Familial occurrence of seizure disorders across MRI defined structural focal epilepsy etiology.

BACKGROUND: Previous studies have established familial occurrence of epilepsy and seizure disorders and early age of epilepsy onset as predictors of genetic epilepsy, but have not evaluated the rate of their occurrence in patients with different epilepsy etiology. Our study determines the distribution of familial occurrence and age of epilepsy onset across structural focal epilepsy (FE) etiology in a large FE cohort. METHODS: Records of 1354 consecutive patients evaluated for epilepsy and seizure disorders in The Neurology Clinic, University Clinical Center of Serbia from 2008 to 2019 were screened for FE. Structural etiology, lobar diagnosis, familial occurrence, and age at epilepsy onset were determined. Patients with a. nonlesional focal epilepsy (NLFE), b. hippocampal sclerosis (HS) and c. congenital or perinatal etiology (CPE) were classified as NAFE, while patients with an identified acquired focal epilepsy (AFE) constituted the control group. RESULTS: We identified 965 patients with FE, 329 (34.1 %) with NLFE, 213 (22.1 %) with HS, 174 (18.0 %) with CPE and 249 (25.8 %) with AFE. Familial occurrence was identified in 160 (16.6 %), 19.1 % of patients with NAFE and 9.2 % of AFE (p = 0.003). Patients with NAFE had a younger age of epilepsy onset (13 vs. 18 years, p < 0.001). The highest proportion of familial occurrence was found in patients with NLFE (23.7 %), while the youngest median age of epilepsy onset was identified in patients with HS (12 years) and CPE (11 years). CONCLUSION: Patients with NAFE frequently have familial occurrence of epilepsy and have an earlier age of epilepsy onset than patients with AFE.

Personal stethoscope disinfection practices and bacterial contamination: A cross-sectional study at the University Hospital Emergency Department in Belgrade, Serbia.

BACKGROUND: A significant reduction in bacterial growth on stethoscope membranes has been noticed after performing daily disinfection. Nevertheless, disinfection is rarely performed. We aimed to assess self-reported stethoscope disinfection practices among medical doctors, detect bacterial contamination on personal stethoscopes, and estimate the effectiveness of 70% ethanol as a stethoscope disinfecting agent. METHODS: To determine stethoscope disinfection practices, participants filled out a questionnaire (N = 47), followed by providing stethoscopes for bacterial analysis. Differences in bacterial contamination were observed through the self-reported frequency and method of stethoscope disinfection. The effect of disinfecting with 70% ethanol was evaluated by comparing the presence of bacterial growth before and after disinfection. RESULTS: The presence of bacterial growth was found in 78.7% of the stethoscope samples, with the median (interquartile range) number of colony-forming units at 25 (10-105). The frequency of disinfection greatly impacted the number of colony-forming units, and the method affected the presence of bacterial growth. Disinfection of stethoscope membranes using 70% ethanol resulted in a compelling 97.3% reduction of bacterial growth. CONCLUSIONS: Adequate stethoscope disinfection is highly efficient in reducing bacterial contamination and as such should be considered a critical step in hygienic practices.

Percutaneous Computed Tomography-Guided Oxygen-Ozone (O2O3) Injection Therapy in Patients with Lower Back Pain-An Interventional Two-Year Follow-Up Study of 321 Patients.

OBJECTIVES: To assess the effect of oxygen-ozone therapy guided by percutaneous Computed Tomography (CT) compared to corticosteroids in individuals experiencing lower back pain (LBP) not attributed to underlying bone-related issues. METHODS: A total of 321 patients (192 males and 129 females, mean age: 51.5 ± 15.1 years) with LBP were assigned to three treatment groups: group A) oxygen-ozone only, group B) corticosteroids only, group C) oxygen-ozone and corticosteroids. Treatment was administered via CT-guided injections to the intervertebral disc (i.e., intradiscal location). Clinical improvement of pain and functionality was assessed via self-reported pain scales and magnetic resonance (MR) and CT imaging. RESULTS: At all follow-up times, the mean score of the numeric rating scale and the total global pain scale (GPS) of study groups receiving oxygen-ozone (groups A and C) were statistically significantly lower than the study group receiving corticosteroids only (group B), with p < 0.001. There was a statistically significant difference between groups A and C at 30 days for the numeric rating scale. CONCLUSIONS: The percutaneous application of oxygen-ozone in patients with LBP due to degeneration of the lumbosacral spine showed long-lasting significant pain reduction of up to two years post-treatment when compared to corticosteroids alone. Combination therapy of oxygen-ozone and corticosteroids can be useful as corticosteroids showed statistically significant improvement in LBP earlier than the oxygen-ozone-only treatment.

