Browsing by Author "Djuric, Olivera (56410787700)"

Introduction: We aimed to report the distribution and resistance patterns of eight invasive clinically relevant bacteria surveyed in the Clinical Center of Serbia (CCS) in Belgrade. Methodology: A total of 477 clinical blood stream isolates of Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. were collected in the period from January to December 2013. Antimicrobial susceptibility testing was performed using standard methods and interpreted using the Clinical and Laboratory Standards Institute (CLSI) breakpoint criteria. Results: Acinetobacter spp. was the most prevalent bacteria encountered (37%), followed by K. pneumoniae (25.7%). Multidrug resistance was observed in 92.5% of all isolates. Out of 177 strains of Acinetobacter spp., 97.7% were resistant to fluoroquinolones and carbapenems. Resistance to aminoglycosides, fluoroquinolones, and third-generation cephalosporins was 97.1%, 95.4%, and 95.8% among K. pneumoniae and 21.4%, 21.7%, and 31% among E. coli isolates, respectively. In total, 65.1% of K. pneumoniae and 12.1% of E. coli isolates were determined to be extended-spectrum beta-lactamase (ESBL) positive. High-level aminoglycoside resistance of E. faecalis was 71.4%, and glycopeptide resistance of E. faecium was 95%. Out of 66 strains of S. aureus, 63.4% were methicillin resistant. Conclusions: The majority of bloodstream isolates of clinically relevant bacteria in CCS were multidrug resistant. The biggest concerns are carbapenem-resistant Acinetobacter spp., K. pneumoniae, and P. aeruginosa; third-generation cephalosporin-resistant E. coli; vancomycin-resistant E. faecium; and methicillin-resistant S. aureus. Stricter measures of infection control and antibiotic use are needed. © 2016 Djuric et al.

Introduction: We aimed to report the distribution and resistance patterns of eight invasive clinically relevant bacteria surveyed in the Clinical Center of Serbia (CCS) in Belgrade. Methodology: A total of 477 clinical blood stream isolates of Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. were collected in the period from January to December 2013. Antimicrobial susceptibility testing was performed using standard methods and interpreted using the Clinical and Laboratory Standards Institute (CLSI) breakpoint criteria. Results: Acinetobacter spp. was the most prevalent bacteria encountered (37%), followed by K. pneumoniae (25.7%). Multidrug resistance was observed in 92.5% of all isolates. Out of 177 strains of Acinetobacter spp., 97.7% were resistant to fluoroquinolones and carbapenems. Resistance to aminoglycosides, fluoroquinolones, and third-generation cephalosporins was 97.1%, 95.4%, and 95.8% among K. pneumoniae and 21.4%, 21.7%, and 31% among E. coli isolates, respectively. In total, 65.1% of K. pneumoniae and 12.1% of E. coli isolates were determined to be extended-spectrum beta-lactamase (ESBL) positive. High-level aminoglycoside resistance of E. faecalis was 71.4%, and glycopeptide resistance of E. faecium was 95%. Out of 66 strains of S. aureus, 63.4% were methicillin resistant. Conclusions: The majority of bloodstream isolates of clinically relevant bacteria in CCS were multidrug resistant. The biggest concerns are carbapenem-resistant Acinetobacter spp., K. pneumoniae, and P. aeruginosa; third-generation cephalosporin-resistant E. coli; vancomycin-resistant E. faecium; and methicillin-resistant S. aureus. Stricter measures of infection control and antibiotic use are needed. © 2016 Djuric et al.

