ABCA3 and LZTFL1 Polymorphisms and Risk of COVID-19 in the Czech Population.

SARS-CoV-2 infection, which causes the respiratory disease COVID-19, has spread rapidly from Wuhan, China, since 2019, causing nearly 7 million deaths worldwide in three years. In addition to clinical risk factors such as diabetes, hypertension, and obesity, genetic variability is an important predictor of disease severity and susceptibility. We analyzed common polymorphisms within the LZTFL1 (rs11385942) and ABCA3 (rs13332514) genes in 519 SARS-CoV-2-positive subjects (164 asymptomatic, 246 symptomatic, and 109 hospitalized COVID-19 survivors) and a population-based control group (N?=?2,592; COVID-19 status unknown). Rare ABCA3 AA homozygotes (but not A allele carriers) may be at a significantly increased risk of SARS-CoV-2 infection [P?=?0.003; OR (95 % CI); 3.66 (1.47-9.15)]. We also observed a borderline significant difference in the genotype distribution of the LZTFL1 rs11385942 polymorphism (P?=?0.04) between the population sample and SARS-CoV-2-positive subjects. In agreement with previous studies, a nonsignificantly higher frequency of minor allele carriers was detected among hospitalized COVID-19 subjects. We conclude that a common polymorphism in the ABCA3 gene may be a significant predictor of susceptibility to SARS-CoV-2 infection.

A haemochromatosis-causing HFE mutation is associated with SARS-CoV-2 susceptibility in the Czech population.

BACKGROUND: Coronavirus disease (COVID-19), which is caused by the SARS-CoV-2 virus, has become a global pandemic. While susceptibility to COVID-19 is subject to several external factors, including hypertension, BMI, and the presence of diabetes, it is also genetically determined to a significant extent. Infectious agents require iron (Fe) for proper functioning. Carriers of mutations resulting in increased iron concentrations are understood to be at increased risk of COVID-19. METHODS: We examined HFE genotypes associated with hereditary haemochromatosis (rs1800562 and rs1799945 SNPs) in 617 COVID-19 patients (166 asymptomatic, 246 symptomatic and 205 hospitalised survivors) and 2 559 population-based controls. RESULTS: We found a higher frequency of the minor allele (Tyr282) of the rs1800562 polymorphism (P < 0.002) in patients compared to controls (8.5 % vs 5.5 %). Non-carriers of the minor allele were protected against SARS-Cov-2 infection (OR, 95 %CI; 0.59, 0.42-0.82). The frequency of minor allele carriers was almost identical across asymptomatic, symptomatic, and hospitalised survivors. The rs1799945 variant did not affect disease severity and its occurrence was almost identical in patients and controls (P between 0.58 and 0.84). CONCLUSIONS: In conclusion, our results indicate that presence of the rs1800562 minor allele, which is associated with hereditary haemochromatosis (thus increased levels of plasma Fe), increases susceptibility to SARS-CoV-2.

Diagnosis and treatment of surgical skin and soft tissue infections - current status.

Surgical skin and soft tissue infections (SSTIs) result from microbial invasion of the skin and underlying soft tissues, often requiring surgical treatment. SSTIs encompass a variety of pathological conditions, ranging from frequent simple superficial skin infections with very good outcomes to rare, rapidly progressive necrotizing infections associated with long-lasting morbidity and high mortality. The document summarizes current knowledge of the diagnosis and therapy of these diseases and provides clinicians with current standards of care of these patients based on international guidelines. Additionally, regional specific aspects are also reflected, and thus in all cases, this paper on diagnostic-therapeutic management of individual clinical forms respects the actual clinical practice and epidemiology in the Czech Republic. The document has been prepared based on multidisciplinary consensus of experts from universities all over the Czech Republic.

Microbiological analysis of peritoneal fluid samples from patients with perforated peptic ulcer - retrospective observational study.

