Machine Learning and Clinical Predictors of Mortality in Cardiac Arrest Patients: A Comprehensive Analysis.

BACKGROUND Cardiac arrest (CA) is a global public health challenge. This study explored the predictors of mortality and their interactions utilizing machine learning algorithms and their related mortality odds among patients following CA. MATERIAL AND METHODS The study retrospectively investigated 161 medical records of CA patients admitted to the Intensive Care Unit (ICU). The random forest classifier algorithm was used to assess the parameters of mortality. The best classification trees were chosen from a set of 100 trees proposed by the algorithm. Conditional mortality odds were investigated with the use of logistic regression models featuring interactions between variables. RESULTS In the logistic regression model, male sex was associated with 5.68-fold higher mortality odds. The mortality odds among the asystole/pulseless electrical activity (PEA) patients were modulated by body mass index (BMI) and among ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) patients were by serum albumin concentration (decrease by 2.85-fold with 1 g/dl increase). Procalcitonin (PCT) concentration, age, high-sensitivity C-reactive protein (hsCRP), albumin, and potassium were the most influential parameters for mortality prediction with the use of the random forest classifier. Nutritional status-associated parameters (serum albumin concentration, BMI, and Nutritional Risk Score 2002 [NRS-2002]) may be useful in predicting mortality in patients with CA, especially in patients with PCT >0.17 ng/ml, as showed by the decision tree chosen from the random forest classifier based on goodness of fit (AUC score). CONCLUSIONS Mortality in patients following CA is modulated by many co-existing factors. The conclusions refer to sets of conditions rather than universal truths. For individual factors, the 5 most important classifiers of mortality (in descending order of importance) were PCT, age, hsCRP, albumin, and potassium.

Perioperative anaesthetic management and short-term outcome of neonatal repair of oesophageal atresia with or without tracheo-oesophageal fistula in Europe: A sub-analysis of the neonate and children audit of anaesthesia practice in Europe (NECTARINE) prospective multicenter observational study.

BACKGROUND: Oesophageal atresia with or without a tracheo-oesophageal fistula is a congenital abnormality that usually requires surgical repair within the first days of life. OBJECTIVE: Description of the perioperative anaesthetic management and outcomes of neonates undergoing surgery for oesophageal atresia with or without a tracheo-oesophageal fistula, included in the 'neonate and children audit of anaesthesia practice in Europe' (NECTARINE) database. DESIGN: Sub-analyses of prospective observational NECTARINE study. SETTING: European multicentre study. PATIENTS: Neonates who underwent surgery for oesophageal atresia with or without a tracheo-oesophageal fistula in the NECTARINE cohort were selected. MAIN OUTCOME MEASURES: Incidence rates with 95% confidence intervals were calculated for peri-operative clinical events which required a predetermined intervention, postoperative complications, and mortality. RESULTS: One hundred and three neonates undergoing a first surgical intervention for oesophageal atresia with or without a tracheo-oesophageal fistula repair were identified. Their median gestational age was 38 weeks with a median birth weight of 2840 [interquartile range 2150 to 3150] grams. Invasive monitoring was used in 66% of the procedures. The incidence of perioperative clinical events was 69% (95% confidence interval 59 to 77%), of 30-day postoperative complications 47% (95% confidence interval 38 to 57%) and the 30- and 90 days mortality rates were 2.1% and 2.6%, respectively. CONCLUSION: Oesophageal atresia with or without a tracheo-oesophageal fistula repair in neonates is associated with a high number of perioperative interventions in response to clinical events, a high incidence of postoperative complications, and a substantial mortality rate.

Platelet dysfunction in a large-animal model of endotoxic shock; effects of inhaled nitric oxide and low-dose steroid.

