Vladimir Trkulja

Is quality of life in non-demented Parkinson’s disease patients related to cognitive performance? A clinic-based cross-sectional study

Whilst the association between dementia and poorer health‐related quality of life (Hr‐QoL) in Parkinson’s disease (PD) has been well established, we aimed to explore the relationship between cognitive performance and Hr‐QoL in PD without dementia. Consecutive PD patients (n = 124, 54% men, age 60.4 ± 10.3 years) judged as non‐demented based on DSM‐IV criteria and Mini Mental State Examination, free of other neurodegenerative diseases or psychotic difficulties and antipsychotic/antidepressive/anxyolitic treatment were assessed in a battery of neuropsychological tests. We used Parkinson’s disease questionnaire (PDQ‐39) to asses Hr‐QoL and Beck’s Depression Inventory (BDI) to quantify depression. In the univariate analysis, better performance in each of the tests evaluating visual attention/memory or visuospatial and executive functions was associated with better Hr‐QoL. In multivariate analysis [adjustment for BDI score, PD severity and duration, l‐dopa dose, age, sex, education, employment status and early PD onset (<50 years of age)] in which these tests were either represented by a common variable identified in a principal components analysis or were considered individually, better cognitive performance was independently associated with better Hr‐QoL. The association was conditional on the level of depression, i.e., apparent only in patients with low(er) BDI scores. Cognitive performance appears associated with Hr‐QoL even in non‐demented PD patients.

Oxidative stress parameters in plasma of Huntington's disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects

BackgroundAnimal data and postmortem studies suggest a role of oxidative stress in the Huntingtons disease (HD), but in vivo human studies have been scarce.AimTo assess the presence of oxidative stress in HD patients and its occurrence relative to clinical symptoms.MethodsOxidative stress markers were determined in plasma of HD patients (n = 19), asymptomatic HD gene carriers (with > 38 CAG repeats) (n = 11) and their respective sex and agematched healthy controls (n = 47 and n = 22) in a cross-sectional study.ResultsWith adjustment for age and sex, HD patients had higher plasma lipid peroxidation (LP) levels (ratio 1.20, 95% CI 1.09 to 1.32, p < 0.001) and lower reduced glutathione (GSH) levels (ratio 0.72, CI 0.55 to 0.94, p = 0.011) than their age and sex-matched controls. Although considerably younger, HD gene carriers did not differ from HD patients regarding LP and GSH levels, and had higher plasma LP (ratio 1.16, CI 1.02 to 1.32, p = 0.016) and lower GSH than their matched controls (ratio 0.73, CI 0.5 to 1.05). They had higher LP (ratio 1.18, CI 1.02 to 1.34, p = 0.019) and lower GSH (ratio 0.75, CI 0.51 to 1.11) than the healthy subjects matched to HD patients.ConclusionsOxidative stress is more pronounced in HD patients and asymptomatic HD gene carriers than in healthy subjects. Differences in plasma LP and GSH are in line with the brain findings in animal models of HD. Data suggest that oxidative stress occurs before the onset of the HD symptoms.

Higher mean platelet volume determined shortly after the symptom onset in acute ischemic stroke patients is associated with a larger infarct volume on CT brain scans and with worse clinical outcome

OBJECTIVE Mean platelet volume (MPV) determined shortly after the onset of acute ischemic stroke represents the pre-stroke values. Data on its relationship to stroke severity/outcome have been conflicting. We related MPV to infarct volume on CT brain scans and risk of death/dependence 7 days and 3 months post-stroke. METHODS MPV (within 30h since stroke onset), infarct volume (13-83h since stroke onset) and clinical outcomes were evaluated in 81 consecutive patients (32 men, age 52-91 years, 10 small artery occlusion, 10 large artery atherosclerosis, 29 cardioembolic, 32 multiple probable/possible etiology). RESULTS Higher MPV was independently associated with larger ln-infarct volume [estimate 0.259, 95% confidence interval (CI) 0.004-0.513, P=0.046], greater risk of death/dependence 7 days post-stroke [relative risk (RR)=1.077, 95% CI 1.005-1.115, P=0.036], and greater risk of death/dependence 3 months post-stroke (RR=1.077, 95% CI 1.001-1.158, P=0.048). Considered covariates: stroke etiology, CT scan timing, platelet count and other hematological parameters, demographic variables, history of cerebrovascular, cardiac or cardiovascular diseases, diabetes, serum chemistry, previous antiplatelet and statin use and treatments delivered after the index event. CONCLUSIONS Data support the view about MPV as a determinant of severity/outcome of the acute ischemic stroke.