INTRODUCTION: Peritonitis due to perforated peptic ulcer (PPU) is a surgical emergency associated with high mortality. Preoperative management includes immediate initiation of broad-spectrum antimicrobial therapy. The objective of this study was to assess the spectrum of microbial pathogens in peritoneal fluid. METHODS: Retrospective observational study of patients who underwent surgery for PPU at the 1st Department of Surgery - Thoracic, Abdominal and Injury Surgery, General University Hospital in the period 2015-2020. Analysis of the microbiological analytical results of peritoneal fluid. RESULTS: The microbiological profile of PPU-associated peritonitis is somewhat different from microbial pathogens involved in secondary peritonitis due to bowel perforation. A high rate of negative culture findings, high incidence of Candida spp. and low incidence of anaerobic bacteria are characteristic for PPU-associated peritonitis. Negative culture from the peritoneal fluid collected during surgery was identified in 42% of the patients. A total of 66 isolates of microbial pathogens were identified, including Candida spp. (42.5%), aerobic gram-positive bacteria (30.3%), aerobic gram-negative bacteria (22.7%) and anaerobic bacteria (4.5%). Candida albicans and Candida glabrata represented the most common species. Decreased susceptibility to fluconazole and resistance to itraconazole was associated with all Candida glabrata isolates. CONCLUSION: Although PPU-associated peritonitis is mostly of community origin, we confirmed a significant incidence of Candida spp. with decreased azole susceptibility. The choice of antifungal therapy should always be based on local epidemiology.

Antimicrobial activity of ceftazidime-avibactam and comparators against Pseudomonas aeruginosa and Enterobacterales collected in Croatia, Czech Republic, Hungary, Poland, Latvia and Lithuania: ATLAS Surveillance Program, 2019.

Antimicrobial susceptibility of clinical isolates collected from sites in central Europe in 2019 was tested by CLSI broth microdilution method and EUCAST breakpoints. Most active were amikacin, ceftazidime-avibactam and colistin; respectively, susceptibility rates among P. aeruginosa (n = 701) were 89.2%, 92.2% and 99.9%; difficult-to-treat (DTR) isolates, 62.5%, 37.5% and 100%; multidrug-resistant (MDR) isolates, 68.3%, 72.9% and 99.5%; meropenem-resistant (MEM-R), metallo-ß-lactamase-negative (MBL-negative) isolates, 72.8%, 78.6% and 100%. Among Enterobacterales (n = 1639), susceptibility to ceftazidime-avibactam, colistin and tigecycline was ≥ 97.9%; MDR Enterobacterales, 96.8%, 94.4% and 100%, respectively; DTR isolates, ≥ 76.2% to ceftazidime-avibactam and colistin; MEM-R, MBL-negative isolates, ≥ 90.0% to ceftazidime-avibactam and colistin.

CCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Delta32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5?32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Delta32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5?32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.

Can gram-negative-like biomarker values in Streptococcus pyogenes sepsis negatively influence right choice of initial antibiotic therapy?

