University of Zagreb Medical School Repository

University of Zagreb Medical School Repository
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    2851 research outputs found

    The association between clinical and laboratory findings of bullous pemphigoid and dipeptidyl peptidase-4 inhibitors in the elderly: a retrospective study

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    Aim: To evaluate the association between the use of dipeptidyl peptidase-4 inhibitors (DPP4I) and clinical and laboratory findings of bullous pemphigoid (BP) in patients treated at the European Reference Network - Skin Reference Centre in Croatia. ----- Methods: This retrospective study enrolled 82 patients treated for BP at the Department of Dermatovenereology, University Hospital Center Zagreb from January 2015 to December 2019. Clinical features of BP, presence of comorbidities, and laboratory findings of anti-BP antibodies and eosinophilia were analyzed in three groups of BP patients: 1) diabetes mellitus (DM) type II patients treated with DPP4I, 2) DM type II patients not treated with DPP4I, and 3) non-DM type II patients. ----- Results: The average age and anti-BP180 titer were similar in all three groups. DPP4I group had a slightly lower eosinophil level in both peripheral blood (4.89%) and biopsy specimens (87.5%), but the difference was not significant. The prevalence of inflammatory BP in DPP4I group was 76.5%. DPP4I group had significantly higher percentage of patients with chronic renal failure and dementia (52.9% and 11.8%, respectively) compared with non-DPP4I DM (14.3% and 0%, respectively) and non-DM type II patients (15.7% and 0%, respectively). ----- Conclusion: BP patients treated with DPP4I and those not treated with DPP4Is did not significantly differ in laboratory findings. However, DPP4I treatment was associated with an inflammatory subtype of BP and a higher prevalence of dementia and chronic renal failure. These findings warrant further research into the association of BP and DM with dementia and chronic renal failure

    How to face the aging world – lessons from dementia research

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    A continuous rise in life expectancy has led to an increase in the number of senior citizens, now amounting to a fifth of the global population, and to a dramatic increase in the prevalence of diseases of the elderly. This review discusses the threat of dementia, a disease that imposes enormous financial burden on health systems and warrants efficient therapeutic solutions. What we learned from numerous failed clinical trials is that we have to immediately take into account two major elements: early detection of dementia, much before the onset of symptoms, and personalized (precision) medicine treatment approach. We also discuss some of the most promising therapeutic directions, including stem cells, exosomes, electromagnetic fields, and ozone

    Anatomska podjela subtalamičke jezgre [Anatomical subdivison of the subthalamic nucleus]

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    Subthalamic nucleus is one of the most interesting structures of basal ganglia. Neurosurgical stimulation of STN has improved condition of many patients with levodopa resistant Parkinson’s disease. However, it also led to many unwanted side-effects due to the inconclusive delineation of STN segments’ borders. Previous studies which dealt with this topic did not produce definite answer about number and location of STN segments. In this study we analyzed the distribution of five neuronal markers in the STN: NeuN, calretinin, calbindin, parvalbumin and nNOS. All markers were positive in STN except calbindin. The largest population of neurons in STN is positive for nNOS, and the smallest population is calretinin positive. By analyzing the spatial distribution of neurons in STN we could not determine the borders between segments nor any individual segments in STN. Furthermore, we analyzed 1,5 and 3T MR images to determine STN segments. We were not able to determine any segments on these images. However, we analyzed the precision of DBS electrode location in the STN and based on these data we created “virtual” motor segment of STN. The stimulation within these “virtual segment” provided satisfactory clinical results in controlling symptoms of Parkinson’s disease

    The influence of therapeutic hypothermia on the outcomes of cardiac arrest survivors: a retrospective cohort study

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    Aim: To determine whether therapeutic hypothermia (TH) improves survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. ----- Methods: This retrospective cohort study enrolled patients treated for OHCA with a return of spontaneous circulation admitted to the Cardiac Intensive Care Unit from October 2000 until March 2019. Data were collected from medical archives. Propensity score matching was used. The primary endpoint was death during hospital stay and secondary endpoint was cerebral performance category (CPC) score at discharge. ----- Results: Out of 152 patients included in the study, 58 (38.7%) underwent TH treatment. After matching (which left 70 patients in the analysis), death during hospital stay occurred less often in TH group (28.6% vs 57.1%, P=0.029), while the difference in CPC score was not significant. Cox proportional hazards model showed the predictors of death during hospital stay to be TH (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.13-0.68, P=0.004), initial Glasgow Coma Scale score of 3 (HR 7.55, 95% CI 1.44-39.63, P=0.017), and heart failure (HR 2.35, 95% CI 1.02-5.34, P=0.045). TH was not an independent predictor of CPC score. Mann-Whitney U test and linear regression model showed that TH was associated with higher gain in GCS. ----- Conclusion: TH was associated with better survival and certain variables suggesting improved neurological outcomes, suggesting that TH is a vital treatment option for comatose OHCA survivors