Association of rural life setting and poorer quality of life in Parkinson's disease patients: a cross-sectional study in Croatia

Assessment of quality of life (QoL) has become an important measure in Parkinsons disease (PD) healthcare as a part of the efforts to evaluate the ‘total burden’ of the illness, and not only the motor disabilities. By analogy with some other diseases, we aimed to investigate potential urban–rural disparities in QoL in PD patients. A total of 111 consecutive PD patients were assessed for QoL using a specific 39‐item version of PD quality of life questionnaire (PDQ‐39) in a cross‐sectional study involving two centers in Croatia. Rural life setting (adjustment for center, age, sex, levodopa dose, disease duration and severity, education, employment status and number of household co‐members) was an independent negative predictor of QoL: rural patients had significantly (P < 0.05) worse PDQ‐39 Summary Index Score and most of the PDQ‐39 subscale scores (cognition, social support, stigma, emotional wellbeing and mobility score, and communication and activity of daily living scores with borderline significance) than their urban counterparts. Socioeconomic background should be considered in attempts to achieve the best management of PD patients’ needs.

Single incision versus standard multiport laparoscopic cholecystectomy: Up-dated systematic review and meta-analysis of randomized trials

BACKGROUND AND PURPOSE We aimed to compare single incision laparoscopic cholecystectomy (SILC) to the standard multiport technique (MLC) for clinically relevant outcomes in adults. METHODS Systematic review and random-effects meta-analysis of randomized trials. RESULTS We identified 30 trials (SILC N = 1209, MLC N = 1202) mostly of moderate to low quality. Operating time (30 trials): longer with SILC (WMD = 12.4 min, 95% CI 9.3, 15.5; p < 0.001), but difference reduced with experience - in 10 large trials (1321 patients) WMD = 5.9 (-1.3, 13.1; p = 0.105). Intra-operative blood loss (12 trials, 1201 patients): greater with SILC, but difference practically irrelevant (WMD = 1.29 mL, 0.24-2.35; p = 0.017). Procedure failure (27 trials, 2277 patients): more common with SILC (OR = 13.9, 4.34-44.7; p < 0.001), but overall infrequent (SILC pooled incidence 4.39%) and almost exclusively addition of a trocar. Post-operative pain (29 trials) and hospital stay (22 trials): no difference. Complications (30 trials): infrequent (SILC pooled incidence 5.35%) with no overall SILC vs. MLC difference. Incisional hernia (19 trials, 1676 patients): very rare (15 vs. 4 cases), but odds significantly higher with SILC (OR = 4.94, 1.26-19.4; p = 0.025). Cosmetic satisfaction (16 trials, 11 with data at 1-3 months): in 5 trials with non-blinded patients (N = 513) in favour of SILC (SMD = 1.83, 0.13, 3.52; p = 0.037), but in 6 trials with blinded patients (N = 719) difference small and insignificant (SMD = 0.42, -1.12, 1.96; p = 0.548). DISCUSSION SILC outcomes largely depend on surgeons skill, but regardless of it, when compared to MLC, SILC requires somewhat longer operating time, risk of incisional hernia is higher (but overall very low) and early cosmetic benefit is modest. CONCLUSION From the (in)convenience and safety standpoint, SILC is an acceptable alternative to MLC with a modest cosmetic benefit.

On-admission serum uric acid predicts outcomes after acute myocardial infarction: systematic review and meta-analysis of prognostic studies

Aim To evaluate the prognostic value of serum uric acid (SUA) in acute myocardial infarction (AMI) patients. Methods Systematic review and random-effects meta-analysis of prognostic studies assessing AMI outcomes (death, major adverse cardiac events, MACE) in relation to on-admission SUA. Results Nine studies (7655 patients) were identified, 6 in the ST-segment elevation AMI patients treated with invasive revascularization and three in mixed AMI type cohorts with variable reperfusion strategies. “High” SUA (vs “low,” different cut-offs) was univariately associated with higher short-term mortality (8 studies/6805 patients; odds ratio [OR], 3.24; 95% confidence interval [CI], 2.47-4.27) and incidence of MACE (7/6467; OR, 2.46; 95% CI, 1.84-3.27, moderate heterogeneity, mild bias), and with higher medium-term mortality (5/5194; OR, 2.69; 95% CI, 2.00-3.62, moderate heterogeneity, mild bias) and MACE (4/4299; OR, 1.93; 95% CI, 1.36-2.74, high heterogeneity, mild bias). It was independently associated with a higher short-term (4/3625; OR, 2.26, 95% CI, 1.85-2.77) and medium/long-term (3/2683; hazard ratio [HR], 1.30; 95% CI 1.01-1.68, moderate heterogeneity, mild bias) occurrence of poor outcomes (death/MACE). As a continuous variable (by 50 μmol/L), higher SUA was also independently associated with poorer medium/long-term outcomes (4/3533; HR, 1.19; 95% CI, 1.03-1.37, high heterogeneity, mild bias). All individual study effects (unadjusted or adjusted) were in the same direction, but differed in size. Heterogeneity was mainly due to the included AMI type and/or definition of MACE. All bias-corrected pooled effects remained significant. Conclusion Based on the available data, high(er) on-admission SUA independently predicts worse short-term and medium/long-term outcomes after AMI. However, the number of data are modest and additional prospective studies are warranted.

Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease

AIM Novel effective treatment is urgently needed for sporadic Alzheimers disease (sAD). M30 ([5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]) and HLA-20 (5-{4-propargylpiperazin-1-ylmethyl}-8-hydroxyquinoline) are brain permeable, iron chelating compounds with antioxidant activity, showing also neuroprotective activity in animal models of neurodegeneration.Weaimed to explore their therapeutic potential in non-transgenic (non-Tg) rat model of sAD developed by intracerebroventricular administration of streptozotocin (STZ-icv). MAIN METHODS Therapeutic effects of chronic oral M30 (2 and 10 mg/kg) and HLA20 (5 and 10 mg/kg) treatment on cognitive impairment in STZ-icv rat model were explored by Morris Water Maze (MWM) and Passive Avoidance (PA) tests in neuropreventive and neurorescue paradigms. Data were analysed by Kruskal–Wallis and Mann–Whitney U test (p b 0.05). KEY FINDINGS Five-day oral pre-treatment with M30 and HLA20 dose-dependently prevented development of spatial memory impairment (MWM probe trial-time +116%/M30; +60%/HLA20) in STZ-icv rat model (p b 0.05). Eleven-week oral treatment with M30 (3×/week), initiated 8 days after STZ-icv administration dosedependently ameliorated already developed cognitive deficits in MWM test (reduced number of mistakes 3 months after the STZ-icv treatment — 59%; p b 0.05) and fully restored them in PA test (+314%; p b 0.05). Chronic M30 treatment fully restored (−47%/PHF1;−65%/AT8; p b 0.05) STZ-induced hyperphosphorylation of tau protein and normalized decreased expression of insulin degrading enzyme (+37%; p b 0.05) in hippocampus. SIGNIFICANCE The results provide first evidence of therapeutic potential of M30 and HLA20 in STZ-icv rat model of sAD with underlying molecular mechanism, further supporting the important role of multi-target ironchelators in sAD treatment.

Restless Legs Syndrome in Hemodialysis Patients: Association with Calcium Antagonists

Uremia-related restless legs syndrome (RLS) is a known form of secondary RLS. This cross-sectional survey included patients (n = 82) on stable hemodialysis (HD; >3 months, Kt/V >1.2) who were iron-replete, free of neurodegenerative or psychiatric disorders, severe polyneuropathy and radiculopathy, not exposed to antipsychotics/antidepressants, and not severely anemic. Forty-nine (60%) were RLS ‘positive’, and 25 (31%) had severe/very severe symptoms (International Restless Legs Syndrome Study Group criteria). None had been diagnosed previously. In a multivariate analysis, the prevalence of RLS was higher in diabetic patients [vs. nondiabetics; prevalence ratio (PR) 2.32, 95% CI 1.50–3.60, p < 0.001] and those exposed to Ca2+ antagonists (vs. nonexposed; PR 2.02, CI 1.47–2.76, p < 0.001), and also increased with dialysis duration (PR 1.05, 95% CI 1.02–1.09, p < 0.001). Association of Ca2+ antagonists and RLS in uremic patients has not been reported previously and deserves further research.

Higher Serum Triglyceride Level in Patients with Acute Ischemic Stroke Is Associated with Lower Infarct Volume on CT Brain Scans

We investigated the relationship between serum triglyceride level and acute ischemic stroke severity using infarct volume on CT brain scans as a marker. A total of 121 consecutive acute ischemic stroke patients (53 males and 68 females, age 47–93 years) with anterior circulation (75%), posterior circulation (9%) or lacunar infarcts (16%) were examined. All patients were admitted within 24 h of the symptom onset, and CT scans were taken over the subsequent 24–72 h. With adjustment for the infarct type, age, sex, timing of CT imaging (24–36, >36–48 or >48–72 h since admission), atrial fibrillation, hypertension, fasting cholesterol and glucose levels, a higher (≧1.70 mmol/l) fasting serum triglyceride level (within 24 h after admission) was associated with a lower infarct volume (p = 0.014). In line with a recent report on milder clinical symptoms in acute ischemic stroke patients with higher triglycerides, the results suggest an independent association between serum triglyceride level and stroke severity.

Nondemented Parkinson disease patients : is cognitive performance associated with depressive difficulties?

BackgroundPoorer cognitive performance in depressed versus nondepressed nondemented Parkinson disease (PD) patients has been suggested. ObjectiveInvestigate the relationship between level of depression assessed on a depression-measuring scale and cognitive performance in nondemented PD patients. MethodsNondemented idiopathic PD patients (n=110) were evaluated for the level of depression [cognitive-affective items of the Becks Depression Inventory (BDI)] and performance in a set of tests evaluating cognitive domains typically affected in PD (memory, visuospatial, and executive functions). ResultsMultiple regression analysis of BDI scores demonstrated independent association of poorer cognitive performance, more severe parkinsonism, and poorer education with higher BDI scores. The association between poorer cognition and higher BDI scores was conditional on education, that is, was apparent only in less educated patients (<12 y of formal education). ConclusionsPoorer cognitive performance in nondemented idiopathic PD patients is associated with more severe depressive difficulties. Poorer education is also associated with more severe depression. Education modifies the cognition-depression relationship.