Purpose: Understanding target groups' awareness and knowledge regarding the human papillomavirus (HPV) and the HPV vaccine is essential for planning the screening and vaccination programs and attaining adequate vaccination coverage. The aim of this study was to estimate awareness and knowledge about HPV infection and the HPV vaccine and to assess factors associated with HPV awareness, HPV vaccine awareness and high HPV-related knowledge among women undergoing cervical cancer screening in Serbia. Methods: A cross-sectional study was conducted between January and June 2013 at the Obstetrics and Gynecology Clinic “Narodni Front” in Belgrade, Serbia. HPV awareness, HPV vaccine awareness, and HPV-related knowledge of women undergoing cervical cancer screening were estimated by the means of structured, self-administered questionnaire. Results: The median age of respondents was 36.0 years (range 18-65). Of 324 women participating in the study, 196 (60.5%) had heard of HPV while 95 (29.3%) had heard of the HPV vaccine. The median HPV-related knowledge score was 7 (interquartile range 4.8). Type of occupation and having an increasing number of lifetime sexual partners were associated with HPV awareness, while having no children was associated with HPV vaccine awareness. High HPV knowledge score was associated with younger age and type of occupation. Conclusions: Women undergoing cervical cancer screening in Serbia have moderate awareness of HPV infection and low awareness of HPV vaccine. However, it is promising that those who heard of HPV have high knowledge about it. © This work by JBUON is licensed under a Creative Commons Attribution 4.0 International License.

Purpose: Understanding target groups' awareness and knowledge regarding the human papillomavirus (HPV) and the HPV vaccine is essential for planning the screening and vaccination programs and attaining adequate vaccination coverage. The aim of this study was to estimate awareness and knowledge about HPV infection and the HPV vaccine and to assess factors associated with HPV awareness, HPV vaccine awareness and high HPV-related knowledge among women undergoing cervical cancer screening in Serbia. Methods: A cross-sectional study was conducted between January and June 2013 at the Obstetrics and Gynecology Clinic “Narodni Front” in Belgrade, Serbia. HPV awareness, HPV vaccine awareness, and HPV-related knowledge of women undergoing cervical cancer screening were estimated by the means of structured, self-administered questionnaire. Results: The median age of respondents was 36.0 years (range 18-65). Of 324 women participating in the study, 196 (60.5%) had heard of HPV while 95 (29.3%) had heard of the HPV vaccine. The median HPV-related knowledge score was 7 (interquartile range 4.8). Type of occupation and having an increasing number of lifetime sexual partners were associated with HPV awareness, while having no children was associated with HPV vaccine awareness. High HPV knowledge score was associated with younger age and type of occupation. Conclusions: Women undergoing cervical cancer screening in Serbia have moderate awareness of HPV infection and low awareness of HPV vaccine. However, it is promising that those who heard of HPV have high knowledge about it. © This work by JBUON is licensed under a Creative Commons Attribution 4.0 International License.

Introduction: We aimed to describe incidence, outcomes and antimicrobial resistance markers of causative agents of bacterial BSI in the intensive care unit (ICU) in a trauma center in Serbia. Methodology: Prospective surveillance was conducted from November 2014 to April 2016 in two trauma-surgical ICUs of the Emergency Department of Clinical center of Serbia. Bloodstream infections were diagnosed using the definitions of Center for Disease Control and Prevention. Results: Out of 406 trauma patients, 57 had at least one episode of BSI (cumulative incidence 14.0%). Overall 62 BSI episodes were diagnosed (incidence rate 11.8/1000 patient/days), of which 43 (69.4%) were primary BSI (13 catheter-related BSI and 30 of unknown origin) and 19 (30.6%) were secondary BSI. The most common isolated pathogen was Acinetobacter spp. [n = 24 (34.8%)], followed by Klebsiella spp. [n = 17 (24.6%)] and P. aeruginosa [n = 8 (1.6%)]. All S. aureus [n = 6 (100%)] and CoNS [n = 3 (100%)] isolates were methicillin resistant, while 4 (66%) of Enterococci isolates were vacomycin resistant. All isolates of Enterobacteriaceae were resistant to third-generation cephalosporins [n = 22 (100%)] while 7 (87.5%) of P. aeruginosa and 23 (95.8%) of Acinetobacter spp. isolates were resistant to carbapenems. All-cause mortality and sepsis were significantly higher in trauma patients with BSI compared to those without BSI (P < 0.001 each). Conclusions: BSI is a common healthcare-associated infection in trauma ICU and it is associated with worse outcome. Better adherence to infection control measures and guidelines for prevention of primary BSI must be achieved. © 2018 Djuric et al.

