Publications by authors named "Danuta Januszkiewicz-Lewandowska"

65 Publications

A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma.

Cancer Genet 2021 Aug 26;256-257:100-105. Epub 2021 May 26.

Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Szpitalna Street 27/33, 60-572 Poznan, Poland. Electronic address:

IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma. The patient was born at 30 weeks' gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. In the biopsy performed a sarcoma weave with solid, nest-like growth, with characteristics of rhabdomyosarcoma was identified. The family history and physical examination indicated IMAGe syndrome so genetic testing was requested. A whole exome sequencing procedure with use of SureSelectXT Human ALL Exon V7, confirmed a single nucleotide variant NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn); identifying a missense mutation in the imprinted gene CDKN1C associated with IMAGe syndrome. Although tumours associated with CDKN1C are rare, deregulation of imprinted genes is increasingly being recognised as a mechanism of tumorigenesis in cancer; chromosomal region 11p15.5 contains a cluster of imprinted genes. This same region is the most consistent site of allele loss in rhabdomyosarcoma and is the same region altered in both IMAGe and Beckwith-Wiedemann syndrome. Molecular studies have found genetic changes in the 11p15 region in a variety of embryonal tumours like Wilms tumours which are commonly developed in Beckwith-Wiedemann syndrome and embryonal rhabdomyosarcoma. Through this case we aim to present the possibility of oncogenesis in patients with IMAGe syndrome, specifically rhabdomyosarcoma.
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http://dx.doi.org/10.1016/j.cancergen.2021.05.006DOI Listing
August 2021

Arterial constriction after resection of neuroblastic tumors in children: Two-center retrospective study.

J Pediatr Surg 2021 May 8. Epub 2021 May 8.

Department of Pediatric Surgery, Poznan University of Medical Sciences, Poznan, Poland.

Background/purpose: Neuroblastic tumors are the most common pediatric extracranial solid tumors in infants and very young children. Although, especially in newborns, there is an increasing number of situations in which observation alone is used, surgery remains an important step in the treatment of neuroblastoma but can be complicated by arterial vasospasm in the surgical field. The aim of this two-center retrospective study was to analyze the occurrence of arterial constriction as a complication of neuroblastic tumors resection.

Methods: Medical records of patients who were treated surgically for neuroblastic tumors in the years 2012-2019 were reviewed.

Results: For 8 years, 113 children were treated for neuroblastic tumors. The treatment included both primary and delayed surgery after initial chemotherapy carried out according to SIOPEN protocols. In 11 out of 113 cases (9.7%) local arterial constriction was observed. In 6 out of 11 cases an attempt was made to save the organ, however, two patients suffered from kidney atrophy, two other partial kidney infarctions, one child suffered from partial limb paresis, and another from brain ischemia and death.

Conclusions: Local arterial constriction constitutes a relatively common (10% of cases) and severe complication of neuroblastic tumors resection. Efficacy of local application of papaverine based on our experience remains unproven hence further research is warranted.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.04.030DOI Listing
May 2021

The Important Role of the Radiologist in Determining the Indications for the Surgical Treatment of Neuroblastoma with Vascular Image-Defined Risk Factors: A Case Report.

Medicina (Kaunas) 2021 Mar 17;57(3). Epub 2021 Mar 17.

Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Szpitalna Street 27/33, 60-572 Poznan, Poland.

The International Neuroblastoma Risk Group Staging System (INRGSS) is based on the age of patients and preoperative imaging, with attention paid to whether the primary tumor is affected by one or more of specific image-defined risk factors (IDRFs). This publication presents a 2.5-year-old boy with neuroblastoma who had an accidental ligation of the celiac trunk during tumor resection. The consequences of this complication were pancreatic and spleen ischemia and necrosis, ischemia, and perforation of the common bile duct, gallbladder, stomach, and duodenum. The aim of this publication was to highlight the great role of the radiologist in determining the indications for neuroblastoma tumor removal, especially with current vascular IDRFs, and to show how the radiologist's insightful approach can save the patient from irreversible complications.
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http://dx.doi.org/10.3390/medicina57030279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002690PMC
March 2021

The Dramatic Consequences of an Accidental Ligation of the Celiac Trunk during Surgery Performed on a Child with Neuroblastoma.

Int J Environ Res Public Health 2021 02 14;18(4). Epub 2021 Feb 14.

Department of Pediatric Surgery, Traumatology and Urology, Poznan University of Medical Sciences, Szpitalna Street 27/33, 60-572 Poznan, Poland.

Neuroblastoma is the most common extra-cranial solid tumor in infants and young children, and accounts for approximately 8-10% of all childhood cancers. The International Neuroblastoma Staging System (The International Neuroblastoma Risk Group Staging System (INRGSS)) is based on the age of patient and preoperative imaging, with attention paid to whether the primary tumor is affected by one or more of specific Image-Defined Risk Factors (IDRFs). Patients are classified into the following groups: locoregional L1 and L2 (absent or present IDRFs respectively), M stage (a disseminated form of neuroblastoma) and Ms (the stage present in children younger than 18 months of age with the disease spread to the bone marrow and/or liver, and/or skin). This publication is aimed to present an unexpected complication associated with an accidental ligation of the celiac trunk during resection of a neuroblastoma tumor in a 2.5-year-old boy after initial chemotherapy, initially with vascular IDRFs, stage L2. The consequences of this complication were pancreatic and spleen ischemia and necrosis, and ischemia and perforation of the common bile duct, gallbladder, stomach, and duodenum. Despite detailed diagnostic imaging (computed tomography, magnetic resonance), the presence of vascular IDRFs may result in an unexpected complication in the surgical treatment of neuroblastoma in children.
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http://dx.doi.org/10.3390/ijerph18041841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918232PMC
February 2021

Simultaneous Occurrence of Choriocarcinoma in an Infant and Mother.

