Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory ...molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS, and has been associated in previous, smaller studies to increased disability and disease activity. CSF IL-6 detectability in MS 2 This is a provisional file, not the final typeset article Here, we wanted to further address IL-6 as a possible CSF biomarker of MS by investigating its detectability in a large cohort of 534 MS patients and in 100 individuals with other non-inflammatory neurological diseases. In these newly diagnosed patients, we also explored correlations between IL-6 detectability, MS phenotypes and disease characteristics.We found that IL-6 was more frequently detectable in the CSF of MS patients compared with their control counterparts, as significant differences emerged between patients with clinically isolated syndrome, relapsing remitting, secondary progressive and primary progressive MS, compared to noninflammatory controls. IL-6 was equally present in the CSF of all MS phenotypes. In MS patients, IL-6 detectability was found to signal clinically and/or radiologically defined disease activity, among all other clinical characteristics.Our results add further evidence that CSF proinflammatory cytokines could be useful for the identification of those MS patients who are prone to increased prospective disease activity. In particular, IL-6 could represent an interesting prognostic biomarker of MS, as also demonstrated in other diseases where CSF IL-6 was found to identify patients with worse disease severity.
Abstract Objective evaluation of etiology, clinical course and response to the treatment of status epilepticus (SE) in children, with particular investigation of superrefractory SE. Materials and ...methods The retrospective study included children with convulsive SE aged 0.2–18 years, treated from 1995 to 2011. Status epilepticus is defined as a continuous seizure or intermittent seizures without full recovery of consciousness between seizures for at least 30 min. Refractory SE is diagnosed if SE lasts for more than 60 min, while superrefractory SE if SE continues or recurs 24 h or more after the onset of an anesthesia therapy, including those cases that recur after reduction or withdrawal of an anesthesia. The etiology was summarized in five categories: idiopathic/cryptogenic, remote symptomatic, febrile SE, acute symptomatic and progressive encephalopathy. The patients were treated according to the same hospital protocol. Midazolam iv and diazepam rectally were given as the first line drugs, phenobarbital/phenytoin iv as the second line drugs. If they failed, third line drugs, midazolam and thiopental were given in continuous intravenous infusion. The medication was defined as effective if seizure clinically stopped within 20 min, without recurrence within the next 6 h. Midazolam was assessed as effective even if it failed as the first line, but was effective in intravenous infusion as the third line drug. Results The study consisted of 602 SE in 395 children. There were 305 (50.7%) refractory SE episodes, and 43 (7.1%) of superrefractory SE. Idiopathic/cryptogenic and febrile SE was the most common etiology in the first SE, while progressive encephalopathy and remote symptomatic was in recurrent and superrefractory SE. The most effective drugs were: midazolam (306/339) given in mean dose of 0.4 mg/kg (range 0.1–1.2 mg/kg), thiopental (47/57) in mean dose of 4 mg/kg (range 3–5 mg/kg), phenobarbital (91/135) in dose of 20 mg/kg. Midazolam successfully stopped 306/339 SE episodes (90.3%), 67 SE (21.9%) by equal or lower dose than 0.2 mg/kg as the first line drug, while all other 239 episodes (78.9%) were stopped by intravenous infusion in range 0.2–1.2 mg/kg/h (mean 0.4 mg/kg/h) as the third line drug. Adverse effects were frequent in superrefractory SE (60.5%). In 15 patients, corticosteroids contributed to the reduction of seizure recurrence after anesthetic withdrawal and cessation of epilepsia partialis continua. Case fatality rate was 5.1% in all patients, while 21.3% in patients with superrefractory SE. Conclusion Status epilepticus in children was characterized by heterogeneous etiology, prolonged duration and commonly good response to midazolam only given in high doses. Superrefractory SE was not so rare in children, especially among the patients with progressive encephalopathy.
The aim of the study was to evaluate the presenting symptoms and signs of idiopathic intracranial hypertension (IIH) in a large cohort of patients and to estimate their possible role in establishing ...the diagnosis of IIH.
This prospective cohort study in two tertiary centers, the Danish Headache Center in Rigshospitalet-Glostrup and the Neurology Clinic of the Clinical Center of Serbia, included 286 patients referred by attending specialists for possible IIH evaluation. Patients were divided into two groups: one with confirmed IIH diagnosis and one with rejected IIH diagnosis.
The diagnosis of IIH was confirmed in 219 (76.6%) patients. It was more often confirmed if the patient was referred by an ophthalmologist than if the referral was from a neurologist (83.6% vs. 69.8%, p = .029) and in patients with higher body mass index (BMI) (p = .032). Transient visual obscurations (p = .006), double vision (p = .033), neck pain (p = .025), and tinnitus (p = .013) were presenting symptoms more frequently reported by patients with IIH diagnosis. In the same group of patients, papilledema (p < .001) and sixth nerve palsy (p = .010) were noted significantly more often. Papilledema was extracted by multivariate analysis as an independent predictor of IIH diagnosis (p < .001).