OBJECTIVE: The role of inhaled nitric oxide in the treatment of shock remains controversial and further translational research is needed. Long-term observation studies using a model of endotoxin-induced shock to assess the effect of inhaled nitric oxide on platelet aggregation have not yet been reported. APPROACH AND RESULTS: The tests were carried out in an animal model of shock in two 10-h periods. During the first 10 h, endotoxin was infused and the inhibition of platelet aggregation was evaluated; following the termination of endotoxin infusion, the restoration of platelet aggregation was assessed for 10 h. A total of 30 pigs were used (NO group, N = 14; control, N = 16). In the NO group, nitric oxide inhalation (30 ppm) was started 3 h after endotoxin infusion and continued until the end of the study. Treatment with NO selectively decreased pulmonary artery pressure at 4 (p = 0.002) and 8 h (p = 0.05) of the experiment as compared to the control. Endotoxin significantly reduced platelet aggregation, as indicated by the decreased activity of platelet receptors: ASPI, ADP, collagen, and TRAP during the experiment (p < 0.001). Endotoxin had no significant effect on changes in the response of the receptor after ristocetin stimulation. After stopping endotoxin infusion, a significant restoration of receptor activity was observed for collagen and TRAP, while ASPI and ADP remained partially depressed. Inhaled nitric oxide did not cause additional inhibition of platelet aggregation, either during or after endotoxin challenge. CONCLUSIONS: A profound reduction in platelet aggregation was observed during endotoxic shock. After stopping endotoxin infusion a restoration of platelet receptor activity was seen. The inhibition of platelet aggregation induced by endotoxin infusion was not intensified by nitric oxide, indicating there was no harmful effect of inhaled nitric oxide on platelet aggregation.

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE).

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants. CLINICAL TRIAL REGISTRATION: NCT02350348.

Vitamin D, Vitamin D Receptor (VDR) Gene Polymorphisms (ApaI and FokI), and Bone Mineral Density in Patients With Inflammatory Bowel Disease.

In the etiology of inflammatory bowel disease (IBD) and osteoporosis, the connecting element is the involvement of environmental and genetic factors. Vitamin D receptor (VDR) gene polymorphisms may be associated with the pathogenesis of IBD and bone mineral density (BMD). The study aimed to analyze the relationship between ApaI and FokI polymorphisms of the VDR gene, serum vitamin D concentration, and BMD in patients with IBD. The studied group consisted of 172 patients (85 with Crohn's disease [CD], 87 with ulcerative colitis [UC], and 39 healthy subjects - control group [CG]) were examined. Lumbar spine densitometry (L1-L4) and the femoral neck (FN) measurements were performed using dual-energy X-ray absorptiometry (DXA). Serum concentrations of 25-hydroxyvitamin D were determined using electrochemiluminescence binding assay (ECLIA). Polymorphisms were determined with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). . We found no statistically significant differences in vitamin D concentration between the 3 studied groups. CD patients who were FF homozygotes had significantly lower FN BMD than FF homozygous from CG (p-value < 0.05). CD patients who were Aa heterozygotes had significantly lower lumbar spine (L2-L4) BMD than Aa heterozygotes from CG (p-value < 0.05). Among patients with the same polymorphic variants, but belonging to different studied groups, statistically significant differences in bone mineral density in the lumbar spine and the closer end of the femoral neck were observed. We consider that it is the disease entity, not the polymorphism variant, may have a decisive impact on BMD.

Factors affecting survival in children requiring intensive care after hematopoietic stem cell transplantation. A retrospective single-center study.