Int J Environ Res Public Health 2021 02 17;18(4). Epub 2021 Feb 17.

Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, 60-572 Poznań, Poland.

Infantile choriocarcinoma is an extremely rare disease. We present a case study of a 1-month-old male with choriocarcinoma diagnosed simultaneously with his mother. On admission to hospital, the disease was very advanced and massive progression and multi-organ failure caused the death of the patient despite the implemented treatment. It was too late to save the child's life, but early enough to save his mother. The authors believe that the serum levels of hCG should be determined in every newborn with anemia and liver tumor, especially when the mother has a positive history of miscarriage.
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http://dx.doi.org/10.3390/ijerph18041934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922940PMC
February 2021

Knowledge among the rural parents about the vaccinations and vaccination coverage of children in the first year of life in Papua New Guinea - analysis of data provided by Christian health services.

BMC Infect Dis 2021 Jan 30;21(1):130. Epub 2021 Jan 30.

Health Promotion Department, Poznan University of Medical Sciences, Fredry 10, 61-701, Poznan, Poland.

Knowledge among the rural parents about the vaccinations and vaccination coverage of children in the first year of life in Papua New Guinea - analysis of data provided by Christian Health Services.

Background: This analysis aimed to assess rural parents' knowledge about the diseases prevented by vaccinations and establish vaccination coverage in PNG.

Methods: Knowledge of vaccinations was checked through a standard questionnaire (five closed questions). We analyzed data on vaccination coverage from 2016 to 2018 from all Catholic health facilities. Analyzed vaccinations were the pentavalent vaccine (DTaP-HiB-HepB) and measles vaccine given in the first year of life. Coverage was calculated based on the number of vaccines used compared to the number of eligible children. Analyzed vaccinations were the pentavalent vaccine (DTaP-HiB-HepB) and measles vaccine given in the first year of life.

Results: Fifty-six parents, including 52 mothers and four fathers, participated in the interview. Many parents (46%) understood that the vaccine prevents diseases. During the analyzed period, 25,502 doses of measles vaccine were given, 31,428 children were vaccinated with the pentavalent vaccine. In 2016, the measles vaccine coverage rate was 26.6 and 33.4% for the pentavalent vaccine. In 2017, measles and pentavalent vaccines' coverage rate was 12.5 and 16.6%, respectively. There were significant differences in immunization coverage between provinces. A decreasing trend in the number of administered vaccinations was observed.

Conclusion: The results of this analysis demonstrate that in PNG, the majority of children are not fully immunized. There are significant differences in the vaccination coverage between provinces. As protection from diseases is low, there is a very high risk of an outbreak of the vaccine-preventable disease in the community. Delivery of vaccinations in PNG encounters many barriers, from access to healthcare services to natural disasters and inter-tribial conflicts.
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http://dx.doi.org/10.1186/s12879-021-05824-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847142PMC
January 2021

Bilateral Nephroblastoma with Dilated Cardiomyopathy as an Indication for Off-Protocol Treatment: A Case Report.

Int J Environ Res Public Health 2020 12 18;17(24). Epub 2020 Dec 18.

Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 60-572 Poznan, Poland.

Patients with a Wilms tumor are often admitted to the hospital accidentally, with an abdominal mass causing asymmetry of the abdominal wall. Hypertension accompanying a Wilms tumor occurs in about 10-27% of children, but cardiomyopathy associated with a Wilms tumor is very rarely described. This publication presents a case of a 9-month-old girl with a bilateral Wilms tumor accompanied by dilated cardiomyopathy since her initial cancer diagnosis, as well as her off-protocol treatment. The severe condition of the child forced the application of off-protocol treatment, i.e., accelerated resection of a larger tumor, which enabled the improvement of heart performance and made subsequent therapy possible. In the course of the presented treatment, a gradual normalization of cardiac ventricular function and contractility was observed. In conclusion, a massive abdominal tumor associated with abdominal compartment syndrome compromised the functioning of the cardiovascular system in the young child. Therefore, earlier removal of Wilms tumors in patients with heart failure should be considered. This may result in the improvement of cardiovascular function and the possibility of further therapy.
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http://dx.doi.org/10.3390/ijerph17249483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766981PMC
December 2020

Pediatric Inflammatory Multisystem Syndrome (PIMS) Did Occur in Poland during Months with Low COVID-19 Prevalence, Preliminary Results of a Nationwide Register.

J Clin Med 2020 10 22;9(11). Epub 2020 Oct 22.

Department of Pediatrics with Clinical Decisions Unit, Medical University of Warsaw, Żwirki i Wigury 63A, 02-091 Warsaw, Poland.

Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19) infection. Most of the reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On 25 May 2020, we launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4 March 2020) and prospective data collection. Up to 28 July, 39 reported children met the inclusion criteria. We stratified them according to age (<5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and nine children had COVID-19 confirmation. This is, to our knowledge, the first report of the PIMS register from a country with a low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g., older age, should be considered in the differential diagnosis of inflammatory syndromes in children.
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http://dx.doi.org/10.3390/jcm9113386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690437PMC
October 2020

The Profile of Microorganisms Responsible for Port-Related Bacteremia in Pediatric Hemato-Oncological Patients.

Cancer Control 2020 Jan-Dec;27(1):1073274820904696

Department of Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland.

Patients with pediatric cancer face an increased risk of infections. In most cases, these infections are associated with the use of a long-term central venous catheter. This study describes the epidemiology of a port-associated bacteremia as well as a profile of microorganisms responsible for port-associated bloodstream infections (PABSIs) in pediatric patients with cancer treated in a single center. The retrospective analysis included patients with cancer who had implanted a port, hospitalized between 2010 and 2015 at the Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences. The medical records of patients were reviewed for demographic characteristics, diagnosis, port-related complications, and their management. Data were collected from patients' electronic medical records containing complete information on medical examinations and supplementary tests, diagnosis, timing, and type of port-associated complications. In a study period, 277 ports were inserted to 241 patients. A total of 183 094 catheter days were analyzed. Sixteen patients had more than 1 insertion of a port. The commonest observed complication was PABSI (40.07%) and the incidence density was 0.6 per 1000 port-days. was the most commonly isolated organisms from patients with PABSI. From all port-associated complications, bloodstream infections and mechanical complications were the most often observed complications. The commonest pathogens responsible for PABSI were coagulase-negative staphylococci. Pathogens resistant to standard antibiotic treatment play an important role in PABSI, with methicillin-resistant being the predominant pathogen. Port-associated bloodstream infections are a common reason for preterm removal of a port.
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http://dx.doi.org/10.1177/1073274820904696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092702PMC
October 2020

A genome-wide association study on medulloblastoma.

J Neurooncol 2020 Apr 13;147(2):309-315. Epub 2020 Feb 13.

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.

Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.

Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10), but none were statistically significant after adjusting for multiple testing (p < 5 × 10). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (OR = 1.59, p = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, OR = 3.76, p = 3.2 × 10) and rs79036813 (PTCH1, OR = 0.42, p = 2.6 × 10).

Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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http://dx.doi.org/10.1007/s11060-020-03424-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136185PMC
April 2020

Paediatric hospitalisation numbers for influenza in 2016-2019 seasons underline importance of vaccination.

Acta Paediatr 2020 02 27;109(2):417-418. Epub 2019 Oct 27.

Department of Oncology - Hematology and Bone Marrow Transplantation Poznan, Poznan University of Medical Science, Poznan, Poland.

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http://dx.doi.org/10.1111/apa.15055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004104PMC
February 2020

Repertoire Sequencing of B Cells Elucidates the Role of UNG and Mismatch Repair Proteins in Somatic Hypermutation in Humans.

Front Immunol 2019 27;10:1913. Epub 2019 Aug 27.

Laboratory for Immunology, Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.

The generation of high-affinity antibodies depends on somatic hypermutation (SHM). SHM is initiated by the activation-induced cytidine deaminase (AID), which generates uracil (U) lesions in the B-cell receptor (BCR) encoding genes. Error-prone processing of U lesions creates a typical spectrum of point mutations during SHM. The aim of this study was to determine the molecular mechanism of SHM in humans; currently available knowledge is limited by the number of mutations analyzed per patient. We collected a unique cohort of 10 well-defined patients with bi-allelic mutations in genes involved in base excision repair (BER) () or mismatch repair (MMR) (, or ) and are the first to present next-generation sequencing (NGS) data of the BCR, allowing us to study SHM extensively in humans. Analysis using ARGalaxy revealed selective skewing of SHM mutation patterns specific for each genetic defect, which are in line with the five-pathway model of SHM that was recently proposed based on mice data. However, trans-species comparison revealed differences in the role of PMS2 and MSH2 in strand targeting between mice and man. In conclusion, our results indicate a role for UNG, MSH2, MSH6, and PMS2 in the generation of SHM in humans comparable to their function in mice. However, we observed differences in strand targeting between humans and mice, emphasizing the importance of studying molecular mechanisms in a human setting. The here developed method combining NGS and ARGalaxy analysis of BCR mutation data forms the basis for efficient SHM analyses of other immune deficiencies.
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http://dx.doi.org/10.3389/fimmu.2019.01913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718458PMC
October 2020

High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers.

J Med Genet 2020 04 7;57(4):269-273. Epub 2019 Sep 7.

Hereditary Cancer Program, Catalan Institute of Oncology - ICO, Hereditary Cancer Group, Molecular Mechanisms and Experimental Therapy in Oncology Program, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, Ciber Oncología (CIBERONC) - Instituto de Salud Carlos III, L'Hospitalet de Llobregat, Barcelona, Spain.

Introduction: Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are hereditary cancer syndromes associated with mismatch repair (MMR) deficiency. Tumours show microsatellite instability (MSI), also reported at low levels in non-neoplastic tissues. Our aim was to evaluate the performance of high-sensitivity MSI (hs-MSI) assessment for the identification of LS and CMMRD in non-neoplastic tissues.