Úvod: Biomarkery jsou u septických pacientů využívány jak k diagnostice sepse, tak k antibiotickému stewardshipu. Sepse vyvolaná gramnegativními bakteriemi mívá odlišné charakteristiky, především vysoký prokalcitonin vs C-reaktivní protein v porovnání se sepsí vyvolanou grampozitivními bakteriemi. Avšak jednotlivá infekční agens, především Streptococcus pyogenes, nemusí do tohoto schématu zapadat, což může vest k nesprávné iniciální volbě antibiotika. Metody: Retrospektivní analýza biomarkerů, iniciální volby antibiotické léčby a výsledků léčby u pacientů se sepsí vyvolanou S. pyogenes, Escherichia coli a Staphylococcus aureus. Hodnoty biomarkerů byly porovnány pomocí Kruskal-Wallis testu s následným Dunn post-Hoc testem s prahem p < 0,05. Výsledky: Hodnoty prokalcitoninu byly nejvyšší u sepse vyvolané S. pyogenes (12,51 ng/ml, IQR: 6,26-48,38 ng/ml) oproti sepsi vyvolaná E. coli (4,30 ng/ml, IQR: 1,50-10,00 ng/ml, p < 0,001) a S. aureus (0,75 ng/ml, QR: 0,34-1,62 ng/ml, p < 0,001). Poměr neutrofilů a lymfocytů vykazoval stejné charakteristiky jako prokalcitonin. Správná iniciální antibiotická léčba byla v souboru S. pyogenes 11,29 % v porovnání s 99,3 % a 100 % u S. aureus a E. coli skupin. Závěr: Oproti předchozím studiím byly v našem souboru pozorovány nejvyšší hodnoty prokalcitoninu u pacientů se sepsí vyvolanou S. pyogenes spíše než gramnegativními bakteriemi. Vysoké hodnoty prokalcitoninu imitující gramnegativní zánětlivou odpověď přispěli k ovlivnění výběru iniciální antibiotické léčby (bez znalosti původce), což mohlo vést k vyšší mortalitě u této skupiny pacientů. Proto doporučujeme přehodnocení významu prokalcitoninu v diagnostice sepse pro zlepšení přežití i kvality života pacientů.

Intra-abdominal candidiasis in surgical intensive care unit - epidemiology characteristics and trends.

OBJECTIVES: Intra-abdominal candidiasis (IAC) is an invasive fungal infection representing the most common type of invasive Candida infection in surgical intensive care units (ICUs). Recently, decreased antifungal susceptibility and progressive shift in the aetiology of invasive candidiasis has been observed worldwide. We explored IAC epidemiology in surgical ICU. MATERIAL AND METHODS: We retrospectively reviewed the records of 64 patients with IAC admitted at our surgical ICU over a 4-year period (2013-2016). IAC incidence, microbiological results, antifungal therapy, and mortality were analysed. RESULTS: The cumulative IAC incidence was 18.4 cases per 1000 admissions (2013: 12.6; 2014: 17.7; 2015: 16.8; 2016: 24.5), including hospital-acquired IAC incidence (2013: 9.8; 2014: 13.3; 2015 10.1; 2016: 13.3) and community-acquired IAC incidence (2013: 2.8; 2014: 4.4; 2015: 6.7; 2016: 11.2). Candida albicans represented the most common species (n = 35, 50.0%) followed by Candida glabrata (n = 15, 21.4%), Candida tropicalis (n = 6, 8.6%) and other yeasts (each < 5.0%). Incidence rate of C. albicans (2013: 7(78%); 2014: 10(59%); 2015: 6(35%); 2016: 12(44%)) and incidence rate of C. non-albicans (2013: 2(22%); 2014: 7(41%); 2015: 9(53%); 2016: 14(52%)) were different in trend. All fungal isolates were susceptible to echinocandins, amphotericin B and voriconazole. Regarding fluconazole susceptibility, C. krusei (n = 3) was resistant and C. glabrata (n = 9) was susceptible-dose dependent (SDD). The ratio of SDD C. glabrata isolates to all isolated C. glabrata strains was 9/15 (60%) (2013: 0/2; 2014: 0/2; 2015: 1/3; 2016: 8/8). Decreased fluconazole susceptibility for C. glabrata isolates was reported in both community-acquired IAC (n = 3) and hospital-acquired IAC (n = 6). Overall 30-day mortality rate was 25.0% (16/64). CONCLUSIONS: We have revealed slowly raising of overall IAC incidence, more increasing trend in incidence of community-acquired IAC compared to rather steady incidence of hospital-acquired IAC. During period 2013-2016 we have observed a significant shift in the aetiology of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates.

Genetic Markers at ANRIL, FTO and 2q36.3 Locus in Czech Patients Undergoing Coronary Artery Bypass Graft Surgery.

Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95 % CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.

The role of new antibiotics in intra-abdominal infections in the era of multi-resistant bacteria.

Complicated intra-abdominal infections (cIAI) are a substantial cause of morbidity at intensive care units. cIAI are frequently caused by multidrug-resistant strains of Enterobacteriaceae and Pseudomonas aeruginosa. In 592 cIAI patients from the First Department of Surgery, General University Hospital in Prague, we found an alarming increase in resistance of Escherichia coli to amoxicillin/clavulanic acid, piperacillin/tazobactam and third-generation cephalosporins in 2014-2017 (from 28.7% in 2014 to 37.5% in 2017, from 25% to 32% and from 2.3% to 5.6%, respectively). Ceftolozane/tazobactam and ceftazidime/avibactam are novel cephalosporins available for the treatment of cIAI. Ceftolozane/tazobactam is highly active against multidrug-resistant strains of P. aeruginosa, including carbapenem-resistant isolates. The new non-b-lactam b-lactamase inhibitor avibactam plus ceftazidime is active against carbapenemases-producing strains of Enterobacteriaceae. Both antibiotics are included in the new WSES guidelines for the management of cIAI.

Strong Association between APOA5 Gene Polymorphisms and Hypertriglyceridaemic Episodes.

Plasma triglyceride (TG) levels represent a significant risk factor of cardiovascular and total mortality. Concentrations of TG in the plasma depend, to a large extent, on the genetic background, and the apolipoprotein A5 (APOA5) gene seems to be one of the most powerful players in the plasma TG metabolism regulation. In total, we analysed three tagging APOA5 (rs964184 rs662799, rs3135506) SNPs in 209 patients with plasma TG levels over 10 mmol/l (HTG) on at least one occasion and in 379 treatment-naïve controls (NTG) with plasma TG values within the normal range. Minor alleles of all three analysed APOA5 polymorphisms significantly (all P < 0.0001) increased the risk of hypertriglyceridaemia. The most significant association (P < 0.0000001) was observed for the rs964184 polymorphism, where the minor GG homozygotes had the odds ratio (OR, 95% CI) for hypertriglyceridaemia development 21.30 (8.09-56.07, P < 0.000001) in comparison with the major CC allele homozygotes. Carriers of at least one minor allele at rs3135506 had OR (95% CI) 4.19 (2.75-6.40); (P < 0.000005) for HTG development and similarly, carriers of a minor allele at rs662799 had OR (95% CI) 3.07 (2.00-4.72) (P < 0.0001). The cumulative presence of risk alleles (unweighted gene score) significantly differed between patients with episodes of high TG and controls at P < 0.0000001. There were 73 % of subjects without any of the risk alleles among the controls and 46 % in the patients. In contrast, the controls just included 3 % of subjects with score 3 and more in comparison with 18 % in HTG patients. We conclude that common APOA5 variants are very important genetic determinants of episodic hypertriglyceridaemia in the Czech population with a high potential to be applied in personalized medicine.

Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations

Abstract Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others.

Polygenic hypercholesterolemia: examples of GWAS results and their replication in the Czech-Slavonic population.

Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analyzed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post-MONICA population sample (N=2,559). We confirmed an association (all P<0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males (N=1,194) and females (N=1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P<0.0005) and females (P<0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants.

Traditional risk factors of acute coronary syndrome in four different male populations - total cholesterol value does not seem to be relevant risk factor.

Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80+/-1.11 vs. 5.76+/-1.06 mmol/l in Czechs; 5.32+/-1.32 vs. 5.71+/-1.08 mmol/l in Lithuanians; 4.88+/-1.05 vs. 5.38+/-1.13 mmol/l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles.

Intake of carp meat from two aquaculture production systems aimed at secondary prevention of ischemic heart disease - a follow-up study.