Introduction: We aimed to describe incidence, outcomes and antimicrobial resistance markers of causative agents of bacterial BSI in the intensive care unit (ICU) in a trauma center in Serbia. Methodology: Prospective surveillance was conducted from November 2014 to April 2016 in two trauma-surgical ICUs of the Emergency Department of Clinical center of Serbia. Bloodstream infections were diagnosed using the definitions of Center for Disease Control and Prevention. Results: Out of 406 trauma patients, 57 had at least one episode of BSI (cumulative incidence 14.0%). Overall 62 BSI episodes were diagnosed (incidence rate 11.8/1000 patient/days), of which 43 (69.4%) were primary BSI (13 catheter-related BSI and 30 of unknown origin) and 19 (30.6%) were secondary BSI. The most common isolated pathogen was Acinetobacter spp. [n = 24 (34.8%)], followed by Klebsiella spp. [n = 17 (24.6%)] and P. aeruginosa [n = 8 (1.6%)]. All S. aureus [n = 6 (100%)] and CoNS [n = 3 (100%)] isolates were methicillin resistant, while 4 (66%) of Enterococci isolates were vacomycin resistant. All isolates of Enterobacteriaceae were resistant to third-generation cephalosporins [n = 22 (100%)] while 7 (87.5%) of P. aeruginosa and 23 (95.8%) of Acinetobacter spp. isolates were resistant to carbapenems. All-cause mortality and sepsis were significantly higher in trauma patients with BSI compared to those without BSI (P < 0.001 each). Conclusions: BSI is a common healthcare-associated infection in trauma ICU and it is associated with worse outcome. Better adherence to infection control measures and guidelines for prevention of primary BSI must be achieved. © 2018 Djuric et al.

Objective The aim of the study was to assess the impact of human papillomavirus (HPV) awareness and knowledge on physiological state and quality of life of women referred to colposcopy and/or HPV testing. Materials and Methods A cross-sectional study was carried out at University Hospital, Belgrade, Serbia. The women with abnormal Pap test results obtained at the primary care centers requiring colposcopy and/or HPV testing were included. Before gynecological examination, participants filled the questionnaire on demographic characteristics, gynecological history, questionnaire for the evaluation of HPV awareness and HPV knowledge level, a set of self-report questionnaires assessing the anxiety level, quality of life, and concern about the smear and colposcopy results and perceived risk of developing cervical cancer. Results Of 324 women, 196 (60.5%) were aware of HPV. They reported higher concern about test results (p <.001), perceived risk of developing cervical cancer (p <.001), and had significantly lower quality of life (p =.004) than women who did not hear anything about this virus. On contrary, better knowledge correlated with younger age (p <.001) and better quality of life (p <.0001) and was associated with lower anxiety, lower concern about smear test results, and lower perceived risk of developing cancer. Conclusions Human papillomavirus awareness and knowledge have different impact on psychological state and quality of life. Being aware of HPV is not enough for reducing the stress and anxiety and increasing the coverage of screening. Therefore, it is necessary to increase women's knowledge through more detailed information about HPV in different public health messages and education programs. © 2018, ASCCP.