    Role of platelet gene polymorphisms in ischemic pediatric stroke subtypes: a case-control study

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    Aim: To assess the role of human platelet antigens (HPA), P-selectin gene (SELP) polymorphisms, and HPA and SELP haplotypes with factor V (FV) R506Q in ischemic pediatric stroke (IPS) subtypes: cerebral sinovenous thrombosis (CSVT), perinatal (PAIS), and childhood (CAIS) arterial ischemic stroke. ----- Methods: This case-control study enrolled 150 children with confirmed IPS and 150 age- and sex-matched controls. FV R506Q and HPA-1 were genotyped with CVD StripAssay®, HPA-2 and HPA-3 with real-time polymerase chain reaction, SELP S290N, V599L, and T715P with high resolution melting analysis, and SELP N562D with sequence-specific polymerase chain reaction. ----- Results: HPA-1b allele (odds ratio [OR] 2.75, 95% confidence interval [CI] 1.02-7.42, P=0.048) and HPA-1a2a3b (OR 5.46, 95% CI 1.51-19.76, P=0.011), HPA-1b2a3a (OR 7.00, 95% CI 1.25-39.13, P=0.028), and HPA-1b2b3a (OR 11.39, 95% CI 1.39-92.95, P=0.024) haplotypes increased the risk for CSVT. HPA-3b allele was significantly associated with 2-fold lower risk for PAIS (OR 0.49, 95% CI 0.26-0.89, P=0.020) and CAIS (OR 0.47, 95% CI 0.26-0.86, P=0.014) and non-significantly associated with increased risk for CSVT (OR 6.43, 95% CI 0.83-50.00, P=0.022). HPA-1a2b3a haplotype was significantly associated with CAIS (OR 6.76, 95% CI 2.13-21.44, P=0.001). The inclusion of FV R506Q in SELP haplotype analysis increased the risk for PAIS 4-fold in QNDVT carriers (OR 8.14, 95% CI 0.93-71.33, P=0.060) compared with NDVT haplotype (OR 2.45, 95% CI 0.98-6.18, P=0.058), but the result was not significant. ----- Conclusion: Individual HPAs, and particularly HPA haplotypes, are involved in IPS subtypes pathogenesis. A possible risk-inducing synergistic effect of SELP haplotypes with FV R506Q is restricted to PAIS only

    Safety and efficacy of nivolumab as a second line therapy in metastatic renal cell carcinoma: a retrospective chart review

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    Aim To assess diseases outcomes and tolerability of real-life second-line nivolumab in a series of metastatic renal cell carcinoma (mRCC) patients. ----- Methods This retrospective chart review involved prospectively monitored patients (named patient program) treated with second-line nivolumab for mRCC at the University Hospital Centre Zagreb from February 2016 to March 2018. ----- Results The study enrolled 30 patients, 5 of whom (16.7%) had a complete response. The mean ± standard deviation therapeutic response time to nivolumab treatment was 14.07 ± 8.92 months, with a minimum treatment duration of 2 months and a maximum of 24 months. The median duration of therapy was 17 months (mean: 15.8 months; range: 3-24 months), and 50% (n = 15/30) of patients remained alive at the end of follow up. The most common adverse events associated with nivolumab were fatigue (26.67%; n = 8/30), anemia (10.0%; n = 3/30), adrenal insufficiency (6.67%; n = 2/30: G1 = 1, G2 = 1), grade 2 pneumonitis (6.67%; n = 2/30), grade 2 neuropathy (6.67%; n = 2/30), rash (6.67%; n = 2/30: G1 = 1, G2 = 1), and hepatitis (3.33%; n = 1/30). ----- Conclusion The present study indicates acceptable patient responses and tolerability of nivolumab in mRCC

    Utjecaj stresne hiperglikemije na bolnički ishod akutne egzacerbacije kronične opstruktivne plućne bolesti [Impact of stress hyperglycemia on hospital outcome of acute exacerbation of chronic oobstructive pulmonary disease]