Our previous study showed that a diet enriched with 400 g of carp per week improved plasma lipids in subjects after aortocoronary bypass (CABG). The aim of the present study is to determine whether the different carp farming systems have an impact on the effects of carp meat in secondary cardiovascular prevention. We examined 3 groups of patients after CABG over a 4-week period of spa treatment (108 persons, 73 males, 35 females, age over 60 years). We found no differences in baseline values of blood pressure or plasma lipids. The patients were given a standard spa diet (controls; N=36) or a diet enriched of 400 g of carp meat per week, enriched omega 3 (N=37) or cereal carp (N=35). Plasma lipid parameters were examined at start and after 4 weeks in a routine laboratory setting. Group consuming omega-3 carp showed the largest decline in total cholesterol, LDL cholesterol, triglycerides and an increase in HDL cholesterol (all p<0.01). We found that carp meat from the two production systems showed significantly different effects on plasma lipids. Further trials should be performed to clarify the exact causes of the differences.

SNPs within CHRNA5-A3-B4 and CYP2A6/B6 are associated with smoking dependence but not with tobacco dependence treatment outcomes in the Czech population.

PURPOSE: Tobacco/nicotine dependence has a significant heritable component. Genome-wide association studies have associated the single nucleotide polymorphisms (SNPs) rs578776, rs16969968, rs6474412, rs3733829 and rs4105144 with nicotine dependence in Western European populations. We examined whether these SNPs influence nicotine dependence and successful treatment of tobacco dependence in the Czech middle-European population. MATERIALS AND METHODS: Variants were analysed by PCR-RFLP or by TaqMan assay in 807 adult heavy tobacco-dependent smokers - patients of the Centre for Treatment of Tobacco Dependence (Prague) as well as 1,362 self-reported non-smokers. RESULTS AND DISCUSSION: Except for rs3733829, association with tobacco dependence was confirmed for all other genetic variants. In agreement with previous studies, the strongest determinant of tobacco dependence was rs16969968 with OR (95%CI) 1.32 (1.08-1.62) for A allele carriers vs. GG comparison (P=0.003). In contrast, none of the analysed variants reached significance with respect to a 1-year course of successful tobacco dependence treatment (all P over 0.18) in a subset of 525 patients. CONCLUSION: We confirmed the association between variants within genes that code nicotinic-acetylcholine receptors (-A3, -A5 and -B3), CYP2A6/B6 and tobacco dependence development in the Czech population. The success of the tobacco dependence treatment was not influenced by the analysed SNPs.

[Complicated intraabdominal infections in surgical patients-empiric antimicrobial therapy management]. / Komplikované nitrobrisní infekce u chirurgického nemocného - postup v empirické antimikrobní lécbe.

Any intraabdominal infection (IAI) is a complex disease that requires an assessment of a number of various aspectsimportant for determining proper therapeutic management, including an appropriate antimicrobial regimen. Current classifications of intraabdominal infections recognize various types of peritonitides (primary, secondary, tertiary); however, for clinical needs the cases are most commonly divided as non-complicated and complicated intraabdominal infections. In any intraabdominal infection, the surgical intervention includes perioperative empiric choice of antibiotics, which should take into account - in addition to the severity level of the infection - the epidemiological situation and risk factors of the presence of resistant bacteria in the patient. The article presents a current overview of the choice of antimicrobial agents indicated in individual groups of intraabdominal infections (biliary, extrabiliary) caused by community-acquired or hospital-acquired pathogens. Recent guidelines for choosing antimicrobial drugs against multiresistant bacteria provide very important information, particularly with respect to the increasing incidence of multiresistant strains as causal agents of intraabdominal infections in surgical patients. However, surgical departments need to be familiar with current sensitivity of pathogens in order to provide individualized antimicrobial therapy via empiric administration.Key words: intraabdominal infection multiresistant bacteria antimicrobial therapy.

[Characterisation of Candida sp. isolated from patients after abdominal surgery]. / Analýza záchytu kvasinek u pacientu po brisním chirurgickém výkonu.