Although studies investigating IIH report an abundance of presenting symptoms, our results indicate that these symptoms are not diagnostic for IIH. Papilledema is the most reliable clinical sign predicting the correct IIH diagnosis in patients with suspected IIH.
•Visual disturbances, tinnitus, neck pain and obesity are common findings in IIH.•Presenting symptoms do not predict correct diagnosis in patients with suspected IIH.•Papilledema is the most reliable clinical sign predicting IIH diagnosis.
Multiple Sclerosis Spasticity Scale (MSSS)-88 has been developed for self-assessment of spasticity symptoms in patients with multiple sclerosis (MS). The objective of this study was to validate ...MSSS-88 and evaluate the psychometric properties in patients with MS in Serbia.
The study comprised 65 MS patients with spasticity. MSSS-88 consists of 88 items grouped in eight sections. Internal consistency of the MSSS-88SR subscales was determined using Cronbach's alpha coefficient. Test/retest reliability with an intra-class correlation coefficient (ICC) for each MSSS-88SR subscale was performed. Clinical validity of MSSS-88SR was determined by correlations with the Numeric Rating Scale (NRS) and the Modified Ashworth Scale (MAS).
The range of Cronbach's alpha for all scales and ICC was 0.91-0.96 and 0.84-0.91, respectively. All ICCs were statistically significant (p<0.05). All evaluated subscales of MSSS-88 were significantly correlated with the NRS scale. The highest correlation coefficients were registered between the WL subscale and the EDSS and MAS, while the strongest relationship was observed between the MSS subscale and the NRS.
The Serbian translated version of this instrument may be useful as a clinical measure for spasticity and functionality in patients with MS.
: Despite improvements in screening programs, a large number of patients with colorectal cancer (CRC) are diagnosed in an advanced disease stage. Previous investigations imply that glutathione ...transferases (GSTs) might be associated with the development and progression of CRC. Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs. The aim of this study was to evaluate the significance of certain
genetic variants on CRC prognosis and the efficacy of oxaliplatin-based treatment.
: This prospective study included 523 patients diagnosed with CRC in the period between 2014 and 2016, at the Digestive Surgery Clinic, University Clinical Center of Serbia, Belgrade. Patients were followed for a median of 43.47 ± 17.01 months (minimum 1-63 months). Additionally, 109 patients with advanced disease, after surgical treatment, received FOLFOX6 treatment as a first-line therapy between 2014 and 2020. The
-
method was used to analyze cumulative survival, and the Cox proportional hazard regression model was used to study the effects of different
genotypes on overall survival.
: Individuals with the
genotype and the
(
genotype had significantly shorter survival when compared to referent genotypes (
and
) (log-rank:
= 0.001). Moreover, individuals with the
genotype who received 5-FU-based treatment had statistically significantly shorter survival when compared to individuals with the
(log-rank:
= 0.05).
: Both GSTM1-null and GSTP1 IleVal+ValVal (
) genotypes are associated with significantly shorter survival in CRC patients. What is more, the
genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.
Progressive supranuclear palsy (PSP) and parkinsonian subtype of multiple system atrophy (MSA-P) are, after Parkinson’s disease (PD), the most common forms of neurodegenerative parkinsonism. Clinical ...heterogeneity of PSP includes two main variants, Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P). Clinical differentiation between them may be impossible at least during the first 2 years of the disease. Little is known about the differences in natural course of PSP-RS and PSP-P and, therefore, in this study we prospectively followed the clinical outcomes of consecutive, pathologically unconfirmed patients with the clinical diagnoses of PSP-RS (51 patients), PSP-P (21 patients) and MSA-P (49 patients). Estimated mean survival time was 11.2 years for PSP-P, 6.8 years for PSP-RS, and 7.9 years for MSA-P, where a 5-year survival probabilities were 90, 66 and 78 %, respectively. More disabling course of PSP-RS compared to PSP-P was also highlighted through the higher number of milestones reached in the first 3 years of the disease, as well as in the trend to reach all clinical milestones earlier. We found that PSP-P variant had a more favorable course with longer survival, not only when compared to PSP-RS, but also when compared to another form of atypical parkinsonism, MSA-P.
Objective
The aim of this study was to investigate the level of burnout and identify who is at highest risk among healthcare professionals (HCPs) working at the largest referent national institution.
