Polygenic Risk Score Predicts Modified Risk in BRCA1 Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients.

The aim of this study was to assess the power of the polygenic risk score (PRS) in estimating the overall genetic risk of women carrying germline BRCA1 pathogenic variants (PVs) c.4035del or c.5266dup to develop breast (BC) or ovarian cancer (OC) due to additional genetic variations. In this study, PRSs previously developed from two joint models using summary statistics of age-at-onset (BayesW model) and case-control data (BayesRR-RC model) from a genome-wide association analysis (GWAS) were applied to 406 germline BRCA1 PV (c.4035del or c.5266dup) carriers affected by BC or OC, compared with unaffected individuals. A binomial logistic regression model was used to assess the association of PRS with BC or OC development risk. We observed that the best-fitting BayesW PRS model effectively predicted the individual's BC risk (OR = 1.37; 95% CI = 1.03-1.81, p = 0.02905 with AUC = 0.759). However, none of the applied PRS models was a good predictor of OC risk. The best-fitted PRS model (BayesW) contributed to assessing the risk of developing BC for germline BRCA1 PV (c.4035del or c.5266dup) carriers and may facilitate more precise and timely patient stratification and decision-making to improve the current BC treatment or even prevention strategies.

Correction: Effectiveness of Secondary Risk-Reducing Strategies in Patients With Unilateral Breast Cancer With Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery: Evidence-Based Simulation Study.

[This corrects the article DOI: .].

Effectiveness of Secondary Risk-Reducing Strategies in Patients With Unilateral Breast Cancer With Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery: Evidence-Based Simulation Study.

BACKGROUND: Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. OBJECTIVE: The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. METHODS: We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk-reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. RESULTS: Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk-reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. CONCLUSIONS: Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.

Prevalence of Aeromonas spp. Infection in Pediatric Patients Hospitalized with Gastroenteritis in Latvia between 2020 and 2021.

PURPOSE: Aeromonas species are emerging human enteric pathogens. However, there is no systematic analysis of Aeromonas infection in the pediatric population in Latvia. The aim of the study was to describe potential sources, prevalence of infection, associated virulence factors and antimicrobial resistance of Aeromonas spp. isolated from fecal samples. METHODS: Stool samples (n = 1360) were obtained from the Children's Clinical University Hospital between 2020 and 2021. The target population was pediatric patients, 0 to 18 years of age, with a preliminary diagnosis of gastroenteritis. Identification was performed by Maldi-TOF, antimicrobial resistance by Vitek2 and 9 virulence factors by polymerase chain reaction (PCR). RESULTS: Aeromonas spp. were isolated in 50 stool samples; positive findings made up 3.6% of all study cases and included four species: A. hydrophila, A. caviae, A. veronii, and A. eucrenophila. In 42% of the samples, Aeromonas spp. appeared alongside the other significant pathogens: Campylobacter jejuni, Salmonella Enteritidis, Salmonella Typhimurium, Yersinia enterocolitica, norovirus, adenovirus, and rotavirus. The study population positive for Aeromonas spp. infection contained 28 male (56%) and 22 female (44%) patients; median age was 4.56 years. The most common symptoms were: diarrhea, blood in stool, vomiting, abdominal pain, and fever. Aside from expected natural resistance, no significant antibacterial resistance was detected. The presence of multiple virulence genes was noticed in all isolates. No statistically significant correlation was found between the virulence patterns, bacterial species, and the intensity of clinical symptoms. DISCUSSION: According to the clinical data and the results of this study Aeromonas spp. has an important role in pediatric practice and requires appropriate attention and monitoring.

Spectrum and frequency of CHEK2 variants in breast cancer affected and general population in the Baltic states region, initial results and literature review.