Materials And Methods: Blood DNA samples from 131 individuals were grouped into three cohorts: baseline (22 controls), training (11 CMMRD, 48 LS and 15 controls) and validation (18 CMMRD and 18 controls). Custom next generation sequencing panel and bioinformatics pipeline were used to detect insertions and deletions in microsatellite markers. An hs-MSI score was calculated representing the percentage of unstable markers.

Results: The hs-MSI score was significantly higher in CMMRD blood samples when compared with controls in the training cohort (p<0.001). This finding was confirmed in the validation set, reaching 100% specificity and sensitivity. Higher hs-MSI scores were detected in biallelic carriers (n=5) compared with carriers (n=15). The hs-MSI analysis did not detect a difference between LS and control blood samples (p=0.564).

Conclusions: The hs-MSI approach is a valuable tool for CMMRD diagnosis, especially in suspected patients harbouring MMR variants of unknown significance or non-detected biallelic germline mutations.
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http://dx.doi.org/10.1136/jmedgenet-2019-106272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146943PMC
April 2020

A sensitive and scalable microsatellite instability assay to diagnose constitutional mismatch repair deficiency by sequencing of peripheral blood leukocytes.

Hum Mutat 2019 05 6;40(5):649-655. Epub 2019 Mar 6.

Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.

Constitutional mismatch repair deficiency (CMMRD) is caused by germline pathogenic variants in both alleles of a mismatch repair gene. Patients have an exceptionally high risk of numerous pediatric malignancies and benefit from surveillance and adjusted treatment. The diversity of its manifestation, and ambiguous genotyping results, particularly from PMS2, can complicate diagnosis and preclude timely patient management. Assessment of low-level microsatellite instability in nonneoplastic tissues can detect CMMRD, but current techniques are laborious or of limited sensitivity. Here, we present a simple, scalable CMMRD diagnostic assay. It uses sequencing and molecular barcodes to detect low-frequency microsatellite variants in peripheral blood leukocytes and classifies samples using variant frequencies. We tested 30 samples from 26 genetically-confirmed CMMRD patients, and samples from 94 controls and 40 Lynch syndrome patients. All samples were correctly classified, except one from a CMMRD patient recovering from aplasia. However, additional samples from this same patient tested positive for CMMRD. The assay also confirmed CMMRD in six suspected patients. The assay is suitable for both rapid CMMRD diagnosis within clinical decision windows and scalable screening of at-risk populations. Its deployment will improve patient care, and better define the prevalence and phenotype of this likely underreported cancer syndrome.
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http://dx.doi.org/10.1002/humu.23721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519362PMC
May 2019

No Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency.

Front Immunol 2018 2;9:1506. Epub 2018 Jul 2.

Research Unit Pediatric Hematology and Immunology, Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.

Immunoglobulin class-switch recombination (CSR) and somatic hypermutations (SHMs) are prerequisites for antibody and immunoglobulin receptor maturation and adaptive immune diversity. The mismatch repair (MMR) machinery, consisting of homologs of MutSα, MutLα, and MutSβ (MSH2/MSH6, MLH1/PMS2, and MSH2/MSH3, respectively) and other proteins, is involved in CSR, primarily acting as a backup for nonhomologous end-joining repair of activation-induced cytidine deaminase-induced DNA mismatches and, furthermore, in addition to error-prone polymerases, in the repair of SHM-induced DNA breaks. A varying degree of antibody formation defect, from IgA or selective IgG subclass deficiency to common variable immunodeficiency and hyper-IgM syndrome, has been detected in a small number of patients with constitutional mismatch repair deficiency (CMMRD) due to biallelic loss-of-function mutations in one of the MMR genes (). To elucidate the clinical relevance of a presumed primary immunodeficiency (PID) in CMMRD, we systematically collected clinical history and laboratory data of a cohort of 15 consecutive, unrelated patients (10 not previously reported) with homozygous/compound heterozygous mutations in ( = 8), ( = 5), and ( = 2), most of whom manifested with typical malignancies during childhood. Detailed descriptions of their genotypes, phenotypes, and family histories are provided. Importantly, none of the patients showed any clinical warning signs of PID (infections, immune dysregulation, inflammation, failure to thrive, etc.). Furthermore, we could not detect uniform or specific patterns of laboratory abnormalities. The concentration of IgM was increased in 3 out of 12, reduced in 3 out of 12, and normal in 6 out of 12 patients, while concentrations of IgG and IgG subclasses, except IgG4, and of IgA, and specific antibody formation were normal in most. Class-switched B memory cells were reduced in 5 out of 12 patients, and in 9 out of 12 also the CD38IgM plasmablasts were reduced. Furthermore, results of next generation sequencing-based analyses of antigen-selected B-cell receptor rearrangements showed a significantly reduced frequency of SHM and an increased number of rearranged immunoglobulin heavy chain (IGH) transcripts that use IGHG3, IGHG1, and IGHA1 subclasses. T cell subsets and receptor repertoires were unaffected. Together, neither clinical nor routine immunological laboratory parameters were consistently suggestive of PID in these CMMRD patients, but previously shown abnormalities in SHM and rearranged heavy chain transcripts were confirmed.
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http://dx.doi.org/10.3389/fimmu.2018.01506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036136PMC
July 2018

Rhabdomyosarcoma in children - current pathologic and molecular classification.