...Methods
A cross-sectional survey was conducted at the Institute of Oncology and Radiology of Serbia from May 2019 to July 2019, evaluating the level of burnout, depression, fatigue, socio-demographic, behavioral and professional characteristics, and quality of life among healthcare professionals. Of the 576 distributed questionnaires among physicians, nurses/technicians and healthcare coworkers, 432 participants returned their questionnaires (75%). All instruments used in our study had been validated and cross-culturally adapted to Serbian language.
Results
The overall prevalence of burnout was 42.4%, with the greatest proportion of burned out in emotional exhaustion domain (66.9%). The multivariable-adjusted model analysis showed that nurses/technicians had a 1.41 times greater chance of experiencing burnout, compared to physicians (OR = 1.41, 95% CI 1.16–7.10), and that with each year of work experience, the chance of burnout increased by about 2% (OR = 1.02, 95% CI 1.00–1.92). Furthermore, it was shown that, with each point in the PHQ-9 score for depression, probability of burnout increased by 14% (OR = 1.14, 95% CI 1.07–1.94). Finally, after controlling all these potential confounders, the Mental Composite Score of SF-36 score showed an independent prognostic value in exploring the burnout presence among HCPs (OR = 1.17, 95% CI 1.03–2.47).
Conclusion
Our research showed a significant level of burnout among healthcare professionals working in oncology, especially among nurses/technicians. The development of effective interventions at both individual and organizational level toward specific risk groups is needed.
: The aim of the study was to evaluate vision-related quality of life (VR-QOL) and treatment satisfaction (TS) in patients with diabetic retinopathy treated with panretinal photocoagulation (PRP).
: ...The panel study included 95 patients who underwent PRP for diabetic retinopathy. Eligible patients with no history of previous PRP were interviewer-administered the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and Retinopathy Treatment Satisfaction Questionnaire (RetTSQ) beforehandand one month after the last session of laser application. The study was conducted between June 2017 and June 2019 at tertiary care center in Serbia, Belgrade. We assessed pre- to post-PRP values of the composite score and subscale scores of VFQ-25 and RetTSQ, using a paired samples
-test. Univariate logistic regression was used to analyze the relationship between binary outcomes and potential predictors. Multivariate regression included predictors from univariate analyses that were statistically significant.
: The mean VFQ-25 composite score was 65.4 ± 17.4 before and 63.3 ± 19.5 after PRP (
= 0.045). Subscale analysis showed that two of the 11 items achieved a significant decrease after laser application (general vision and dependency). The mean RetTSQ score at baseline was 60.0 ± 11.8 and at the exit visit was 60.3 ± 12.3 (
= 0.858). Sub-scale analysis showed significant deterioration for five of the 13 items. Multivariate logistic regression found that significant predictor of VFQ-25 composite score reduction was fewer laser burns (
= 0.002) while significant predictor of RetTSQ total score reduction was presence of hyperlipidaemia (
= 0.021).
: The use of vision-related quality of life and treatment satisfaction questionnaires in conjunction with clinical examination, appears to provide a more comprehensive overview of an individual's daily well-being following PRP. Laser treatment for diabetic retinopathy leads to deterioration of some of the patients' perceived VR-QOL and TS. Health-care providers should inform patients about their treatment options and together decide which therapeutic method is best for them.
Purpose
To translate, culturally adapt and validate the Coronary Revascularisation Outcome Questionnaire (CROQ), a disease-specific tool for measuring health-related quality of life (HRQoL) in ...patients with ischaemic heart disease (IHD), into Serbian language (CROQ-S).
Methods
Validation study was performed at the Clinic for Cardiac Surgery and Clinic for Cardiology, University Clinical Centre of Serbia. We included a convenience sample of 600 patients with IHD divided into four groups. Acceptability, reliability and validity of the CROQ-S were assessed.
Results
CROQ-S was acceptable to patients as demonstrated by less than 1% of missing data for each single item. Cronbach's Alpha was higher than the criterion of 0.70 for all scales in each version except the Cognitive Functioning scale which only met this criterion in the CABG pre-revascularisation version. Mean values of item-total correlations were greater than 0.30 for all scales except the Cognitive Functioning scale in both the pre-revascularisation groups. Compared to the original version, exploratory factor analysis in our study showed more factors; however, the majority of items had a factor loading greater than 0.3 on the right scale. Correlations of CROQ-S scales with the 36-Item Short Form Health Survey and Seattle Angina Questionnaire showed the expected pattern whereby scales measuring similar constructs were most highly correlated.
Conclusion
CROQ-S is an acceptable, reliable and valid disease-specific instrument for measuring HRQoL in this sample of Serbian speaking patients with IHD both before and after coronary revascularisation. However, the Cognitive Functioning scale did not meet all the psychometric criteria and further validation of its responsiveness is required.
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.
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