BACKGROUND: While BRCA1/2 gene mutational spectrum and clinical features are widely studied, there is limited data on breast cancer-predisposing non-BRCA pathogenic/likely pathogenic variants (PV/LPVs) in the Baltic states region. According to previous studies, CHEK2 is the most frequent moderate-risk breast cancer predisposition gene. The study aimed to analyse the frequency and mutational spectrum of CHEK2 PV/LPVs in the Baltic states region and perform a literature review on the subject. METHODS: The study includes two cohorts - population-based Estonian biobank (EstBB) (N-152 349) and breast cancer affected cases from Latvia (N-105). In the cohort from Latvia, CHEK2, BRCA1, BRCA2, PALB2 testing with next-generation sequencing (NGS) was carried out in selected breast cancer cases. In the EstBB, the full SNP genotyped dataset Global Screening Array (GSA) (N-152 349) was used to screen CHEK2 PV/LPVs and variants c.319+2T > A (p.(?)), c.444+1G>A (p.(?)), c.433C > T (p.Arg145Trp), c.283C > T (p.Arg95*) in CHEK2 are reported from this dataset. In addition, a subset of the EstBB (N-4776) underwent whole-genome sequencing (WGS, N-2420) and whole-exome sequencing (WES, N-2356) and founder variants c.470T > C (p.Ile157Thr), c.444+1G>A (p.(?)), c.1100delC (p.Thr367Metfs*15) in CHEK2 were reported from this dataset. Moreover, a literature overview was performed on April 1, 2021, using the PubMed search of keywords 'CHEK2', 'breast cancer', 'Estonia', 'Lithuania', 'Latvia', 'Poland', 'Belarus' and 'Russia'. RESULTS: In the breast cancer affected cohort from Latvia 6 CHEK2 variants, classified as PV/LPVs, were observed (6/105; 5.7%), including recurrent ones c.470T > C (p.Ile157Thr) (1.9%) and del5395(ex9-10del; (p.Met304Leufs*16)) (1.9%), as well as single ones - c.1100delC (p.Thr367Metfs*15) (1%) and c.444+1G>A (p.(?)) (1%). From EstBB NGS data (N-4776) CHEK2 variant c.470T > C (p.Ile157Thr) was detected in 8.6% of cases, c.1100delC (p.Thr367Metfs*15) in 0.6% and c.444+1G>A (p.(?)) in 0.2% of cases. In the EstBB full cohort of SNP array data (N-152 349) CHEK2 variant c.444+1G>A (p.(?)) was detected in 0.02% of cases, c.319+2T > A (p.(?)) in 0.09% of cases, c.433C > T (p.Arg145Trp) in 0.02% of cases and c.283C > T (p.Arg95*) in <0.001% of cases. For the literature review altogether, 49 PubMed articles were found, 23 of which were relevant, representing CHEK2 PV/LPVs in the population of interest. Ten publications are from Poland, eight from Russia, three from Latvia and two from Belarus. CONCLUSIONS: This study is the first combined report on complete CHEK2 PV/LPVs screening in selected breast cancer affected cases in Latvia and large-scale population screening in Estonia, providing insight into the CHEK2 mutational spectrum in the Baltic states region. The initial results are in line with other studies that CHEK2 PV/LPVs frequency is around 5-6% of selected breast cancer cases. Here we report three CHEK2 PV/LPV - c.319+2T > A (p.(?)), c.433C > T (p.Arg145Trp), c.283C > T (p.Arg95*), that are novel for the Baltic states region. This is also the first report on c.1100delC (p.Thr367Metfs*15) and c.444+1G>A (p.(?)) from the Baltic states. High population frequency of c.470T > C (p. Ile157Thr) (8.6%) continues to question the variant's pathogenicity in particular populations. Other findings are concordant with previous reports from Latvia and neighbouring populations.

Urinary organic acids spectra in children with altered gut microbiota composition and autistic spectrum disorder.

Introduction: Alteration of human gut microbiota is described in a number of neuro-developmental and cognitive disorders including autistic spectrum disorder (ASD). Along with the changes in the gut microbiota, children with ASD are also reported to have changes in urinary organic acid spectra implying these metabolites as potential biomarkers for gastrointestinal dysbiosis.Aim: Identify urinary metabolites that would indicate specific changes in the gut microbiota and could be useful as biomarkers.Methods: The study group consisted of 44 children with ASD. Urinary organic acids spectra and composition of gut microbiota were analysed.Results: Any significant deviation in quantified metabolites compared to the reference values were not confirmed. The main variations were detected in concentration of p-cresol and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), but we cannot confirm the presence of HPHPA in urine as a biomarker for Clostridium sp. overgrowth in the gut. The acquired results indicate higher relative abundance of Firmicutes phylum alone may be attributed to increased concentration of p-cresol in urine. Decreased Bacteroidetes/Firmicutes ratio was found in the group with the presence of HPHPA in urine.Conclusions: Metabolites of human urine can be used as biomarkers for alterations of gut microbiota with caution, guided treatment should be administrated only based on gut microbiota analysis results or in combination with urinary organic acid results, but not solely based on organic acid biomarkers.

A framework for validating AI in precision medicine: considerations from the European ITFoC consortium.