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19.

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 109/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.

Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID.

Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations.

Atrial fibrillation is associated with poor long-term outcome after mechanical thrombectomy for anterior large vessel occlusion stroke.

OBJECTIVES: Atrial fibrillation (AF) is one of the leading causes of acute ischemic stroke (AIS). The aim of our study was to determine the influence of AF on the long-term outcome of patients with AIS due to anterior circulation large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). METHODS: Our study included 127 consecutive patients with AIS due to anterior LVO who underwent MT between January 2018 and March 2020. Demographics, clinical, radiological and treatment characteristics were prospectively collected. Modified Rankin scale (mRS) score ≤2 was defined as a good functional outcome. RESULTS: AF was detected in 62 (48.8%) patients. Patients with AF were elder (73.1 ± 8.7 vs. 58.5 ± 14.2 years, p<0.01) and usually female (56.5% vs. 36.9%, p=0.03). They had a lower percentage of good functional outcome (31.6% vs. 62.3%, p<0.01) and a higher mortality rate (47.5% vs. 18.5%, p<0.01) after one year of follow-up. In the multivariate logistic regression the variables that showed significance with p <0.05 in previous univariate analyses were included. The presence of AF (aOR 0.29, 95% CI 0.11-0.78, p=0.01) and initial NIHSS score >15 (aOR 0.25, 95% CI 0.11-0.56, p<0.01) were independent negative predictors of good functional outcome after one year of follow-up. However, the presence of AF did not affect all-cause mortality within one year (p=0.18). CONCLUSION: AF and initial NIHSS score >15 are independent negative predictors of good long-term functional outcome in patients with AIS due to anterior circulation LVO treated with MT.

Seroprevalence in health care workers during the later phase of the second wave: Results of three hospitals in Serbia, prior to vaccine administration.

BACKGROUND: Since the COVID-19 pandemic has started, Serbia has faced problems in implementing proper public health measures in the population, including non-pharmaceutical interventions, as well as protecting health care workers (HCWs) from disease, like all other countries. This study aimed to estimate COVID-19 seroprevalence and evaluate the risk perception of COVID-19 among HCWs in three different hospitals in Belgrade, Serbia: non-COVID hospital, Emergency Center (EC), and dedicated COVID hospital. METHODS: A cross-sectional study was conducted in three hospitals during the second wave of the outbreak in Serbia, from June to early October. All staff in these hospitals were invited to voluntarily participate in blood sampling for IgG antibodies against SARS-CoV-2 and questionnaire testing. The questionnaire included socio-demographic characteristics, known exposure to COVID-19 positive persons, previous signs and symptoms related to COVID-19 infection since the outbreak had started in our country, and SARS-CoV-2 PCR testing. RESULTS: The overall prevalence of SARS-CoV-2 antibody among 1580 HCWs was 18.3 % [95 % CI 16.4-20.3 %]. Significantly higher prevalence of HCWs with positive results for the serum IgG antibody test was observed in COVID hospital (28.6 %, 95 %CI: 24.0-33.6 %) vs. prevalence in the EC (12.6 %, 95 %CI: 10.1-15.4 %), and in the non-COVID hospital (18.3 %, 95 %CI: 15.2-26.7 %). The prevalence adjusted for declared test sensitivity and specificity would be 16.8 %; that is 27.4 % in COVID-19 hospital, 10.9 % in EC, and 16.8 % in non-COVID hospital. In multivariate logistic regression analysis, the independent predictors for seropositivity were working in COVID-hospital, the profession of physician, and the presence of the following symptoms: fever, shortness of breath, and anosmia/ageusia. CONCLUSIONS: We found an overall seropositivity rate of 18.3 % and 16.0 % of the adjusted rate that is higher than seroprevalence obtained in similar studies conducted before vaccinations started. The possibility that patients in non-COVID dedicated hospitals might also be infectious, although PCR tested, imposes the need for the use of personal protective equipment also in non-COVID medical institutions.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.

Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox-idant therapy.

GSTO1, GSTO2 and ACE2 Polymorphisms Modify Susceptibility to Developing COVID-19.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of ACE2 and glutathione transferase omega (GSTO) polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in ACE2 (rs4646116), GSTO1 (rs4925) and GSTO2 (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method. The data obtained showed that individuals carrying variant GSTO1*AA and variant GSTO2*GG genotypes exhibit higher odds of COVID-19 development, contrary to ones carrying referent alleles (p = 0.044, p = 0.002, respectively). These findings are confirmed by haplotype analysis. Carriers of H2 haplotype, comprising GSTO1*A and GSTO2*G variant alleles were at 2-fold increased risk of COVID-19 development (p = 0.002). Although ACE2 (rs4646116) polymorphism did not exhibit a statistically significant effect on COVID-19 risk (p = 0.100), the risk of COVID-19 development gradually increased with the presence of each additional risk-associated genotype. Further studies are needed to clarify the specific roles of glutathione transferases omega in innate immune response and vitamin C homeostasis once the SARS-CoV-2 infection is initiated in the host cell.