Pol J Pathol 2018;69(1):20-32

The last 25 years have brought significant progress in the treatment of sarcomas in children, especially rhabdomyosarcoma (RMS). Nevertheless, treatment failure in some patients results from considerable biological heterogeneity noted in these tumours. RMS, the most common malignant soft tissue neoplasm in children, includes two main subtypes: embryonal (ERMS) and alveolar (ARMS). Due to greater aggressiveness and worse prognosis of ARMS in comparison to ERMS, discrimination between different rhabdomyosarcoma subtypes is of crucial clinical importance. This paper presents the current histological classification of RMS, up-to-date immunohistochemical and biological research regarding RMS, and its associated clinical and prognostic significance.
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http://dx.doi.org/10.5114/pjp.2018.75333DOI Listing
July 2018

Genes and their single nucleotide polymorphism involved in innate immune response in central nervous system in bacterial meningitis: review of literature data.

Inflamm Res 2018 Aug 12;67(8):655-661. Epub 2018 May 12.

Department of Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.

Background: There are many studies analysing the effect of SNPs in genes coding proteins which are involved in innate immune response on susceptibility to invasive bacterial disease. Many of them gave inconclusive results. Regarding the complexity of immune response and cooperation between particular elements, number of SNPs may have a cumulative effect on the susceptibility to bacterial meningitis.

Findings: In most studies cooccurrence of several SNPs was not analysed. These studies were performed on small groups of patients and usually only few SNPs were checked simultaneously. Additionally, comparison of the results across the studies is hard to conduct. We hypothesise that the number of variants of genes involved in innate immune response plays a role in susceptibility to bacterial meningitis. However, the role of toll-like receptors and other part of innate immune response in the eradication of bacteria, and initiation of the inflammatory response in CNS need further studies.

Conclusion: Large multicentre studies assessing multiple SNPs in patients with microbiologically proven pneumococcal or meningococcal meningitis are needed to find real genetic risk factors for developing bacterial meningitis. This is necessary to design more effective treatment and prevention strategies for severe infections.
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http://dx.doi.org/10.1007/s00011-018-1158-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028835PMC
August 2018

How many single-nucleotide polymorphisms (SNPs) must be tested in order to prove susceptibility to bacterial meningitis in children? Analysis of 11 SNPs in seven genes involved in the immune response and their effect on the susceptibility to bacterial meningitis in children.

Innate Immun 2018 04 13;24(3):163-170. Epub 2018 Mar 13.

2 Institute of Human Genetics, Polish Academy of Sciences, Poznan Poland.

The aim of this study is to describe the prevalence of single single-nucleotide polymorphisms (SNPs) as well as their combinations in genes encoding proteins involved in the immune response in children with bacterial meningitis. The prospective study group consisted of 39 children with bacterial meningitis and 49 family members surveyed between 2012 and 2016. Eleven SNPs in seven genes involved in immune response were analysed. The mean number of minor frequency alleles (MAF) of studied SNPs was lowest in the control group and highest in patients with pneumococcal meningitis. We found that carrying ≥6 MAF of studied SNPs was associated with an increased risk of pneumococcal meningitis. The prevalence of risky variants was noted to be higher in patients with pneumococcal meningitis as compared to the control group. In conclusion, genetic factors are a relevant factor in determining the susceptibility to bacterial meningitis. A statistically significant cumulative effect of mutated variants on increasing the risk of bacterial meningitis was detected. Combining all three SNPs in MBL2 improves the prediction of susceptibility to pneumococcal meningitis. Analysis of risky alleles can help indicate people prone to the disease who are 'gene-immunocompromised'.
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http://dx.doi.org/10.1177/1753425918762038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852385PMC
April 2018

Imatinib in the treatment of chronic myeloid leukemia in children and adolescents is effective and well tolerated: Report of the Polish Pediatric Study Group for the Treatment of Leukemias and Lymphomas.

Adv Clin Exp Med 2018 Jan;27(1):91-98

Department and Clinic of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Poland.

Background: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children.

Objectives: The objective of this study is to evaluate treatment with imatinib in Polish pediatric patients with CML.

Material And Methods: We analyzed the results of treatment with imatinib in 57 pediatric patients (June 2006 - January 2016) from 14 Polish pediatric hematology and oncology centers.

Results: In the study group, 40 patients continued imatinib (median follow-up: 23.4 months), while in 17 the treatment was terminated (median follow-up: 15.1 months) due to therapy failure. In the latter group, 13 patients underwent HSCT, while 4 switched to second-generation TKIs. The 5-year overall survival rate (OS) in the study group was 96%, and the 5-year event-free survival (EFS) was 81%.

Conclusions: Our results confirm that the introduction of TKI therapy has revolutionized the treatment of CML in the pediatric population by replacing the previous method of treatment with HSCT and allowing a high percentage of OS and EFS.
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http://dx.doi.org/10.17219/acem/66462DOI Listing
January 2018

The methylenetetrahydrofolate reductase 677T-1298C haplotype is a risk factor for acute lymphoblastic leukemia in children.

Medicine (Baltimore) 2017 Dec;96(51):e9290

Institute of Human Genetics, Polish Academy of Sciences Department of Internal and Vascular Surgery, Poznan University of Medical Sciences, Laboratory for Basic Research and Translational Medicine Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences Department of Family Medicine, Poznan University of Medical Sciences Department of Medical Diagnostics, Poznan, Poland.