Introduction: Single nucleotide variants (SNVs) represent important genetic risk factors for susceptibility to posttraumatic sepsis and a potential target for immunotherapy. We aimed to evaluate the association between 8 different SNVs within tumor necrosis factor alpha (TNFA), lymphotoxin alpha (LTA) and Toll-like receptor (TLR2 and TLR4) genes and the risk of posttraumatic sepsis. Methods: Nested case-control study was conducted in the emergency department of the Clinical Centre of Serbia including 228 traumatized patients (44 with sepsis and 184 without sepsis). To compare the results of trauma subjects with the data from the general population, a control group of 101 healthy persons was included in the study. Genotyping of TNFA (rs1800629 and rs361525), LTA (rs909253), TLR2 (rs3804099, rs4696480 and rs3804100), and TLR4 (rs4986790 and rs4986791) was performed for all patients within all three groups using the real-time PCR method. MutationTaster database and in silico software SIFT were used to predict the variant pathogenic effect. Results: Carriage of the G allele of the TNFA rs1800629 gene variant (OR 2.1, 95%CI 1.06-4.16) and T allele-carriage of the TLR4 rs4986791 genetic variant (OR 3.02, 95%CI 1.31-6.57) were associated with significantly higher risk of sepsis in trauma patients when compared to the general population prone to sepsis and traumatized patients without developing a sepsis, respectively. Of these two variants, only variant in TLR4 gene (rs4986791) has been labeled as disease causing by both the MutationTaster database and the in-silico software SIFT, which further supports the role of this variant in various pathologies including sepsis. For the remaining six variants no significant association with the susceptibility to sepsis was detected. Conclusions: Carriage of the G allele of the TNFA rs1800629 gene variant and T allele-carriage of the TLR4 rs4986791 genetic variant confer significant risk of posttraumatic sepsis. TLR4 gene variants (rs4986790 and rs4986791) has been labelled as disease causing. © 2021 Elsevier Ltd

The data about the incidence and risk factors for surgical site infections (SSIs) following total joint arthroplasty (TJA) in middle-income countries are still scant. The aim of this study was to assess the incidence and risk factors associated with 30-day SSIs following total hip arthroplasty (THA) and total knee arthroplasty (TKA). The study was conducted at the Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Serbia (CCS) in Belgrade, from May 2016 to April 2018. All patients undergoing THA or TKA were followed throughout hospitalization until day 30 after discharge. Of the 1073 admitted patients, 459 had THA and 230 had TKA. The incidence rate of surgical site infections (SSIs) among the patients who underwent THA was 5.4%, which is 3.8 per 1000 postoperative patient-days, while the rate among those who had TKA was 4.8%, i.e., 3.4 per 1000 postoperative patient-days. Out of the 36 SSIs, 15 were deep and 21 were superficial incisional ones. Among the variables examined, the independent risk factors for SSIs after THA were the American Society of Anesthesiologists (ASA) score > 2 (RR = 3.17; 95% CI—1.26–8.02), smoking (RR = 3.14; 95% CI—1.26–7.82) and peripheral vascular disease (PVD) (RR = 6.09; 95% CI—2.35–15.77), and after TKA, only PVD (RR = 3.87; 95% CI—1.09–13.76) was the risk factor. Incidence rates of SSIs after arthroplasty are higher compared to reports from developed countries. Therefore, it is necessary to enhance infection prevention and control measures with strict control of modifiable risk factors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The data about the incidence and risk factors for surgical site infections (SSIs) following total joint arthroplasty (TJA) in middle-income countries are still scant. The aim of this study was to assess the incidence and risk factors associated with 30-day SSIs following total hip arthroplasty (THA) and total knee arthroplasty (TKA). The study was conducted at the Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Serbia (CCS) in Belgrade, from May 2016 to April 2018. All patients undergoing THA or TKA were followed throughout hospitalization until day 30 after discharge. Of the 1073 admitted patients, 459 had THA and 230 had TKA. The incidence rate of surgical site infections (SSIs) among the patients who underwent THA was 5.4%, which is 3.8 per 1000 postoperative patient-days, while the rate among those who had TKA was 4.8%, i.e., 3.4 per 1000 postoperative patient-days. Out of the 36 SSIs, 15 were deep and 21 were superficial incisional ones. Among the variables examined, the independent risk factors for SSIs after THA were the American Society of Anesthesiologists (ASA) score > 2 (RR = 3.17; 95% CI—1.26–8.02), smoking (RR = 3.14; 95% CI—1.26–7.82) and peripheral vascular disease (PVD) (RR = 6.09; 95% CI—2.35–15.77), and after TKA, only PVD (RR = 3.87; 95% CI—1.09–13.76) was the risk factor. Incidence rates of SSIs after arthroplasty are higher compared to reports from developed countries. Therefore, it is necessary to enhance infection prevention and control measures with strict control of modifiable risk factors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Medical students are mainly exposed to needle stick and sharp object injuries in the course of their clinical activities during studying. They are at high risk due to their undeveloped skills, restricted clinical experience, lack of knowledge and risk perception. The objectives of this study were to determine the prevalence of needle stick injuries of the fourth and final year medical students, and to estimate their knowledge about blood-borne pathogens disease transmission and standard precautions. This cross-sectional study was conducted at the Faculty of Medicine, in February 2014. The students were invited to self-administer a questionnaire of 26 closed questions prepared for this study. The questionnaire was filled in and returned by 637 students. The prevalence of needle sticks and sharp object injuries was 29.5%. Needle stick injuries were the most common type of accidents, more frequent among the fourth compared to the sixth year students (p=0.002). The majority of accidents occurred in patient rooms (53%) and the emergency department (15%). 54% of participants reported an accident to the responsible person. Students without accidents had a significantly better perception of risk (3.79 vs. 3.35; p<0.05). Out of the total participating students, only 16.6% (106/637) received all three doses of Hepatitis B vaccination, while 16.2% were partially vaccinated. There is a need for additional theoretical and practical education of our students on blood exposure via accidents, raising the awareness of the necessity of hepatitis B vaccination, and introducing the unique/comprehensive procedure for accident reporting for students and healthcare workers in the entire country. © National Institute of Public Health, Slovenia.

Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Background: Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children. Results: In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build. Conclusions: These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS. © 2020 The Author(s).

Purpose:Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined.Methods:Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations.Results:Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis.Conclusion:This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment. © 2016 American College of Medical Genetics and Genomics.

Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naïve SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p < 0.001), BAFF and DNase I concentration (p < 0.01). Contrary, NETolytic activity was lower in SLE patients (p < 0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p < 0.001, p < 0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p < 0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p < 0.01), cfDNA and BAFF levels (p < 0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p < 0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naïve SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naïve SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p < 0.001), BAFF and DNase I concentration (p < 0.01). Contrary, NETolytic activity was lower in SLE patients (p < 0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p < 0.001, p < 0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p < 0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p < 0.01), cfDNA and BAFF levels (p < 0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p < 0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naïve SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Purpose: Mowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS. Methods: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. Conclusion: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care. © 2018, American College of Medical Genetics and Genomics.

Purpose: To investigate the psychological effects of PAP smear and colposcopy performed simultaneously and receipt of abnormal tests' results on women's well-being and quality of life (QoL) using different relative questionnaires. Methods: A prospective cohort study included 324 women with abnormal PAP smear result obtained at the primary care centers, requiring repeat smear test and colposcopy in our hospital. Questionnaires regarding the patient demographic characteristics, 7-point Likert scales which indicate concern about the smear and colposcopy results and risk of developing cervical cancer, Bek Anxiety Inventory (BAI), European QoL questionnaire - Euro QoL (EQ-5D) and visual analogue scale (EQ VAS) were used. Women filled in the questionnaires at the pre-procedural assessment, and again, 7-10 days after testing, just after the reception of results. Results: According to BAI scale, almost one-quarter of women (23.5%) showed mild to severe anxiety; higher level of anxiety had women with abnormal test results (p=0.008). After adjustment for age, the difference reached statistical significance in the follow up period, too (p<0.05). At the pre-procedural assessment, there was no significant difference in the concern about test results (4.09 vs 4.22) and the perceived risk of developing cervical cancer (3.99 vs 4.14) using self-assessment by the Likart scales. However, women with abnormal test results had lower quality of life compared to women with normal PAP smear and colposcopy (mean EQ-VAS score 77.35 ± 15.63 vs 81.14 ± 16.07; p=0.020). Conclusions: We conclude that referral for evaluation after a first abnormal PAP test leads to anxiety. Close and clear communication about test meaning and its consequences is needed in the organized screening test.

