82.6 [4.4] years) received ≥1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose. CONCLUSIONS: Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10 years after the initial 2-dose course. CLINICAL TRIALS REGISTRATION: NCT02735915.

Molecular Epidemiology of Hantaviruses in the Czech Republic.

During 2008-2018, we collected samples from rodents and patients throughout the Czech Republic and characterized hantavirus isolates. We detected Dobrava-Belgrade and Puumala orthohantaviruses in patients and Dobrava-Belgrade, Tula, and Seewis orthohantaviruses in rodents. Increased knowledge of eco-epidemiology of hantaviruses will improve awareness among physicians and better outcomes of patients.

The clinical benefit of array-based comparative genomic hybridization for detection of copy number variants in Czech children with intellectual disability and developmental delay.

BACKGROUND: Chromosomal microarray analysis has been shown to be a valuable and cost effective assay for elucidating copy number variants (CNVs) in children with intellectual disability and developmental delay (ID/DD). METHODS: In our study, we performed array-based comparative genomic hybridization (array-CGH) analysis using oligonucleotide-based platforms in 542 Czech patients with ID/DD, autism spectrum disorders and multiple congenital abnormalities. Prior to the array-CGH analysis, all the patients were first examined karyotypically using G-banding. The presence of CNVs and their putative derivation was confirmed using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and predominantly relative quantitative polymerase chain reaction (qPCR). RESULTS: In total, 5.9% (32/542) patients were positive for karyotypic abnormalities. Pathogenic/likely pathogenic CNVs were identified in 17.7% of them (96/542), variants of uncertain significance (VOUS) were detected in 4.8% (26/542) and likely benign CNVs in 9.2% of cases (50/542). We identified 6.6% (36/542) patients with known recurrent microdeletion (24 cases) and microduplication (12 cases) syndromes, as well as 4.8% (26/542) patients with non-recurrent rare microdeletions (21 cases) and microduplications (5 cases). In the group of patients with submicroscopic pathogenic/likely pathogenic CNVs (13.3%; 68/510) we identified 91.2% (62/68) patients with one CNV, 5.9% (4/68) patients with two likely independent CNVs and 2.9% (2/68) patients with two CNVs resulting from cryptic unbalanced translocations. Of all detected CNVs, 21% (31/147) had a de novo origin, 51% (75/147) were inherited and 28% (41/147) of unknown origin. In our cohort pathogenic/likely pathogenic microdeletions were more frequent than microduplications (69%; 51/74 vs. 31%; 23/74) ranging in size from 0.395 Mb to 10.676 Mb (microdeletions) and 0.544 Mb to 8.156 Mb (microduplications), but their sizes were not significantly different (P = 0.83). The pathogenic/likely pathogenic CNVs (median 2.663 Mb) were significantly larger than benign CNVs (median 0.394 Mb) (P < 0.00001) and likewise the pathogenic/likely pathogenic CNVs (median 2.663 Mb) were significantly larger in size than VOUS (median 0.469 Mb) (P < 0.00001). CONCLUSIONS: Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics leading to identification of the genetic cause of ID/DD in affected children.

Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant zoster vaccine: a pooled post-hoc analysis of two parallel randomized trials.

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ).Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment.At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant.As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.

Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay.

De novo sequence variants, including truncating and splicing variants, in the additional sex­combs like 3 gene (ASXL3) have been described as the cause of Bainbridge­Ropers syndrome (BRS). This pathology is characterized by delayed psychomotor development, severe intellectual disability, growth delay, hypotonia and facial dimorphism. The present study reports a case of a girl (born in 2013) with severe global developmental delay, central hypotonia, microcephaly and poor speech. The proband was examined using a multi­step molecular diagnostics algorithm, including karyotype and array­comparative genomic hybridization analysis, with negative results. Therefore, the proband and her unaffected parents were enrolled for a pilot study using targeted next­generation sequencing technology (NGS) with gene panel ClearSeq Inherited DiseaseXT and subsequent validation by Sanger sequencing. A novel de novo heterozygous frameshift variant in the ASXL3 gene (c.3006delT, p.R1004Efs*21), predicted to result in a premature termination codon, was identified. In conclusion, the present study demonstrated that targeted NGS using a suitable, gene­rich panel may provide a conclusive molecular genetics diagnosis in children with severe global developmental delays.

Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older.

Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions: Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration: NCT01165177; NCT01165229.

Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults.

BACKGROUND: In adults aged ≥60 years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination. METHODS: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination. RESULTS: Participants' mean age at dose 1 was 72.3 years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing ≥2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, ≥70 years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15. CONCLUSION: In adults aged ≥60 years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination. SUMMARY: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15 years post initial vaccination.

Chromothripsis 18 in multiple myeloma patient with rapid extramedullary relapse.

BACKGROUND: Catastrophic chromosomal event known as chromothripsis was proven to be a significant hallmark of poor prognosis in several cancer diseases. While this phenomenon is very rare in among multiple myeloma (MM) patients, its presence in karyotype is associated with very poor prognosis. CASE PRESENTATION: In our case, we report a 62 year female patient with rapid progression of multiple myeloma (MM) into extramedullary disease and short overall survival (OS = 23 months). I-FISH investigation revealed presence of gain 1q21 and hyperdiploidy (+ 5,+ 9,+ 15) in 82% and 86%, respectively, while IgH rearrangements, del(17)(p13) and del(13)(q14) were evaluated as negative.Whole-genome profiling using array-CGH showed complex genomic changes including hyperdiploidy (+ 3,+ 5,+ 9,+ 11, + 15,+ 19), monosomy X, structural gains (1q21-1q23.1, 1q32-1q44, 16p13.13-16p11.2) and losses (1q23.1-1q32.1; 8p23.3-8p11.21) of genetic material and chromothripsis in chromosome 18 with 6 breakpoint areas. Next-generation sequencing showed a total of 338 variants with 1.8% (6/338) of pathological mutations in NRAS (c.181C > A; p.Gln61Lys) or variants of unknown significance in TP53, CUX1 and POU4F1. CONCLUSIONS: Our findings suggest that presence of chromothripsis should be considered as another important genetic hallmark of poor prognosis in MM patients and utilization of genome-wide screening techniques such as array-CGH and NGS improves the clinical diagnostics of the disease.

Influenza vaccination in the elderly.

Seasonal influenza is a prevalent and serious annual illness resulting in widespread morbidity and economic disruption throughout the population; the elderly and immunocompromised are particularly vulnerable to serious sequelae and mortality. The changing demographics worldwide to an aging society have important implications for public health policy and pharmaceutical innovations. For instance, primary prevention via immunization is effective in reducing the burden of influenza illness among the elderly. However, the elderly may be insufficiently protected by vaccination due to the immunosenescence which accompanies aging. In addition, vaccine hesitancy among the younger populations increases the likelihood of circulating infectious diseases, and thus concomitant exposure. While it is clear that the development of more immunogenic vaccines is an imperative and worthy endeavor, clinical trials continue to demonstrate that the current influenza vaccine formulation remains highly effective in reducing morbidity and mortality when well matched to circulating strains.

Serological survey of mumps antibodies in adults in the Czech Republic and the need for changes to the vaccination strategy.

Mumps outbreaks, especially in adolescents and young adults, have been reported in the Czech Republic. The aim of the presented study was to determine the seroprevalence of specific IgG antibodies against mumps in the adult population of the Czech Republic. The study was designed as a multicenter serological survey of adults aged 18 years and over. Specific IgG antibodies against mumps were detected in blood samples using an enzyme-linked immunosorbent assay (ELISA). A total of 1,911 serum samples were examined. The overall seropositivity reached 55.3%. In individual age groups, the highest seropositivity 63% (63.5-65.2%) was recorded in adults aged 40 years and over; the lowest seropositivity was found in adults aged 18-29 years (27.4%). The difference in seropositivity rate between the 18-29 years age group and the 40 years and over age groups was statistically significant (p < 0.001). Only the 18-29 years age group included both vaccinated and unvaccinated (born in the pre-vaccine era) individuals. In vaccinated individuals, seropositivity was reported in only 19.1% of persons; in unvaccinated individuals, seropositivity reached 48.2%. Our results demonstrate the long-term persistence of antibodies following natural infection and the decrease in seropositivity that occurs after vaccination over time. This immunity waning may account for the higher susceptibility of adolescents and young adults to mumps. Therefore, the current vaccination program in the Czech Republic could be considered as less effective. It will be modified with the shifting of the second dose of vaccine from two years of age to the preschool age.

