Olivera Djuric

Risk factors for ventilator-associated pneumonia in patients with severe traumatic brain injury in a Serbian trauma centre

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 r(2)=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.

Renewable energy sources and energy efficiency for building's greening: From traditional village houses via high-rise residential building's BPS and RES powered co- and tri-generation towards net ZEBuildings and Cities

As an introduction to the current approaches to buildings greening and sustainability this paper outlines the intrinsic harmony of the traditional village houses encompassing efficiency and balanced use of renewable materials and energy sources. Further paper reviews technical advances in integrating energy efficiency, solar and other renewable energy sources in new and existing buildings, to approach sustainable net Zero Energy Buildings, villages and cities. Paper stresses importance of the BPS (Building Performance Simulation) and Co-simulation in developing reliable method/engineering procedures for RES co-utilization and interwoven “energy mix” scenarios optimization, including existing buildings RES integrated refurbishment. Finally, presented are study results on the technical feasibility of efficient/cost-effective use of relatively low temperature geothermal waters for co- and tri-generation of electricity and heat for heating and/or cooling by absorption refrigeration for building integration. As a result of global warming a need for air-conditioning is in extreme growth in Central and Southeastern Europe, as well as in many other regions in the world rich in low temperature geothermal waters &#60;100°C (&#60;212°F), and there is a growing interest to utilize these waters in an efficient and cost effective way. It is well known that Kalina thermodynamic cycle can convert relatively low temperature energy, at relatively low temperature difference towards environment, to mechanical power and further to electricity using as a working fluid mixture comprised of at least two different components (water and ammonia). However, its co-generation efficiency at the heat source temperatures below and about 100°C is too low. That was the reason to explore technical possibilities to expand the low-temperature Kalina cycles geo-water utilization for co- and tri-generation based on the co-utilization - hybridization of geothermal with solar or other renewable energy sources (RES).

Mitotic crossover - an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma

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.

Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients

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.Genet Med advance online publication 10 November 2016

Oxidative stress markers predict early left ventricular systolic dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention

BACKGROUND Despite successful primary percutaneous coronary intervention (PCI) after ST-segment elevation myocardial infarction (STEMI), some patients develop left ventricular systolic dysfunction (LVSD) and acute heart failure (HF). Identifying patients with an increased risk of developing LVSD by means of biomarkers may help select patients requiring more aggressive therapy. OBJECTIVES The aim of this study was to evaluate the relationship between the levels of oxidative stress markers and development of LVSD and acute HF early after STEMI. MATERIAL AND METHODS The study enrolled 148 patients with the first STEMI, who were treated by primary PCI < 12 h from the onset of symptoms. We assessed the impact of different biomarkers for developing LVSD and acute HF (Killip ≥ 2) including: markers of necrosis - peak creatine kinase (CK), markers of myocardial stretch - B-type natriuretic peptide (BNP), inflammatory markers - C-reactive protein (CRP), leucocyte and neutrophil count, as well as oxidative stress markers - total thiol groups, catalase, superoxide dismutase (SOD) and glutathione reductase (GR). RESULTS In multivariate analysis, thiol groups, peak CK, anterior wall infarction, and age were predictors of LVEF ≤ 40%. Out of 16 variables significantly associated with the Killip ≥ 2 in univariate logistic regression analysis, 5 appeared to be independently associated with acute HF in multivariate analysis: catalase, BNP, leucocytes, neutrophil count, and size of left atrium. CONCLUSIONS In this study, we have shown for the first time that thiol groups and catalase are independent predictors of STEMI complication - LVSD and acute HF, respectively. Beside routine used biomarkers of necrosis and myocardial stretch, thiol groups and catalase may provide additional information regarding the risk stratification.

Twenty-eight-day mortality of blunt traumatic brain injury and co-injuries requiring mechanical ventilation

Objective: This paper aims to assess the impact of co-injuries and consequent emergency surgical interventions and nosocomial pneumonia on the 28-day mortality of patients with severe traumatic brain injuries (TBIs). Subjects and Methods: One hundred and seventy-seven patients with TBI admitted to the emergency trauma intensive care unit at the Clinical Center of Serbia for more than 48 h were studied over a 1-year period. On admission, the Glasgow Coma Scale (GCS), Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation II score (APACHE II) were calculated. At admission, an isolated TBI was recorded in 45 of the patients, while 44 had three or more co-injuries. Results: Of the 177 patients, 78 (44.1%) died by the end of the 28-day follow-up period. They had a significantly higher ISS score (25 vs. 20; p = 0.024) and more severe head (p = 0.034) and chest (p = 0.013) injuries compared to those who survived. Nonsurvivors had spent more days on mechanical ventilation (9.5 vs. 8; p = 0.041) and had a significantly higher incidence of ventilator-associated pneumonia (VAP) than survivors (67.9 vs. 40.4%; p < 0.001). A high Rotterdam CT score (OR 2.062; p < 0.001) and a high APACHE II score (OR 1.219; p < 0.001) were identified as independent predictors of early TBI-related mortality. Conclusion: Patients who had TBI with a high Rotterdam score and a high APACHE II score were at higher risk of 28-day mortality. VAP was a very common complication of TBI and was associated with an early death and higher mortality in the subgroup of patients with a GCS ≤8.