The etiology of acute lymphoblastic leukemia (ALL) is complex, linked with both environmental exposures and genetic factors. Functional variants of the methylenetetrahydrofolate reductase (MTHFR) gene result in disturbance in folate metabolism and may affect susceptibility to cancer. The study was performed to evaluate whether MTHFR C677T and A1298C polymorphisms, analyzed separately and together, are associated with the development of ALL in a population under 18 years of age of Caucasian ancestry.The study included 117 pediatric patients (59% males, mean age at diagnosis 7.4 ± 5.2 years) with ALL, confirmed by conventional immunophenotyping surface-marker analysis and 404 healthy control subjects (48.5% men, mean age 37.7 ± 11.3 years). The MTHFR C677T and A1298C genotypes were analyzed using allele discrimination tests with Taq-Man fluorescent probes.The MTHFR 677TT genotype was related to a 2-fold increase in risk of ALL (P = .014). The 677T-1298C haplotype was found in ALL patients but not in controls (frequency 0.598%; P <.0001). The observed frequency of carriers of this rare haplotype was 12%, including 677CT/1298CC (1.7%), 677TT/1298AC (6.0%), and 677CT/1298AC (4.3%) genotypes.The MTHFR 677T allele alone or in combination with the MTHFR 1298C allele significantly increases the risk of development of ALL in Polish population under 18 years of age. Further studies of haplotype composition in subjects with the 677CT/1298AC genotype are necessary to assess the risk of childhood ALL.
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http://dx.doi.org/10.1097/MD.0000000000009290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758194PMC
December 2017

Distribution of polymorphisms rs12979860, rs8099917 and rs12980275 IL28B in patients with chronic hepatitis C.

Adv Clin Exp Med 2017 Nov;26(8):1257-1261

Department of Molecular Pathology, Institute of Human Genetics PASc, Poznań, Poland.

Background: The prognosis concerning the treatment of patients with chronic hepatitis C (CHC) is closely related to the genotype of the virus as well as to the factors dependent on the patient. It was proved that polymorphisms of the gene encoding interleukin 28B (IL28B) are associated with sustained viral response, which in the case of profitable variants of IL28B polymorphisms may reach up to 87% of the patients.

Objectives: The aim of the study is to determine the prevalence of alleles and distribution of IL28B polymorphisms genotypes in the examined group of patients with CHC in Wielkopolska Province.

Material And Methods: A total of 710 people with diagnosed hepatitis C virus were examined in order to determine the distribution of polymorphisms of gene IL28B rs12979860, rs8099917 and rs12980275. The polymorphisms were evaluated by sequencing of PCR products.

Results: The most often noted profitable variant was genotype TT for polymorphism rs8099917 present in 43.5% of the patients, next was AA rs12980275 in 22.5%. The rarest was the profitable variant CC of the polymorphism rs12979860 present in 17.5% of the patients. An occurrence of at least 2 IL28B polymorphisms in the preferred variants (homozygote CC, TT, AA) was found in 239 out of 710 (34%) patients, among which 117 patients had favorable genotypes for all 3 examined polymorphisms.

Conclusions: The SNP distribution of gene IL28 with fixed prognostic value in the population of patients with chronic hepatitis C is different from the general population, and shows the need to evaluate polymorphisms prior to treatment.
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http://dx.doi.org/10.17219/acem/66076DOI Listing
November 2017

With a little help from a computer: discriminating between bacterial and viral meningitis based on dominance-based rough set approach analysis.

Medicine (Baltimore) 2017 Aug;96(32):e7635

Department of Family Medicine Department of Oncology, Hematology and Bone Marrow Transplantation Department of Molecular Pathology, Institute of Human Genetics Polish Academy of Sciences Department of Medical Diagnostics Institute of Computing Science, Poznań University of Technology Department of Biostatistics Department of Health Promotion, Poznań University of Medical Sciences, Poznań, Poland.

Differential Diagnosis of bacterial and viral meningitis remains an important clinical problem. A number of methods to assist in the diagnoses of meningitis have been developed, but none of them have been found to have high specificity with 100% sensitivity.We conducted a retrospective analysis of the medical records of 148 children hospitalized in St. Joseph Children's Hospital in Poznań. In this study, we applied for the first time the original methodology of dominance-based rough set approach (DRSA) to diagnostic patterns of meningitis data and represented them by decision rules useful in discriminating between bacterial and viral meningitis. The induction algorithm is called VC-DomLEM; it has been implemented as software package called jMAF (http://www.cs.put.poznan.pl/jblaszczynski/Site/jRS.html), based on java Rough Set (jRS) library.In the studied group, there were 148 patients (78 boys and 70 girls), and the mean age was 85 months. We analyzed 14 attributes, of which only 4 were used to generate the 6 rules, with C-reactive protein (CRP) being the most valuable.Factors associated with bacterial meningitis were: CRP level ≥86 mg/L, number of leukocytes in cerebrospinal fluid (CSF) ≥4481 μL, symptoms duration no longer than 2 days, or age less than 1 month. Factors associated with viral meningitis were CRP level not higher than 19 mg/L, or CRP level not higher than 84 mg/L in a patient older than 11 months with no more than 1100 μL leukocytes in CSF.We established the minimum set of attributes significant for classification of patients with meningitis. This is new set of rules, which, although intuitively anticipated by some clinicians, has not been formally demonstrated until now.
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http://dx.doi.org/10.1097/MD.0000000000007635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556211PMC
August 2017

Too young to be vaccinated: hospitalizations caused by varicella among children in the first year of life.