The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma.

Monoclonal gammopathy of undetermined significance is a pre-malignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little is known about the molecular mechanism of malignant transformation. We performed whole exome sequencing together with comparative genomic hybridization plus single nucleotide polymorphism array analysis in 33 flow-cytometry-separated abnormal plasma cell samples from patients with monoclonal gammopathy of undetermined significance to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in monoclonal gammopathy of undetermined significance than in myeloma (P<10-4) and we identified six genes that were significantly mutated in myeloma (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) within the monoclonal gammopathy of undetermined significance dataset. We also found a positive correlation with increasing chromosome changes and somatic gene mutations. IGH translocations, comprising t(4;14), t(11;14), t(14;16) and t(14;20), were present in 27.3% of cases and in a similar frequency to myeloma, consistent with the primary lesion hypothesis. MYC translocations and TP53 deletions or mutations were not detected in samples from patients with monoclonal gammopathy of undetermined significance, indicating that they may be drivers of progression to myeloma. Data from this study show that monoclonal gammopathy of undetermined significance is genetically similar to myeloma, however overall genetic abnormalities are present at significantly lower levels in monoclonal gammopathy of undetermined significant than in myeloma.

Prevalence of hepatitis C virus in adult population in the Czech Republic - time for birth cohort screening.

Chronic hepatitis C is curable disease. Low detection rate could be one of the reasons of poor treatment uptake. It is important to identify HCV prevalence and anti-hepatitis C virus (HCV) positive patients in population by effective screening strategy such as risk-based or birth cohort screening programs. There are no national population-based estimates of the HCV prevalence in the Czech Republic (CZ). The most recent seroprevalence survey determined a prevalence of positive anti-HCV antibodies of 0.2% (in 2001). The aim of the study was to determine the seroprevalence of HCV, HCV viraemia and HCV genotype in the CZ adult population. We also estimated the number of persons living with chronic hepatitis C in CZ. The examined group included 3000 adults, 18-90 years of age enrolled in 2015. All serum samples were examined to determined anti-HCV antibodies positivity, HCV-RNA positivity and genotypes. Of the 3000 samples, 50 were found to be anti-HCV-positive, for a seroprevalence of 1.67% (2.39% in males, 0.98% in females). The overall prevalence of positive HCV RNA was 0.93%: 1.5% in males, 0.39% in females. HCV genotype (GT) 1a was determined in 25%, GT 1b in 25% and GT 3a in 46%. Since 2001, the HCV seroprevalence has increased 8-fold. The highest HCV seroprevalence occurred in males aged 30-44 years. We can estimate that there are more than 140,000 people with HCV antibodies and more than 80,000 people with chronic hepatitis C living in the CZ. The introduction of birth cohort HCV screening could be beneficial for the country.

Decreasing Seroprevalence of Measles Antibodies after Vaccination - Possible Gap in Measles Protection in Adults in the Czech Republic.

AIMS: In recent years, Europe has recorded an increase in the number of measles outbreaks despite the implementation of vaccination into the National Immunization Programs. The Czech Republic introduced vaccination against measles into National Immunization Program in 1969. The aim of this study was to determine seroprevalence of IgG antibodies against measles in adults. METHODS: Our study was designed as a prospective, multicenter cohort study. Samples of blood were taken from adults aged 18 years and over. Specific IgG antibodies were determined by ELISA method. RESULTS: A number of 1911 sera samples were obtained. The total seropositivity reached 83.3%, 14.3% of the results were negative and 2.4% were borderline. When comparing the individual age groups, the highest antibody seropositivity (> 96%) was detected in persons aged 50 years and over who were naturally infected in pre-vaccine era. The lowest seropositivity was recorded in the age groups 30-39 years (61.5%), 40-49 years (77.5%) and 18-29 years (81.1%). CONCLUSIONS: A long term high rate of seropositivity persists after natural measles infection. By contrast, it decreases over time after vaccination. Similarly, the concentrations of antibodies in persons with measles history persist for a longer time at a higher level than in vaccinated persons. Our results indicate possible gap in measles protection in adults born after implementation of vaccination into the National Immunization Programs. There are two probable reasons, decrease of measles antibody seropositivity in time after vaccination in setting of limited natural booster and one-dose vaccination schedule used in the first years after implementation.