BACKGROUND: Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. METHODS: The European "ITFoC (Information Technology for the Future Of Cancer)" consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. RESULTS: This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the "ITFoC Challenge". This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. CONCLUSIONS: The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Hypercalcemia and CYP24A1 Gene Mutation Diagnosed in the 2nd Trimester of a Twin Pregnancy: A Case Report.

BACKGROUND Loss-of-function mutations of the CYP24A1 gene cause a deficiency of the CYP24A1 enzyme, which is involved in the catabolism of 1,25-dihydroxyvitamin D3. Patients who are CYP24A1 enzyme deficient are at increased risk of developing hypercalcemia during pregnancy and should avoid additional vitamin D supplementation. This case report provides additional information for managing and diagnosing patients with a CYP24A1 gene mutation. CASE REPORT A primipara woman with a twin pregnancy was admitted to our hospital for frequent hypertensive crises. She had no history of hypercalcemia-associated signs and symptoms except nephrocalcinosis, and reported no other abnormalities or discomfort at presentation. Laboratory tests revealed that the parathyroid hormone level was suppressed and the serum calcium level was markedly increased. The 25-hydroxyvitamin D level was at the upper limit of the reference range while the 1,25-dihydroxyvitamin D3 level was elevated, suggesting a vitamin D catabolism disorder. A genetic test was performed and a homozygous likely pathogenic variant (based on the American College of Medical Genetics and Genomics guidelines) c.964G>A (p.Glu322Lys) was detected in the CYP24A1 gene (NM_000782.5). A cesarean section delivery was performed due to a single intrauterine demise at 33 weeks of gestation. The preterm newborn was diagnosed with transitional hypercalcemia and hyperphosphatemia; however, he was not treated, as he was asymptomatic. CONCLUSIONS Patients with a CYP24A1 gene mutation are at increased risk of hypercalcemia and fetal demise; therefore, 25-hydroxyvitamin D and calcium levels should be monitored in routine blood tests during pregnancy. Hypercalcemia in a newborn should be carefully evaluated and treated, as hypercalciuria can lead to nephrocalcinosis.

Can We Predict Differentiated Thyroid Cancer Behavior? Role of Genetic and Molecular Markers.

Thyroid cancer is ranked in ninth place among all the newly diagnosed cancer cases in 2020. Differentiated thyroid cancer behavior can vary from indolent to extremely aggressive. Currently, predictions of cancer prognosis are mainly based on clinicopathological features, which are direct consequences of cell and tissue microenvironment alterations. These alterations include genetic changes, cell cycle disorders, estrogen receptor expression abnormalities, enhanced epithelial-mesenchymal transition, extracellular matrix degradation, increased hypoxia, and consecutive neovascularization. All these processes are represented by specific genetic and molecular markers, which can further predict thyroid cancer development, progression, and prognosis. In conclusion, evaluation of cancer genetic and molecular patterns, in addition to clinicopathological features, can contribute to the identification of patients with a potentially worse prognosis. It is essential since it plays a crucial role in decision-making regarding initial surgery, postoperative treatment, and follow-up. To date, there is a large diversity in methodologies used in different studies, frequently leading to contradictory results. To evaluate the true significance of predictive markers, more comparable studies should be conducted.

Ultrasound guided needle biopsy of axilla to evaluate nodal metastasis after preoperative systemic therapy in cohort of 106 breast cancers enriched with BRCA1/2 pathogenic variant carriers.

BACKGROUND: Aim of the study is to evaluate the role of ultrasound guided fine needle aspiration cytology (FNAC) in the restaging of node positive breast cancer after preoperative systemic therapy (PST). METHODS: From January 2016 - October 2020 106 node positive stage IIA-IIIC breast cancer cases undergoing PST were included in the study. 18 (17 %) were carriers of pathogenic variant in BRCA1/2. After PST restaging of axilla was performed with ultrasound and FNAC of the marked and/or the most suspicious axillary node. In 72/106 cases axilla conserving surgery and in 34/106 cases axillary lymph node dissection (ALND) was performed. RESULTS: False Positive Rate (FPR) of FNAC after PST in whole cohort and BRCA1/2 positive subgroup is 8 and 0 % and False Negative Rate (FNR) - 43 and 18 % respectively. Overall Sensitivity - 55 %, specificity- 93 %, accuracy 70 %. CONCLUSION: FNAC after PST has low FPR and is useful to predict residual axillary disease and to streamline surgical decision making regarding ALND both in BRCA1/2 positive and negative subgroups. FNR is high in overall cohort and FNAC alone are not able to predict ypCR and omission of further axillary surgery. However, FNAC performance in BRCA1/2 positive subgroup is more promising and further research with larger number of cases is necessary to confirm the results.

