Evaluation of the self-assessment knowledge regarding cardiopulmonary resuscitation in medical students at the University of Belgrade.

OBJECTIVE: Cardiopulmonary resuscitation (CPR) is a vital skill that can improve the outcome of patients with sudden cardiac arrest. To raise awareness about CPR some countries have introduced an obligatory First Aid Course (FAC), usually done parallelly to a driver's license (DL). While expected of doctors to know CPR, the curriculum of some medical schools does not seem to have enforced measures to improve that knowledge. The aim was to have students self-evaluate their current knowledge of CPR, comparing it before university and whether it improved during their studies. SUBJECTS AND METHODS: A cross-sectional study was conducted in October 2020 using an anonymous questionnaire among students at the Faculty of Medicine in Belgrade (studies in English). RESULTS: A total of 172 (66.7%) students possessed a DL, of which 39.8% felt they were ready, 45.8% felt neutral, and 14.4% felt unable to perform CPR. The total number of students that completed a FAC during their studies was 165. Analysis was performed on the ability assessment data after the first FAC during studies, comparing it to FAC for DL and assessments at the end of studies. No statistically significant difference was observed in the level of self-reported ability to perform CPR, while a statistically significant difference was found in ability assessments when comparing only the FAC for the DL, and the one after the first FAC during medical studies, with students feeling more prepared after the FAC for DL. Across the sample, 90.2% of the students wished they had more CPR training during their medical studies. CONCLUSIONS: From this study, it may conclude that students wish and need more CPR training in their curriculum.

GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

Extensive myelitis after oral polio vaccination: MRI features.

A 7-year-old boy presented with fever and ataxia 20 days after oral polio vaccination. Magnetic resonance imaging showed extensive myelitis, involving both anterior and posterior horns of the gray matter. Complete posttreatment recovery was evident. Postvaccinal myelitis after oral polio vaccination, of either infectious or immune mediated etiology, is very rare entity that should be promptly recognized in order to initiate adequate treatment.

A phase Ib dose-escalation study of everolimus combined with cisplatin and etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer.

BACKGROUND: This phase Ib study aimed to establish the feasible everolimus dose given with standard-dose etoposide plus cisplatin (EP) for extensive-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: An adaptive Bayesian dose-escalation model and investigator opinion were used to identify feasible daily or weekly everolimus doses given with EP in adults with treatment-naive extensive-stage SCLC. A protocol amendment mandated prophylactic granulocyte colony-stimulating factor (G-CSF). Primary end point was cycle 1 dose-limiting toxicity (DLT) rate. Secondary end points included safety, relative EP dose intensity, pharmacokinetics, and tumor response. RESULTS: Patients received everolimus 2.5 or 5 mg/day without G-CSF (n=10; cohort A), 20 or 30 mg/week without G-CSF (n=18; cohort B), or 2.5 or 5 mg/day with G-CSF (n=12; cohort C); all received EP. Cycle 1 DLT rates were 50.0%, 22.2%, and 16.7% in cohorts A, B, and C, respectively. Cycle 1 DLTs were neutropenia (cohorts A and B), febrile neutropenia (all cohorts), and thrombocytopenia (cohorts A and C). The most common grade 3/4 adverse events were hematologic. Best overall response was partial response (40.0%, 61.1%, and 58.3% in cohorts A, B, and C, respectively). CONCLUSIONS: Everolimus 2.5 mg/day plus G-CSF was the only feasible dose given with standard-dose EP in untreated extensive-stage SCLC.

Psychosis following stab brain injury by a billiard stick.

Traumatic brain injury sometimes can lead to psychotic disorder which resembles schizophrenia. We report a 17-year-old boy, admitted to psychiatric department for psychotic symptomatology. He had suffered penetrating craniocerebral injury after stabbing by a billiard stick, three years earlier. On admission, he expressed delusions with paranoid and religious content. The magnetic resonance imaging of the brain showed a 10 cm large tubular area of posttraumatic encephalomalacia of the left hemisphere, whereas the electroencephalography revealed slow left temporal activity. The patient's recovery was uneventful with clozapine at a dosage of 100 mg daily. This case shows the diagnostic challenge in differentiation between schizophrenia and psychotic disorder due to traumatic brain injury. The authors emphasise the importance of imaging of the brain, especially magnetic resonance, in establishing the diagnosis of psychotic disorder due to traumatic brain injury.

Determinants of brain iron in multiple sclerosis: a quantitative 3T MRI study.