Int J Infect Dis 2017 Sep 19;62:52-55. Epub 2017 Jul 19.

Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; Department of Oncology, Haematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.

Aim: The aim of this study was to analyse the causes of hospitalization in the course of varicella in children during the first year of life.

Methods: An analysis was performed of the medical documentation of 359 children hospitalized for varicella on the infectious diseases ward at the Children's Hospital in Poznan (Poland) between January 2007 and August 2015.

Results: Of the 359 children in the study group, 96 were younger than 1 year old. The most common cause of hospitalization was respiratory infections, found in 31 (32%) children. A severe course of varicella was observed in 38 (14%) children, and 21 (22%) developed skin infections, while 11 (11%) exhibited more than one complication. Treatment with acyclovir was implemented in 90 cases and parenteral antibiotic therapy was applied in 49 children. Contact with siblings suffering from varicella was confirmed in 46 children; for 16, the source of the infection was the mother.

Conclusions: The main source of varicella virus among hospitalized children in the first year of life is home contact. An infant may become infected from its mother suffering from zoster. Children who are exclusively breastfed and are born of mothers who have previously had varicella may develop varicella with a severe course during the first year of life.
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http://dx.doi.org/10.1016/j.ijid.2017.07.009DOI Listing
September 2017

Prevalence of rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C.

World J Gastroenterol 2017 Jun;23(21):3815-3824

Bogna Świątek-Kościelna, Ewelina Kałużna, Ewa Strauss, Jerzy Nowak, Jolanta Rembowska, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland, 60-479 Poznan, Poland.

Aim: To evaluate the association of () SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C (CHC).

Methods: The study enrolled 196 CHC Polish patients (82 women and 114 men in age 20-64) infected with hepatitis C virus (HCV) genotype 1. They were treatment naïve and qualified to pegylated interferon alpha (PEG-IFN-α) and ribavirin (RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase (ALT), asparagine aminotransferase (AST) and total bilirubin (TBIL). The analysis of response to therapy included: sustained virological response (SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms (SNPs) (rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons.

Results: Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC (grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217C allele is associated with SVR (C A: < 0.0001; dose of C allele: = 0.0002) and non-relapse (C A: = 0.001; dose of C allele: = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients ( < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment ( = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR ( = 0.016) and relapse ( = 0.024).

Conclusion: The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-α and RBV.
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http://dx.doi.org/10.3748/wjg.v23.i21.3815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467067PMC
June 2017

Analysis of TLR2, TLR4, and TLR9 single nucleotide polymorphisms in children with bacterial meningitis and their healthy family members.

Int J Infect Dis 2017 Jul 6;60:23-28. Epub 2017 May 6.

Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland; Department of Oncology, Haematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.

Background: The aim was to analyse TLR2 rs5743708, TLR2 rs4696480, TLR4 rs4986790, TLR9 rs5743836, and TLR9 rs352140 single nucleotide polymorphisms (SNPs) in children with pneumococcal and meningococcal meningitis and their family members.

Methods: The study group consisted of 39 children with bacterial meningitis (25 with meningococcal meningitis and 14 with pneumococcal meningitis) and 49 family members. Laboratory test results and the course of the diseases were analyzed. Genomic DNA was extracted from 1.2ml of peripheral blood in order to analyze the five SNPs.

Results: Patients with pneumococcal and meningococcal meningitis showed a similar male/female ratio, mean age, and duration of symptoms. There were no statistically significant differences in biochemical markers between the two groups. All patients possessed at least one polymorphic variant of the analyzed SNPs. The most common SNP was TLR9 rs352140, detected in 89.7% of patients. No significant differences in SNP frequency were found between patients, family members, and the general population.

Conclusions: The allele frequencies in the population studied are in accordance with the literature data. The study did not find an association between the analyzed SNPs and susceptibility to bacterial meningitis. The role of SNPs in genes coding toll-like receptors and the interactions between them in controlling inflammation in the central nervous system needs further evaluation.
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http://dx.doi.org/10.1016/j.ijid.2017.04.024DOI Listing
July 2017

Effect of irradiation on DNA synthesis, gene expression and chromosomal stability in cells with mutations.

Arch Med Sci 2017 Mar 25;13(2):283-292. Epub 2017 Jan 25.

Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; Department of Paediatric Oncology, Haematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.

Introduction: The gene product is part of the MRE11/RAD50/NBN complex, which plays an essential role in genomic stability. In the study we try to answer the question what is the effect of irradiation on DNA synthesis, gene expression and chromosomal stability in cells with homozygous c.657-661del, and heterozygous c.657-661del, p.I171V and p.R215W gene mutations.

Material And Methods: Immortalized B-lymphocytes with gene mutations were X-ray irradiated at doses of 1, 2, 5 and 8 Gy/min. Radioresistant DNA synthesis rate and the percentage of cells in phase S was analyzed by H thymidine and BrdU incorporation assays. gene expression was quantified by real-time PCR with TaqMan fluorescent probe.