Agreement between CDC/NHSN surveillance definitions and ECDC criteria in diagnosis of healthcare-associated infections in Serbian trauma patients

After three national point prevalence studies (PPS) of healthcare associated infections (HAI) conducted in Serbian acute care hospitals using US (CDC/NHSN) surveillance definitions, Serbia is about to switch to European (ECDC) criteria for the purpose of the fourth HAI PPS. The aim of this study was to compare the US and the European HAI definitions in Serbian trauma intensive care unit (ICU). Prospective surveillance was performed at two surgical-trauma ICUs of the Emergency department of Clinical Center of Serbia. HAIs were prospectively diagnosed by experienced clinician and epidemiologists using both types of HAI definitions simultaneously. The level of agreement between two case definitions was assessed by Cohen’s kappa statistic (k). Of 406 patients, 107 (26.3%) acquired at least one HAI (total of 107 according to US definitions and 141 according to European criteria). For microbiologically confirmed pneumonia agreement was k = 0.99 (95% CI, 0.96–1.00) and for clinically defined k = 0.86 (95% CI, 0.58–1.00). Agreement for bloodstream infections (BSI) was 0.79 (CI 95%, 0.70–0.89). When secondary BSI was excluded from the European classification, (30.9% of all BSI), concordance was k = 1.00 and when microbiologically confirmed catheter related BSI were reported separately as recommended by latest ECDC protocol update, (20.0% of all BSI), concordance was 0.60 (CI 95%, 0.41–0.80). No agreement was found between CLABSI and CRI while slight agreement was found when compared CLABSI and CRI3 (k = 0.11; 95%CI, 0.0–0.22). Agreement for overall UTI was moderate (k = 0.66; 95%CI, 0.53–0.79) while for microbiologically-confirmed symptomatic UTI was perfect (k = 1.00). For CAUTI good agreement was observed (k = 0.77; 95%CI, 0.34–1.0). Microbiological confirmation of PN and UTI should be stimulated and comparison of BSI should be done with emphasis on whether secondary BSI is included.

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

PurposeMowat–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.MethodsIn 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.ResultsAll 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.ConclusionKnowledge 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.

Knowledge about blood-borne pathogens and the prevalence of needle stick injuries among medical students in Serbia

Abstract Introduction 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. Methods 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. Results 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. Conclusions 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.

Prognostic value of soluble CD14-ST (presepsin) in diagnosis of ventilator-associated pneumonia and sepsis in trauma patients

Background/Aim. Presepsin (soluble CD14-subtype) is a fragment of CD14 produced in response to bacterial infections and a novel biomarker of pneumonia, sepsis and septic shock. The aim of this study was to compare sensitivity and specificity of persepsin, soluble CD14-subtype (sCD14-ST) with other biomarkers: procalcitonine (PCT), C-reactive protein (CRP) and leukocyte count (Le) in mechanically ventilated injured patients, as a marker of pneumonia, sepsis and septic shock. Methods. The prospective study was undertaken in trauma and surgery intensive care unit of the Emergency Center, the Clinical Center of Serbia from January to April 2013. The study included 39 trauma patients requiring mechanical ventilation, and who developed one of the following inclusion criteria: Systemic Inflammatory Response Syndrome (SIRS), ventilator associated pneumonia (VAP), sepsis and/or septic shock. On admission Acute Physiology and Chronic Health Evaluation II (APACHE II) Score and Injury Severity Score (ISS) were calculated. Seventy-two measurements of four biomarkers (presepsin, PCT, CRP and Le) were performed in 39 patients at the moments of diagnosis of SIRS, VAP, sepsis and/or septic shock (21 when SIRS diagnosis was established, 21 after the diagnosis of VAP, 18 at the moment of diagnosis of sepsis and the remaining 12 measurements were conducted while diagnosing the septic shock). The Sequential Organ Failure Assessment (SOFA) score was calculated at these points as well. Results. Patients were mainly severely injured (mean ISS = 24.2) and had moderately severe medical condition at admission (mean Apache II score, 14.5). Presepsin concentration significantly differed among all the four groups, except between sepsis and septic shock. The strongest positive correlation of presepsin evinced with PCT (r = 0.741, p < 0.001). The sCD14-ST indicated better performance in diagnosis of both VAP (AUC = 0.909) and sepsis (AUC = 0.899), compared to PCT (AUCs: 0.863, 0.885, respectively), CRP (AUCs: 0.703, 0.677, respectively) and Le (AUCs: 0.668, 0.700, respectively). Conclusion. This study revealed that sCD14-ST is a reliable biomarker for distinguishing sepsis severity. It also showed a good correlation with the infection development as well as worsening in injured patients.