Bladder cancer trends in Latvia during 1990-2017: incidence, mortality, and survival rates.

INTRODUCTION: The aim of this article was to evaluate bladder cancer (BC) incidence, mortality and survival trends in Latvia over the past 28 years. MATERIAL AND METHODS: Our study included patients diagnosed with BC between 1990 and 2017. The data were obtained from the national population-based cancer registry. Joinpoint regression analysis was used to identify points where a significant change in incidence and mortality trends occurred, accordingly with the patient's gender and age. Relative survival (RS) was estimated by Ederer I and II methods. RESULTS: Altogether, 9589 patients with initial BC diagnosis were included in the study. The age-standardised (ASR) incidence rates (per 100,000) increased from 6.8 in 1990 to 12.5 in 2014 followed by a statistically insignificant decrease continuing up to 2017. The ASR BC mortality rates (per 100,000) also rose from 3.9 in 1990 to 4.4 in 2017. However, there was a decline in BC mortality trends in the age-group 40-59 with annual percentage change (APC) -1.1%. RS rates increased from 55.0 % in 1990-2000 to 59.0% in years 2013-2017. CONCLUSIONS: This study revealed that the incidence and mortality rates have been gradually increasing over the past 28 years. The exception being cancer-specific mortality in the age group 40-59, which tends to decrease. Although the 5-year RS rates improved over the reviewed period, there is still plenty of room for improvement.

X-Linked Lymphoproliferative Disease in Latvia: A Report of Two Clinically Distinct Cases.

X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency. Affected individuals usually present with the Epstein-Barr virus infection and have no apparent disease prior to presentation. The most common clinical manifestations are fulminant infectious mononucleosis, dysgammaglobulinaemia, and lymphoma (usually of B-cell origin). XLP is caused by mutations in the SH2D1A gene which encodes the intracellular adaptor molecule SAP (signalling lymphocyte activation molecule- (SLAM-) associated protein). SAP is predominantly expressed in T cells and NK cells and functions to regulate signal transduction pathways downstream of the SLAM family of surface receptors to control CD4+ T cell (and by extension B-cell), CD8+ T cell and NK cell function, and development of NKT cells. Thus, SAP mutations cause dysregulation of the immune system, with defects in both cellular and humoral immunity. Here we report two clinical cases of three patients who presented with different manifestations of XLP, namely, fulminant infectious mononucleosis, Burkitt lymphoma and hypogammaglobulinaemia.

The Fetal Phenotype of Noonan Syndrome Caused by Severe, Cancer-Related PTPN11 Variants.

BACKGROUND The nuchal translucency measurement is the major focus of an early fetal ultrasound scan, with the goal to identify various inherited conditions, such as chromosomal aberrations and others. The diagnostic strategy for fetuses with increased nuchal translucency and normal karyotype is not clearly defined and may vary between countries. CASE REPORT We describe 2 cases of Noonan syndrome diagnosed prenatally by ultrasound scanning and genetic testing. The prenatal ultrasound scans showed abnormal nuchal translucencies, cystic lymphangioma/cystic hygroma, and other findings. Both fetuses had normal karyotype; however, after additional analysis, pathogenic variants of the PTPN11 gene (encoding SH2 domain-containing protein tyrosine phosphatase) were found, previously frequently described as somatic variants in hematological malignancies in postnatal life, but not previously described with severe prenatal phenotype of Noonan syndrome. CONCLUSIONS Our case reports confirm the hypothesis that severe, cancer related PTPN11 variants cause severe Noonan syndrome prenatal phenotype, when inherited in the germline.Analysis of pathogenic variants associated with Noonan syndrome should be included in the prenatal diagnostics for fetuses with increased nuchal translucency and normal karyotype.

Pathogenic APC Variants in Latvian Familial Adenomatous Polyposis Patients.

Background and objectives: Familial adenomatous polyposis is one of the APC-associated polyposis conditions described as genetically predetermined colorectal polyposis syndrome with a variety of symptoms. The purpose of this study was to determine sequence variants of the APC gene in patients with familial adenomatous polyposis (FAP) phenotype and positive or negative family history. Materials and Methods: Eight families with defined criteria of adenomatous polyposis underwent molecular genetic testing. Coding regions and flanking intron regions of the APC gene were analyzed by Sanger sequencing. Results: Eight allelic variants of the APC gene coding sequence were detected. All allelic variants of the APC gene were predicted to be pathogenic based on criteria according to the "Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology" (2015), four of them c.1586_1587insAT, c.2336delT, c.3066_3067insGA, and c.4303_4304insC, were considered novel. Conclusions: The timely molecular genetic analysis of APC germline variants and standardized interpretation of the pathogenicity of novel allelic variants has a high impact on choice for treatment, cancer prevention, and family genetic counseling.