INTRODUCTION: Intraabdominal candidiasis (IAC) is the predominant type of invasive candidiasis after candidemia. The majority of epidemiological studies on Candida are focused only on bloodstream infections. Nevertheless, the role of blood cultures has limited application in patients with abdominal candidiasis. IAC, which includes peritonitis and intraabdominal abscesses, may occur in around 40% of patients following repeat gastrointestinal (GI) surgery or GI perforation. METHOD: Retrospective analysis of culture isolates of Candida sp. from clinical specimens of patients after abdominal surgery. The study period was from January 1 to October 31, 2016. RESULTS: Our study of 33 patients with findings of Candida sp. from the abdominal cavity found a mortality of 15.2%, the most frequent strain being C. albicans and C. glabrata. All strains of Candida sp. were susceptible to echinocandins. CONCLUSIONS: Candida sp. is part of normal microbiota of the gastrointestinal tract and its isolation is often difficult to interpret. Unfortunately, the pathophysiologic importance of Candida isolation from the abdominal space is not completely clear in many clinical situations.Key words: invasive candidiasis intra-abdominal candidiasis laboratory diagnostics.

Large copy-number variations in patients with statin-associated myopathy affecting statin myopathy-related loci.

Some patients are susceptible to statin-associated myopathy (SAM) either because of genetic variations affecting statin uptake and metabolism, or because they predispose their carriers to muscular diseases. Among the frequent variants examined using the genome-wide association study approach, SLCO1B1 c.521T>C represents the only validated predictor of SAM in patients treated with high-dose simvastatin. Our aim was to ascertain the overall contribution of large copy-number variations (CNVs) to SAM diagnosed in 86 patients. CNVs were detected by whole genome genotyping using Illumina HumanOmni2.5 Exome BeadChips. Exome sequence data were used for validation of CNVs in SAM-related loci. In addition, we performed a specific search for CNVs in the SLCO1B region detected recently in Rotor syndrome subjects. Rare deletions possibly contributing to genetic predisposition to SAM were found in two patients: one removed EYS associated previously with SAM, the other was present in LARGE associated with congenital muscular dystrophy. Another two patients carried deletions in CYP2C19, which may predispose to clopidogrel-statin interactions. We found no common large CNVs potentially associated with SAM and no CNVs in the SLCO1B locus. Our findings suggest that large CNVs do not play a substantial role in the etiology of SAM.

The effect of colesevelam treatment on bile acid and lipid metabolism and glycemic control in healthy men.

The treatment of hypercholesterolemia with bile acid (BA) sequestrants results in upregulation of BA synthesis through the classical pathway initiated by cholesterol 7alpha-hydroxylase (CYP7A1). To characterize the detailed dynamics of serum lipid and BA concentrations and the BA synthesis rate in response to treatment with BA sequestrants and to determine whether the -203A/C promoter polymorphism of the CYP7A1 encoding gene (CYP7A1) affects such a response, this pilot study was carried out in healthy men (8 homozygous for the -203A allele and 8 homozygous for the -203C allele of CYP7A1). The subjects were treated for 28 days with colesevelam and blood was drawn for analysis before and on days 1, 3, 7, 14 and 28 of treatment. The response of lipids, BA, fibroblast growth factor-19 (FGF19) and 7alpha-hydroxy-4-cholesten-3-one (C4) to colesevelam did not differ between carriers of -203A and -203C alleles; their data were then aggregated for further analysis. Colesevelam treatment caused immediate suppression of FGF19 concentration and a fivefold increase in CYP7A1 activity, as assessed from C4 concentration, followed by a 17 % decrease in LDL-cholesterol. Although total plasma BA concentrations were not affected, the ratio of cholic acid/total BA rose from 0.25+/-0.10 to 0.44+/-0.16 during treatment at the expense of decreases in chenodeoxycholic and deoxycholic acid.