Influence of Thrombocytopenia on the Outcome of Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

OBJECTIVES: Mechanical thrombectomy (MT) has become leading treatment option for acute ischemic stroke (AIS) due to large vessels occlusion (LVO). Platelet counts may affect outcome in patients with AIS or transient ischemic attack. The aim of our study was to determine the influence of thrombocytopenia on the safety and efficacy of MT in patients with AIS due to anterior circulation LVO. MATERIALS AND METHODS: This study included 127 consecutive adult patients with AIS due to anterior circulation LVO who underwent MT. The patients were divided into 2 groups based on initial platelet count: with thrombocytopenia (<150 × 109/L) and without thrombocytopenia (≥150 × 109/L). Primary safety outcome was symptomatic intracerebral haemorrhage (SICH), while secondary safety outcome was stroke-related mortality. Efficacy outcome was functional independence, defined as modified Rankin Scale (mRS) score 0-2. Follow- up time was 90 days. RESULTS: Initial thrombocytopenia (<150 × 109/L) was detected in 19 (15%) patients. Multivariable analysis showed that initial thrombocytopenia did not increase the risk of SICH and did not affect the short-term functional outcome (p = 0.587). However, initial thrombocytopenia increased the risk for stroke-related mortality (aOR 3.639, 95% CI 1.079-12.641, p = 0.037). The main cause of mortality in the group with thrombocytopenia was malignant cerebral infarction (44.4%). CONCLUSIONS: Thrombocytopenia does not affect the efficacy and the risk of SICH in patients with AIS caused by anterior circulation LVO treated with MT. However, the risk of mortality is higher in patients with thrombocytopenia, mainly due to malignant cerebral infarction.

Glutathione S-Transferase Polymorphisms and Clinical Characteristics in Autism Spectrum Disorders.

Background: Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD. Methods: The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI). Results: It was shown that the GSTA1 * CC genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life. GSTM1-active genotype predicted a higher adaptive functioning. The predictive effect of GSTA1, GSTM1, and GSTT1 genotype was moderated by exposure during pregnancy (maternal smoking and medication). The GSTP1 * IleIle genotype was significantly associated to a better cognitive functioning in children with ASD. Conclusion: Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19.

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

Autism Spectrum Disorders and Perinatal Complications-Is Oxidative Stress the Connection?

Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD [odds ratio (OR) = 9.415; p = 0.000], as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.

Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of complex psychiatric disorders, with a proposed gene-environment interaction in their etiology. One mechanism that could explain both the genetic and environmental component is oxidative stress. The aim of our study was to investigate the potential role of common polymorphisms in genes for glutathione transferase A1, M1, T1 and P1 in susceptibility to ASD. We also aimed to explore the possible oxidative stress - specific gene-environment interaction, regarding GST polymorphisms, maternal smoking tobacco during pregnancy (TSDP) and the risk of ASD. This case-control study included 113 children with ASD and 114 age and sex-matched controls. The diagnosis was made based on ICD-10 criteria and verified by Autism Diagnostic Interview - Revised (ADI-R). We investigated GSTA1, GSTM1, GSTP1 and GSTT1 genotypes and explored their individual and combined effects in individuals with ASD. Individual effect of GST genotypes was shown for GSTM1 active genotype decreasing the risk of ASD (OR = 0.554, 95%CI: 0.313-0.983, p = 0.044), and for GSTA1 CC genotype, increasing susceptibility to ASD (OR = 4.132, 95%CI: 1.219-14.012, p = 0.023); the significance was lost when genotype-genotype interactions were added into the logistic regression model. The combination of GSTM1 active and GSTT1 active genotype decreased the risk of ASD (OR = 0.126, 95%CI: 0.029-0.547, p = 0.006), as well as combination of GSTT1 active and GSTP1 llelle (OR = 0.170, 95%CI: 0.029-0.992, p = 0.049). Increased risk of ASD was observed if combination of GSTM1 active and GSTP1 llelle was present (OR = 11.088, 95%CI: 1.745-70.456, p = 0.011). The effect of TSDP was not significant for the risk of ASD, neither individually, nor in interaction with specific GST genotypes. Specific combination of GST genotypes might be associated with susceptibility to ASD, while it appears that maternal smoking during pregnancy does not increase the risk of ASD.