Results: Increasing the irradiation dose resulted in gradual decrease of H thymidine incorporation in all cells, but significantly only in homo- and heterozygous c.657-661del cells (-values < 0.0001). After irradiation the relative expression of was significantly higher in homozygous c.657-661del and heterozygous p.R215W cells as compared to heterozygous c.657-661del, p.I171V and control cells ( < 0.01). All cells with gene mutations showed significantly higher total number of chromosomal aberrations per metaphase as compared to control cells, with the highest number of aberrations in homozygous c.657-661del cells ( < 0.001).

Conclusions: The results obtained indicate that homozygous c.657-661del mutation affects cell sensitivity to irradiation. Moreover, homozygous variant is associated with disturbance in the activation of cell cycle checkpoints and with defects in DNA repair. In turn, heterozygous c.657-661del, p.R215W and p.I171V mutations do not substantially alter the radiosensitivity.
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http://dx.doi.org/10.5114/aoms.2017.65452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332466PMC
March 2017

Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience.

Biomed Res Int 2017 15;2017:8037963. Epub 2017 Jan 15.

Department of Medical Diagnostics, University of Medical Sciences, Dobra 38, Poznan, Poland; Department of Paediatric Oncology, Hematology and Bone Marrow Transplantation, University of Medical Sciences, Poznan, Poland; Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.

The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. . The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. . Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. . Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations.
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http://dx.doi.org/10.1155/2017/8037963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5274672PMC
February 2017

FKBP5 polymorphism is associated with insulin resistance in children and adolescents with obesity.

Obes Res Clin Pract 2018 Jan - Feb;12(Suppl 2):62-70. Epub 2016 Dec 20.

Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, 27/33 Szpitalna, 60-572 Poznan, Poland.

Objective: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis. We investigated the association of rs1360780 with obesity and metabolic characteristics in 250 obese children and adolescents (mean age 12.3±3.6years, BMI ≥95th percentile).

Methods: Anthropometric measurements, body composition, biochemical and hormonal results were analysed. Genotyping of rs1360780 was compared with 568 lean controls.

Results: Impaired fasting glucose was present in 8.8%, glucose intolerance in 10.4%, diabetes in 2.8% and dyslipidemia in 28.8% obese individuals. Hypertension was diagnosed in 34 out of 143 patients. No difference was found in FKBP5 polymorphism distribution between subjects with obesity and controls (p>0.05). Stratification by rs1360780 revealed no differences in body mass and composition. However, carriers of the minor allele displayed enhanced insulin resistance (p=0.009) and elevated serum triglyceride (p=0.006), whereas cholesterol, HbA1c, and oral glucose challenge results were similar for all genotypes. Morning ACTH and cortisol did not differ but evening cortisol was higher in minor allele carriers (p=0.039), although this association was lost in logistic regression analysis.

Conclusion: This study does not support the association of FKBP5 with obesity but demonstrates plausible implication of its variant in susceptibility to obesity-related insulin resistance and hypertriglyceridemia.
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http://dx.doi.org/10.1016/j.orcp.2016.11.007DOI Listing
April 2019

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children: A cross-sectional study.

Medicine (Baltimore) 2016 Dec;95(49):e5571

Family Medicine Department Department of Health Promotion, Poznan University of Medical Sciences Institute of Human Genetics Polish Academy of Sciences, Department of Molecular Pathology Department of Medical Diagnostic Dobra Department of Biostatistics, Poznan University of Medical Sciences Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.

Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children.Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule.Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection.Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies.The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The decrease in antibody titers occurring over time is a significant factor in vaccination program planning.Tetanus antibody concentrations were found to be high, but responses to the diphtheria and tetanus components were divergent. The percentage of children protected against diphtheria was significantly lower than protected against tetanus.
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http://dx.doi.org/10.1097/MD.0000000000005571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266040PMC
December 2016

Interleukin 10 gene single nucleotide polymorphisms in Polish patients with chronic hepatitis C: Analysis of association with severity of disease and treatment outcome.

Hum Immunol 2017 Feb 26;78(2):192-200. Epub 2016 Oct 26.

Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland.

It is suggested that interleukin 10 (IL-10), as a modulator of immune response, is likely to influence the elimination of hepatitis C virus (HCV), the progression of chronic hepatitis C (CHC) and the response to interferon-based therapy in CHC patients. The aim of the study was to analyze the association of single nucleotide polymorphisms (SNPs) of IL-10 gene with severity of liver disease (degree of inflammation and stage of fibrosis) and outcome of pegylated interferon alpha and ribavirin combined therapy (sustained virological response (SVR) and relapse) in 196 Polish CHC patients infected with HCV genotype 1. The analysis included IL-10 promoter SNPs: -1082(A/G) rs1800896, -819(C/T) rs1800871, -592(C/A) rs1800872 and SNP in the 3' UTR of IL-10 gene: +4529(A/G) rs3024498. Genotyping was performed using PCR-RFLP and HRM analysis. It was demonstrated that the -592C allele is associated with mild hepatic inflammation. Moreover, it was found that the -819C allele might be associated with SVR and that the ACCA haplotype and intermediate IL-10 producer ACC haplotype are associated with SVR and non-relapse. It can be concluded that IL-10 SNPs are associated with severity of disease and response to therapy and may be considered as potential prognostic and predictive markers in CHC.
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http://dx.doi.org/10.1016/j.humimm.2016.10.015DOI Listing
February 2017
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