Allo-HSCT is associated with life-threatening complications. Therefore, a considerable number of patients require admission to a PICU. We evaluated the incidence and outcome of PICU admissions after allo-HSCT in children, along with the potential factors influencing PICU survival. A retrospective chart review of 668 children who underwent first allo-HSCT in the Department of Pediatric Hematology/Oncology and BMT in Wroclaw during years 2005-2017, particularly focusing on patients admitted to the PICU within 1-year post-HSCT. Fifty-eight (8.7%) patients required 64 admissions to the PICU. Twenty-four (41.5%) were discharged, and 34 (58.6%) patients died. Among the discharged patients, 6-month survival was 66.7%. Compared with survivors, death cases were more likely to have required MV (31/34; 91.2% vs. 16/24; 66.7% P = .049), received more aggressive cardiac support (17/34; 50% vs. 2/24; 8.3% P = .002), and had a lower ANC on the last day of their PICU stay (P = .004). Five patients were successfully treated with NIV and survived longer than 6 months post-discharge. The intensity of cardiac support and ANC on the last day of PICU treatment was independent factors influencing PICU survival. Children admitted to the PICU after allo-HSCT have a high mortality rate. Mainly those who needed a more aggressive approach and had a lower ANC on the last day of treatment had a greater risk of death. While requiring MV is associated with decreased PICU survival, early implementation of NIV might be considered.

Factors associated with return of spontaneous circulation after out-of-hospital cardiac arrest in Poland: a one-year retrospective study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a common reason for calls for intervention by emergency medical teams (EMTs) in Poland. Regardless of the mechanism, OHCA is a state in which the chance of survival is dependent on rapid action from bystanders and responding health professionals in emergency medical services (EMS). We aimed to identify factors associated with return of spontaneous circulation (ROSC). METHODS: The medical records of 2137 EMS responses to OHCA in the city of Wroclaw, Poland between July 2017 and June 2018 were analyzed. RESULTS: The OHCA incidence rate for the year studied was 102 cases per 100,000 inhabitants. EMS were called to 2317 OHCA events of which 1167 (50.4%) did not have resuscitation attempted on EMS arrival. The difference between the number of successful and failed cardiopulmonary resuscitations (CPRs) was statistically significant (p < 0.001). Of 1150 patients in whom resuscitation was attempted, ROSC was achieved in 250 (27.8%). Rate of ROSC was significantly higher when CPR was initiated by bystanders (p < 0.001). Patients presenting with asystole or pulseless electrical activity (PEA) had a higher risk of CPR failure (86%) than those with ventricular fibrillation/ventricular tachycardia (VF/VT). Patients with VF/VT had a higher chance of ROSC (OR 2.68, 1.86-3.85) than those with asystole (p < 0.001). The chance of ROSC was 1.78 times higher when the event occurred in a public place (p < 0.001). CONCLUSIONS: The factors associated with ROSC were occurrence in a public place, CPR initiation by witnesses, and presence of a shockable rhythm. Gender, age, and the type of EMT did not influence ROSC. Low bystander CPR rates reinforce the need for further efforts to train the public in CPR.

Is the Retinol-Binding Protein 4 a Possible Risk Factor for Cardiovascular Diseases in Obesity?

Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group. In our review, we summarized the current knowledge about RBP4 and its association with essential aspects of cardiovascular disease-lipid profile, intima-media thickness, atherosclerotic process, and diet. We also discussed the RBP4 gene polymorphisms essential from a cardiovascular perspective.

Long-range PCR libraries and next-generation sequencing for pharmacogenetic studies of patients treated with anti-TNF drugs.

Biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies significantly increased the effectiveness of autoimmune disease treatment compared with conventional medicines. However, anti-TNF-α drugs are relatively expensive and a response to the therapy is reported in only 60-70% of patients. Moreover, in up to 5% of patients adverse drug reactions occur. The various effects of biological treatment may be a potential consequence of interindividual genetic variability. Only a few studies have been conducted in this field and which refer to single gene loci. Our aim was to design and optimize a methodology for a broader application of pharmacogenetic studies in patients undergoing anti-TNF-α treatment. Based on the current knowledge, we selected 16 candidate genes: TNFRSF1A, TNFRSF1B, ADAM17, CASP9, FCGR3A, LTA, TNF, FAS, IL1B, IL17A, IL6, MMP1, MMP3, S100A8, S100A9, and S100A12, which are potentially involved in the response to anti-TNF-α therapy. As a research model, three DNA samples from Crohn's disease (CD) patients were used. Targeted genomic regions were amplified in 23 long-range (LR) PCR reactions and after enzymatic fragmentation amplicon libraries were prepared and analyzed by next-generation sequencing (NGS). Our results indicated 592 sequence variations located in all fragments with coverage range of 5-1089. We demonstrate a highly sensitive, flexible, rapid, and economical approach to the pharmacogenetic investigation of anti-TNF-α therapy using amplicon libraries and NGS technology.