Strengthening Emergency Care Systems to Mitigate Public Health Challenges Arising from Influxes of Individuals with Different Socio-Cultural Backgrounds to a Level One Emergency Center in South East Europe.

Emergency center visits are mostly unscheduled, undifferentiated, and unpredictable. A standardized triage process is an opportunity to obtain real-time data that paints a picture of the variation in acuity found in emergency centers. This is particularly pertinent as the influx of people seeking asylum or in transit mostly present with emergency care needs or first seek help at an emergency center. Triage not only reduces the risk of missing or losing a patient that may be deteriorating in the waiting room but also enables a time-critical response in the emergency care service provision. As part of a joint emergency care system strengthening and patient safety initiative, the Serbian Ministry of Health in collaboration with the Centre of Excellence in Emergency Medicine (CEEM) introduced a standardized triage process at the Clinical Centre of Serbia (CCS). This paper describes four crucial stages that were considered for the integration of a standardized triage process into acute care pathways.

Long-Term Prognosis in Ischemic Stroke Patients Treated with Intravenous Thrombolytic Therapy.

BACKGROUND AND PURPOSE: It remains unclear if intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator has an impact on the survival and maintenance of a favorable effect on functional recovery over a long follow-up period. The aim of this study was to assess whether or not IVT treatment has a favorable effect on functional recovery and survival less than 1 year after a stroke. METHODS: This matched cohort study included 259 patients with acute ischemic stroke (IS) who were treated with IVT and standard care and 259 patients treated with standard care alone in the stroke unit between February 2006 and January 2013. RESULTS: After a median follow-up period of 3 years (range, 1-7 years), survival did not differ significantly between the groups; specifically, 56 patients (21.6%) in the thrombolysed group died versus 62 patients (23.94%) in the nonthrombolysed group (log-rank, .240, P = .624). Based on a multivariate Cox proportional hazards regression model, older age (>70 years), stroke severity (National Institutes of Health Stroke Scale score ≥ 15), diabetes mellitus, and a history of atrial fibrillation were independent predictors of long-term mortality after stroke. After the follow-up period, 144 patients (55.6%) in the IVT-treated group versus 112 patients (43.2%) in the control group had an excellent outcome, with a modified Rankin Scale score of 0-1 (hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.16-2.32). Based on a multivariate Cox proportional hazards regression model, an excellent 3-month functional recovery was a strong predictor of favorable outcome (HR = 11.27, 95% CI = 6.45-19.63). CONCLUSION: The results suggest that IVT for acute IS has a favorable effect on functional recovery more than 1 year after stroke.

How to recognize and treat metabolic encephalopathy in Neurology intensive care unit.

Metabolic encephalopathy (ME) represents a syndrome of temporary or permanent disturbance of brain functions that occurs in different diseases and varies in clinical presentation. It can be manifested in a range from very mild mental disorders to deep coma and death. Clinically, it is characterized by a variety of psychiatric and neurological symptoms and signs. The most common causes of ME are: hypoxia, ischemia, systemic diseases and toxic agents. ME is the most frequent in elderly people who have previously been exhausted by chronic illnesses and prolonged stay in bed. ME is a very common complication in patients treated in intensive care units. Treatment and prognosis of the disease are varied and depend on aetiology, as well as on the type and severity of clinical presentation. Mortality of patients with septic encephalopathy ranges from 16-65%, while the one-year survival of patients with encephalopathy and liver cirrhosis is less than 50%.

Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study.

OBJECTIVE: To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. METHODS: We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews. RESULTS: Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. CONCLUSION: The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.

Return to Paid Work after Ischemic Stroke in Patients Treated with Intravenous Thrombolysis.

BACKGROUND: There are no available data confirming the efficacy of intravenous thrombolytic (IVT) treatment on the return to work as one of important outcome measure after acute ischemic stroke (IS). The aim of this study was to analyze the influence of IVT treatment on the return to work after stroke. METHODS: This matched cohort study included 279 patients with acute IS (146 treated with IVT and 133 matched patients without IVT) admitted to the Stroke Unit between 2007 and 2013. All patients were working in paid employment immediately before stroke onset. The main outcome measure was return to full-time paid work during follow-up period. RESULTS: After a median follow-up period of 3 years (range 1-7 years), the prevalence of stroke survivors returning to paid work was 42.1% in the IVT group and 33.3% in the non-IVT group (hazard ratio 1.28, 95% CI 0.86-1.91), and IVT treatment was associated with a higher chance of returning to full-time jobs (OR 2.07, 95% CI 1.21-3.51). After adjustment for possible variables, IVT was an independent predictor of returning to full-time jobs. CONCLUSION: IVT treatment was a positive predictor of returning to full-time work after stroke.