OBJECTIVES: Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to indicate brain iron accumulation in a quantitative manner. We used this technique to assess brain iron levels in different stages of MS and healthy controls (HC) and determined their relation with demographic, clinical, neuropsychological, and other imaging variables. METHODS: We studied 113 consecutive patients (35 clinically isolated syndrome [CIS], 78 MS) and 35 HC with 3 T MRI and clinical and neuropsychological examination. Iron deposition in subcortical gray matter structures was assessed by automated, regional calculation of R2* rates. RESULTS: Basal ganglia (BG) R2* levels were significantly increased in MS compared to CIS (p < 0.001) and HC (p < 0.005). They were correlated with age (r = 0.5, p < 0.001), disease duration (r = 0.5, p < 0.001), Expanded Disability Status Scale (r = 0.3, p < 0.005), and the z values of mental processing speed (r = -0.3, p < 0.01). Stepwise linear regression analysis revealed gray matter atrophy as the strongest independent predictor of BG R2* levels (p < 0.001), followed by age (p < 0.001) and T2 lesion load (p < 0.005). CONCLUSION: BG iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, which argues for iron deposition as an epiphenomenon. The absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS.

Reorganization in cognitive networks with progression of multiple sclerosis: insights from fMRI.

OBJECTIVES: Cognitive dysfunction (CD) is frequent in multiple sclerosis (MS) and can occur at early stages. Whereas functional reorganization with disease progression has been described for the motor system in MS using fMRI, no such studies exist for cognition. We attempted to assess the concept of functional reorganization concerning cognition using a simple "Go/No-go" fMRI paradigm. METHODS: Patients with a clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS) (n = 10), or secondary progressive MS (SPMS) (n = 10), and 28 healthy controls (HC), underwent a comprehensive neuropsychological test battery, clinical examination, structural imaging, and an fMRI Go/No-go discrimination task at 3 T. RESULTS: Patients performed worse than HC regarding memory, sustained attention and concentration, and information processing. These differences were driven by patients with SPMS. The fMRI task elicited activation in a widespread network including bilateral mesial and dorsolateral frontal, parietal, insular, basal ganglia, and cerebellar regions. Task performance was similar between phenotypes, but deviation from the activation pattern observed in HC and patients with CIS increased with disease progression. Patients with RRMS showed increased brain activation in the precuneus, both superior parietal lobes, and the right fusiform gyrus, and recruited the hippocampus with increasing demands. Patients with SPMS demonstrated the most abnormal network function, including recruitment of pre-SMA, bilateral superior and inferior parietal, dorsolateral prefrontal, right precentral, bilateral postcentral, and right temporal brain areas. CONCLUSION: Using a cognitive fMRI paradigm, we were able to confirm adaptive changes of neuronal activation with progressing MS and to provide strong evidence for their compensatory nature, at least partially.

Cognitive impairment in relation to MRI metrics in patients with clinically isolated syndrome.

BACKGROUND: Cognitive deficits are frequent in multiple sclerosis (MS) and have been associated with morphologic brain changes. Less information exists on their extent and relation to MRI findings in clinically isolated syndrome (CIS). It is also unclear if structural changes as detected by magnetization transfer (MT) imaging may provide an additional explanation for cognitive dysfunction. OBJECTIVE: To analyse the extent of cognitive deficits and their relation to MRI metrics including MT imaging in CIS compared to relapsing-remitting MS (RRMS). METHODS: Forty-four CIS and 80 RRMS patients underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) and a 3 T MRI scan. RESULTS: BRB-N subtests revealed similar results in CIS and RRMS. Impaired mental processing speed was most prevalent in both groups (CIS 13.6%; RRMS 16.3%) and thus served for correlation with MRI metrics. Using stepwise linear regression analyses, the strongest predictor for decreased mental processing speed was normalized cortex volume (p < 0.001) followed by T2-lesion load (p < 0.05) in RRMS, whereas cortical MT ratio was the only MRI parameter associated with decreased mental processing speed in CIS (p < 0.005). CONCLUSION: Cognitive dysfunction occurs in CIS in a pattern similar to RRMS, with impaired mental processing speed being most prevalent. Cortical MT-ratio changes may be an early sign for tissue changes related to impaired mental processing speed in CIS while this association shifts to increased signs of cortical atrophy and lesion load in RRMS.

Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

BACKGROUND: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. OBJECTIVES: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. METHODS: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. RESULTS: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. CONCLUSIONS: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Lesion probability mapping to explain clinical deficits and cognitive performance in multiple sclerosis.