Allelic variants of breast cancer susceptibility genes PALB2 and RECQL in the Latvian population.

BACKGROUND: Large-scale case control studies revealed a number of moderate risk - low frequency breast cancer alleles of the PALB2 and RECQL genes. Some of these were reported as founder variants of Central and Eastern Europe. Based on highly similar founder variant spectra of the BRCA1 in Poland and Latvia, we decided to test the frequency of other common variants of moderate breast cancer risk - c.509_510delGA (rs515726124) and c.172_175delTTGT (rs180177143) of the PALB2 gene and c.1667_1667+3delAGTA variant of the RECQL gene in a breast cancer case-control series from Latvia to better understand the role of genes in susceptibility to breast cancer and their clinical significance. METHODS: The case-control study was performed based on an unselected breast cancer case group of 2480 women and a control group, including 1240 voluntary, to our knowledge unrelated, female donors without reported oncological disease. RESULTS: The calculated frequency for c.509_510delGA of the PALB2 gene in the case group is 0.35 and 0.00% in the control group, with respective relative risk (RR) 7.18 (CI 95% 0.37-138.75; p = 0.19). As for the PALB2 c.172_175delTTGT variant, the frequency in the case group of our study is 0.04%. In the control group of our study all individuals were homozygous for the wild-type allele, which lead to calculated RR = 1.50 (CI 95% 0.06-36.83; p-value = 0.80). There were no carriers of the RECQL variant c.1667_1667+3delAGTA identified in our case group and 2 heterozygotes were identified in the control group. The calculated RR = 0.26 (CI 95% 0.01-5.33; p-value = 0.38). CONCLUSION: Results obtained for the PALB2 gene variants are able to supplement evidence on the allele frequency in breast cancer patients from the region of Central and Eastern Europe. Based on our results we cannot confirm the contribution of the RECQL variant c.1667_1667+3delAGTA allele to breast cancer development.

An Effect of Culture Media on Epithelial Differentiation Markers in Breast Cancer Cell Lines MCF7, MDA-MB-436 and SkBr3.

Background and objectives: Cell culture is one of the mainstays in the research of breast cancer biology, although the extent to which this approach allows to preserve the original characteristics of originating tumor and implications of cell culture findings to real life situations have been widely debated in the literature. The aim of this study was to determine the role of three cell culture media on transcriptional expression of breast cancer markers in three breast cancer reference cell lines (MCF7, SkBr3 and MDA-MB-436). Materials and methods: Cell lines were conditioned in three studied media (all containing 5% fetal bovine serum (FBS) + hormones/growth factors; different composition of basal media) for four passages. Population growth was characterized by cumulative population doubling levels, average generation time, cell yield and viability at the fourth passage. Transcriptional expression of breast cancer differentiation markers and regulatory transcriptional programs was measured by qPCR. Results: Differences in the composition of growth media significantly influenced the growth of studied cell lines and the expression of mammary lineage governing transcriptional programs and luminal/basal markers. Effects of media on transcriptional expression were more pronounced in luminal cell lines (MCF7, SkBr3), than in the basal cell line (MDA-MB-436). Changes in growth media in terms of supplementation and basal medium delayed growth of cells, but improved cell yields. Conclusions: The expression of breast cancer cell differentiation phenotypic markers depends on the composition of cell growth medium, therefore cell culture as a tool in phenotypic studies should be used considering this effect. The findings of such studies should always be interpreted with caution. The formulation of cell growth media has greater effect on the expression of phenotypic markers in luminal, rather than basal cell lines. Media containing mitogens and higher vitamin content improved efficacy of cell culture in terms of cell yields, although greatly increased growth times.

Platinum-based neoadjuvant chemotherapy in BRCA1-positive breast cancer: a retrospective cohort analysis and literature review.