Safe pediatric procedural sedation and analgesia by anesthesiologists for elective procedures: A clinical practice statement from the European Society for Paediatric Anaesthesiology.

The growing number of medical procedures performed in children that require cooperation of patients, lack of movement, anxiolysis or/and analgesia triggers the increased need for procedural sedation. This document presents the consensus statement of the European Society for Paediatric Anaesthesiology about the principles connected with the safe management of procedural sedation and analgesia (PSA) by anaesthesiologists for elective procedures in children. It does not aim to provide a legal statement on how and by whom PSA should be performed. The document highlights that any staff taking part in sedation of children must be appropriately trained with the required competencies and must be able to demonstrate regularly that they have maintained their knowledge, skills and clinical experience. The main goal of creating this document was to reflect the opinions of the community of the paediatric anaesthesiologists in Europe regarding how PSA for paediatric patients should be organized to make it safe.

Bitter taste of Brassica vegetables: The role of genetic factors, receptors, isothiocyanates, glucosinolates, and flavor context.

It is well known that consumption of Brassica vegetables has beneficial effect on human's health. The greatest interest is focused on glucosinolates and their hydrolysis products isothiocyanates, due to their potential as cancer preventing compounds. Brassica vegetables are also rich in flavor compounds belonging to many chemical groups. The main sensory sensation related to these vegetable is their characteristic sharp and bitter taste, and unique aroma. Because of these features this group of vegetables is often rejected by consumers. Interestingly, for some people unpleasant sensations are not perceived, suggesting a potential role of inter-individual variability in bitter taste perception and sensibility. Receptors responsible for bitter sensation with the emphasis on Brassica are reviewed, as well as genetic predisposition for bitterness perception by consumers. Also the role of glucosinolates and isothiocyanates as compounds responsible for bitter taste is discussed based on data from the field of food science and molecular biology. Isothiocyanates are shown in broaded context of flavor compounds also contributing to the aroma of Brassica vegetables.

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative).

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice.

Genetic polymorphism in psoriasis and its meaning for the treatment efficacy in the future.

The concept of personalized medicine is a new individualized approach which helps application of the targeted therapy. In fact, tailored medicine is mostly present in the field of life-threatening diseases such as oncology. However, skin diseases as such might be regarded as a potential area of implementation of this approach in the future. Stratified medicine in polygenetic and heterogeneous diseases, such as psoriasis, is more complex. Rapid development of science and novel molecular techniques led to better understanding of molecular pathogenetic pathways of many diseases including psoriasis. Identification of the particular immunopathogenetic pathways led to further development of targeted therapies such as biologic drugs. Actually the goal of individualized therapy is to determine the identical homogenous subgroups of patients, according to a biomarker, in which the response to that therapy will be the best and will carry the lowest risk of side effects. This review attempts to analyze the associations between polymorphisms of certain genes and the increased risk of developing psoriasis or psoriatic arthritis. The review of literature has also included the studies investigating the associations between gene polymorphisms and response to biologic therapy in psoriasis and psoriatic arthritis patients.

Effects of Intrauterine Environment on the Magnitude of Differences Within the Pairs of Monozygotic and Dizygotic Twins.