Purpose: To investigate the psychological effects of PAP smear and colposcopy performed simultaneously and receipt of abnormal tests' results on women's well-being and quality of life (QoL) using different relative questionnaires. Methods: A prospective cohort study included 324 women with abnormal PAP smear result obtained at the primary care centers, requiring repeat smear test and colposcopy in our hospital. Questionnaires regarding the patient demographic characteristics, 7-point Likert scales which indicate concern about the smear and colposcopy results and risk of developing cervical cancer, Bek Anxiety Inventory (BAI), European QoL questionnaire - Euro QoL (EQ-5D) and visual analogue scale (EQ VAS) were used. Women filled in the questionnaires at the pre-procedural assessment, and again, 7-10 days after testing, just after the reception of results. Results: According to BAI scale, almost one-quarter of women (23.5%) showed mild to severe anxiety; higher level of anxiety had women with abnormal test results (p=0.008). After adjustment for age, the difference reached statistical significance in the follow up period, too (p<0.05). At the pre-procedural assessment, there was no significant difference in the concern about test results (4.09 vs 4.22) and the perceived risk of developing cervical cancer (3.99 vs 4.14) using self-assessment by the Likart scales. However, women with abnormal test results had lower quality of life compared to women with normal PAP smear and colposcopy (mean EQ-VAS score 77.35 ± 15.63 vs 81.14 ± 16.07; p=0.020). Conclusions: We conclude that referral for evaluation after a first abnormal PAP test leads to anxiety. Close and clear communication about test meaning and its consequences is needed in the organized screening test.

Introduction: The aims of this study were (1) to assess the incidence of ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI), (2) to identify risk factors for developing VAP, and (3) to assess the prevalence of the pathogens responsible. Patients and methods: The following data were collected prospectively from patients admitted to a 24-bed intensive care unit (ICU) during 2013/14: the mechanism of injury, trauma distribution by system, the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Abbreviated Injury Scale (AIS) score, the Injury Severity Score (ISS), underlying diseases, Glasgow Coma Scale (GCS) score, use of vasopressors, need for intubation or cardiopulmonary resuscitation upon admission, and presence of pulmonary contusions. All patients were managed with a standardized protocol if VAP was suspected. The Sequential Organ Failure Assessment (SOFA) score and the Clinical Pulmonary Infection Score (CPIS) were measured on the day of VAP diagnosis. Results: Of the 144 patients with TBI who underwent mechanical ventilation for >48h, 49.3% did not develop VAP, 24.3% developed early-onset VAP, and 26.4% developed late-onset VAP. Factors independently associated with early-onset VAP included thoracic injury (odds ratio (OR) 8.56, 95% confidence interval (CI) 2.05-35.70; p=0.003), ISS (OR 1.09, 95% CI 1.03-1.15; p=0.002), and coma upon admission (OR 13.40, 95% CI 3.12-57.66; p<0.001). Age (OR 1.04, 95% CI 1.02-1.07; p=0.002), ISS (OR 1.09, 95% CI 1.04-1.13; p<0.001), and coma upon admission (OR 3.84, 95% CI 1.44-10.28; p=0.007) were independently associated with late-onset VAP (Nagelkerke r2=0.371, area under the curve (AUC) 0.815, 95% CI 0.733-0.897; p<0.001). The 28-day survival rate was 69% in the non-VAP group, 45.7% in the early-onset VAP group, and 31.6% in the late-onset VAP group. Acinetobacter spp was the most common pathogen in patients with early- and late-onset VAP. Conclusions: These results suggest that the extent of TBI and trauma of other organs influences the development of early VAP, while the extent of TBI and age influences the development of late VAP. Patients with early- and late-onset VAP harboured the same pathogens. © 2015 The Authors.