BACKGROUND: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and disability is only modest, however. Strategic lesion location might at least partially account for this 'clinico-radiologic paradox'. OBJECTIVES: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing-remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions. RESULTS: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location. CONCLUSIONS: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent.

[Low dose CT protocol--capability for early detection of lung carcinoma].

Lung carcinoma is the most common cause of death among men who died from cancer; also, among women, the incidence of this disease is on the increase. Use of multislice computed tomography (MSCT) has enhanced detection capability for pulmonary nodules. Nowadays, low radiation dose CT technique (LDCT) increases interest in lung cancer screening. This study is a part of the project whose aim is early diagnosis and well-timed treatment of lung carcinoma. Participants in this screening were above the age of 40, both smokers and non-smokers, who have undergone MSCT examination of lungs following low-dose protocol (LDCT). In the first ten months of the study, 375 volunteers have been examined. Overall number of detected nodules was 361; and 303 of these nodules have been characterized as non-calcificated. 95 participants (24.27%) had at least one non-calcificated nodule. 17 patients were referred to pulmologist and for further clinical evaluation. LDCT significantly increases detection of small, non-calcificated pulmonary nodules, and, therefore, gives higher opportunity to detect early lung carcinoma.

Brain activation patterns elicited by the 'Faces Symbol Test' -- a pilot fMRI study.

The Faces Symbol Test (FST) has recently been proposed as a brief and patient-friendly screening instrument for the assessment of cognitive dysfunction in patients with multiple sclerosis (MS). However, in contrast to well-established MS screening tests such as the Paced Auditory Serial Addition Test, the neural correlates of the FST have not been investigated so far. In the present study, we developed a functional MRI (fMRI) version of the FST to provide first data on brain regions and networks involved in this test. A sample of 19 healthy participants completed a version of the FST adapted for fMRI, requiring matching of faces and symbols in a multiple choice test and two further experimental conditions drawing on cognitive subcomponents (face matching and symbol matching). Imaging data showed a differential involvement of a fronto-parieto-occipital network in the three conditions. The most demanding FST condition elicited brain activation patterns related with sustained attention and executive control. These results suggest that the FST recruits brain networks critical for higher-order cognitive functions often impaired in MS patients.

Genotypic and phenotypic resistance testing of HIV-1 in routine clinical care.

Data on genotypic and phenotypic resistance testing of HIV-1 in the routine clinical setting are lacking. In a retrospective single-center study, all patients (n = 102) for whom genotypic resistance typing (GRT) and phenotypic resistance typing (PRT) were performed during the calendar year 2002 were examined. GRT and PRT results were concordant for 79% of the drugs, being highest for nevirapine (92%) and lowest for didanosine (57%). Concordance of results for protease inhibitors was lowest for lopinavir (78%) and highest for indinavir (88%). Discordant results for lamivudine were observed in 16% of patients; 90% of these results corresponded to high-level resistance by PRT and susceptibility by GRT. Overall, HIV loads were lower and CD4+ cell counts higher after therapy following resistance testing, but a significant association with the number of active drugs as predicted by GRT or PRT could not be identified. In a subgroup of 43 patients with virological failure under antiretroviral therapy and sufficient follow-up data, HIV loads were significantly lower after 3 and 6 months. More patients with HIV loads <400/ml had 2 or more active drugs according to PRT (21/29 [75%]) than according to GRT ([15/29 [52%]; p = 0.109. This was also found for HIV loads <50/ml (PRT 16/22 [72%], GRT 10/22 [42%]; p = 0.103), although the differences were not statistically significant. There was no discernable difference between GRT and PRT in the clinic-based population, but the numbers of resistance tests performed are not sufficient to draw definitive conclusions.

Influence of age, gender, education and dexterity on upper limb motor performance in Parkinsonian patients and healthy controls.

Finger tapping, the most widely used test for evaluating motor dysfunction in Parkinson's disease (PD), was found to react sensitively to disease specific factors like disease severity and changes in medication. A possible interference caused by disease unrelated demographic factors--age, gender, education and dexterity--however has not yet been studied systematically. Various components of tapping performance of 187 healthy subjects and 200 PD patients were assessed by means of the BRAIN TEST, a digitalized test battery. The effects of demographic factors--above all education and age--were found to be significant. These influences generally affect different aspects of movement to a different extent, with speed and akinesia being affected more severely than dysmetria and arrhythmokinesis. Our study suggests that whenever precise assement of upper limb motor performance is needed, specific corrections for these demographic factors in both healthy controls and PD patients are necessary.