The aim of this study was to determine the effects of intrauterine environment on the magnitude of intrapair differences in six somatic traits of monozygotic (MZ) and dizygotic (DZ) twins (1,263 pairs; 424 MZ twins and 839 DZ twins). Differences in intrauterine environments of MZ twins enforced division of the research material into four groups: (1) MZ-MC-TTTS - MZ twins from monochorionic (MC) pregnancies with twin-to-twin transfusion syndrome (TTTS), (2) MZ-MC (without TTTS)-MZ twins from MC pregnancies without TTTS, (3) MZ-DC-MZ twins from dichorionic (DC) pregnancies, and (4) DZ-DZ twins. The intrapair differences in all analyzed somatic traits, especially body weight and circumference of the chest, were the largest in the case of MZ twins from MC pregnancies with TTTS. DZ twins were the group presenting with the second largest intrapair differences in the analyzed traits. At the end of pregnancy, that is, in lunar months 9 and 10, the magnitude of intrapair differences in all traits of twins from this group was significantly greater than in MZ twins from both MC and DC pregnancies. Irrespective of the analyzed period, the least evident, statistically insignificant intrapair differences in the studied traits were documented in the case of MZ twins from MC pregnancies without TTTS and twins from DC pregnancies. These findings imply that the differentiating effect of intrauterine environment is associated with the occurrence of TTTS, rather than with chorionicity, as postulated previously.

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia.

BACKGROUND: The serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane. METHODS: The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated. RESULTS: The allele GSTA1*B (-567G, -69T, -52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia. CONCLUSIONS: GSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

Bone Metabolism and the c.-223C > T Polymorphism in the 5'UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease.

Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn's disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases.

The impact of genetic factors on response to glucocorticoids therapy in IBD.

Glucocorticosteroids (GCs) are used for many years as first-line drugs for the achievement of remission in exacerbations of inflammatory bowel disease (IBD). However, close to 20% of patients are resistant to GCs, and 40% of patients become dependent on GCs. The challenge of today's personalized medicine is the anticipation of the steroid therapy effects even before the initiation of treatment. As several studies show, individually variable response to GCs in population has a genetic background and may depend on gene variability encoding proteins involved in the function and metabolism of GCs. To those genes belong: NR3C1--responsible for the synthesis of GC receptor (GR); Hsp90, HSP70, STIP1, FKB5--genes of GR protein complex; ABCB1 and IPO13 coding glycoprotein p170; and importin 13--involved in GCs transport; IL1A, IL1B, IL2, IL4, IL8, IL10, TNF, and MIF--genes of the epithelial pro-inflammatory factors synthesis, which excessive activation causes steroid resistance as well as CYP3A4 and CYP3A5--encoding GCs biotransformation enzymes. This work systematizes and sums up the state of current knowledge in the field of pharmacogenetics as well as expectations for the future in the realm of individualized medicine in IBD patients treated with GC drugs.

The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population.

BACKGROUND: Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible. The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene. AIM OF THE STUDY: The aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer. METHODS: 602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher's exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software. RESULTS: The results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019). CONCLUSIONS: Identification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered.

Successful production of piglets derived from mature oocytes vitrified using OPS method.

OBJECTIVE: Examination of effect of vitrification solution with or without foetal calf serum (FCS) on the in vitro and in vivo survival of matured pig oocytes. MATERIALS AND METHODS: Exp. 1: oocytes were exposed to vitrification solutions: VSa (15% DMSO, 15% EG, 0.5 M sucrose dissolved in TCM-199 with FCS) or VSb (VSa without FCS). Exp. 2: oocytes were vitrified in VSa or VSb using OPS. A fraction of vitrified oocytes were transferred to 6 synchronised and inseminated recipients.. RESULTS: Survival rate after exposure and vitrification was the same for VSa and VSb. Transfer of 48 oocytes vitrified in VSb resulted with two pregnancies and 12 live piglets. Molecular analysis results: eight piglets originated from the surrogate mother's oocytes, four piglets from vitrified oocytes.. CONCLUSION: The use of DMSO and EG as cryoprotectants without serum supplementation was advantageous for the in vivo development of vitrified mature porcine oocytes.