BACKGROUND: There is increasing evidence of high platinum sensitivity in BRCA-associated breast cancer. However, evidence from randomized trials is lacking. The aim of this study was to analyze the results of platinum-based chemotherapy for BRCA1-positive breast cancer in a neoadjuvant setting. METHODS: A retrospective study was performed by obtaining information from patient files. The results were compared with the available data from a literature review. RESULTS: Twelve female patients with BRCA1 gene mutations who had stage I to III breast cancers were eligible for evaluation. They received platinum-based neoadjuvant chemotherapy between 2011 and 2016. Eleven patients received a combination of cisplatin and doxorubicin, and one patient received carboplatin and docetaxel. All patients underwent mastectomy after chemotherapy. Ten patients (83%) achieved pathological complete remission (pCR). The observed pCR rate was comparable to existing results found in similar studies. CONCLUSION: The results of the study confirm the high pCR rate in BRCA1-positive breast cancer after platinum-based neoadjuvant chemotherapy. Larger randomized studies and longer follow-up times are necessary to evaluate the role of platinum-based therapies in BRCA1-positive breast cancer.

Chromothripsis and progression-free survival in metastatic colorectal cancer.

Metastatic dissemination of the primary tumor is the major cause of death in colorectal cancer (CRC) patients. Multiple chromosomal breaks and chromothripsis, a phenomenon involving multiple chromosomal fragmentations occurring in a single catastrophic event, are associated with cancer genesis, progression and developing of metastases. The aim of this study was to evaluate the effect of chromothripsis and total breakpoint count (breakpoint instability index) on progression-free survival (PFS). A total of 19 patients with metastatic CRC (mCRC) receiving FOLFOX first-line palliative chemotherapy between August, 2011 and October, 2012 were selected for this study. The results indicated that the highest breakpoint count was observed in chromosomes 1, 2 and 6. Chromothripsis was detected in 52.6% of the study patients. Furthermore, chromothripsis was associated with an increased median PFS (mPFS; 14 vs. 8 months, respectively; P=0.03), but an association with overall survival was not identified. The present study demonstrated that chromothripsis affected CRC patient survival, suggesting a role for this event as a prognostic and predictive marker in mCRC treatment.

Presence of Methicillin-resistant Staphylococcus Aureus in Slaughterhouse Environment, Pigs, Carcasses, and Workers.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a highly resistant and difficult to cure zoonotic microorganism, which makes up a large part of food toxic infections and has shown high prevalence among pig population all over the world. The aim of the study was to establish the occurrence of MRSA in slaughterhouses, evaluate its antimicrobial resistance, and verify whether there are any differences or similarities with reference to other European countries. MATERIAL AND METHODS: A total of 100 pigs, 105 carcasses, 19 workers, and 24 samples from the environment of several slaughterhouses were examined by conventional microbial and molecular methods. RESULTS: In total, 78 MRSA isolates were found. MRSA prevalence in slaughtered pigs varied from 8.0% to 88.6% depending on the slaughterhouse, reaching higher prevalence in slaughterhouses with higher slaughter capacity. In total, 21.1% of all workers were carriers of MRSA and 6.7% of carcasses were contaminated with MRSA. The 98.2% of MRSA isolates were resistant to penicillin, 89.1% to tetracycline, 60.1% to erythromycin, 65.5% to gentamycin, and 15 different spa types were found, among which spa type t01333 was most widespread. CONCLUSION: The study indicated that MRSA prevalence and spa types differed according to slaughterhouse slaughter capacity and good hygiene practices. Quite high MRSA occurrence among slaughterhouse workers is one of the main factors which increase pork contamination risk.

MRSA in Pig Population.

Methicillin resistant Staphylococcus aureus (MRSA) is widespread worldwide in different types of animal species and as a zoonosis takes a great risk for human health not only as a food toxicoinfection, but also as a highly resistant pathogen causing serious soft tissue infectious, septicaemia and even death. One of the most affected food-producing animal species is swine in the production of which new antibiotics in big amounts are used more and more continuously, increasing antimicrobial resistance. In this study several commercial pig farms and pigs with different age groups as well as farm workers and samples from environment were examined with the purpose of detecting MRSA prevalence and evaluating antimicrobial resistance. A total of 85 isolated MRSA strains were characterised by conventional microbial and molecular methods. MRSA was found in all farms. MRSA prevalence in different pig age groups and farms varied from none to 79.2% reaching higher values among 3-3.5 (26.6%) and 4-4.5 (31.9%) old pigs. The 98.7% of 74 further investigated MRSA isolates were resistant to penicillin, 94.9% to tetracycline, 45.6% to cephalexin and 10 different spa types were found among which spa type t011 was the most widespread. To the best of our knowledge, this is the first time MRSA was researched in sow milk and the first description of the presence of MRSA in several age groups of pigs in Latvia.