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    Impact of stress hyperglycemia on outcomes from acute exacerbations of COPD (AECOPD) has not been established. The aim of the research is to determine the impact of stress hyperglycemia (blood glucose > 6,9 and 7,8 mmol/L postprandial) on intrahospital mortality, length of hospitalization and specific clinical parameters. We enrolled 272 non-diabetics hospitalized in General Hospital Zabok for AECOPD in one year period and divide them in 2 groups according to glucose levels in venous plasma at admission. After corticosteroid therapy each group was further stratified according to glycemia after 24 hours and before discharge. Beside main aims, we evaluated impact on lung function changes, CRP level, sputum culture, the presence of radiological pneumonia and need for mechanical ventilation. Results showed that 113 patients (41,5%) had stress hyperglycemia at admission and statistically significant higher average glucose levels (9,7 vs 5,7 mmol/l). Fatal outcome happened in 8,1 % cases and it was three times more often between patients with stress hyperglycemia (13,3 % vs 4,4%), independent of age, sex, FEV1 and COPD severity or duration . The relative risk (RR) of death or long inpatient stay was significantly increased in patients with stress hyperglycemia. For each 1 mmol/L increase in blood glucose the absolute risk of adverse outcome increased by 1,23 (95% CI. 1,04 to 1,46, p =0,015). Glucose levels at admission were much higher in non-survivors than survivors (9,65 vs 6,35 mmol/L). Length of hospital stay was longer in patients with stress hyperglycemia (9 vs 7 days, p= 0,001), so was the incidence of pneumonia (29,2% vs 10,1%, p<0,001). In patients with steroid hyperglycemia, glucose levels significantly increased (5,2 vs 8 mmol/L), but without significant correlation to mortality or number of hospital days. Stress hyperglycemia in non-diabetic patients with acute exacerbation of COPD is negative prognostic factor of intra-hospital outcome. This research acquired new knowledge about impact of stress hyperglycemia on outcome of AECOPD and hopefully will stimulate further studies about stricter glycemic control that could possibly contribute to a better treatment outcome of these patients

    Use of pharmacogenomics in elderly patients treated for cardiovascular diseases

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    Older people are increasingly susceptible to adverse drug reactions (ADRs) or therapeutic failure. This could be mediated by considerable polypharmacy, which increases the possibility of drug-drug and drug-gene interactions. Precision medicine, based on individual genetic variations, enables the screening of patients at risk for ADRs and the implementation of personalized treatment regimens. It combines genetic and genomic data with environmental and clinical factors in order to tailor prevention and disease-management strategies, including pharmacotherapy. The identification of genetic factors that influence drug absorption, distribution, metabolism, excretion, and action at the drug target level allows individualized therapy. Positive pharmacogenomic findings have been reported for the majority of cardiovascular drugs (CVD), suggesting that pre-emptive testing can improve efficacy and minimize the toxicity risk. Gene variants related to drug metabolism and transport variability or pharmacodynamics of major CVD have been translated into dosing recommendations. Pharmacogenetics consortia have issued guidelines for oral anticoagulants, antiplatelet agents, statins, and some beta-blockers. Since the majority of pharmacogenetics recommendations are based on the assessment of single drug-gene interactions, it is imperative to develop tools for the prediction of multiple drug-drug-gene interactions, which are common in the elderly with comorbidity. The availability of genomic testing has grown, but its clinical application is still insufficient

    Povezanost kliničkih, laboratorijskih i termografskih nalaza u bolesnika s ulceroznim kolitisom [Association between clinical, laboratory and thermographic findings in patients with ulcerative colitis]

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    INTRODUCTION: The aim of this paper was to describe the diagnostic potential of thermography in surveillance and as a noninvasive biomarker of disease activity in patients with extensive ulcerative colitis. MATERIAL AND METHODS: 30 patients with active extensive colitis and 30 healthy subjects where enrolled in the study. Patients where prospectively followed and treated for 6 months. All of the participants where subject to infrared thermography at enrollment but UC patients were screened once more after 6 months. Thermographic criteria (Tsred ROI 1 – 4) where compared among the two groups of participants but also compared to standard clinical, laboratory and endoscopic markers of disease activity. RESULTS: higher temperatures were observed among patients with active ulcerative colitis compared to healthy subjects as well as in patients with active disease compared to those in remission after 6 months. Statistically significant correlation was observed between average abdominal temperatures and clinical (Mayo score), laboratory (FC, CRP) and endoscopic findings (Mayo ESS) in patients with ulcerative colitis. CONCLUSION: This paper depicts static abdominal thermography as a potential noninvasive tool for screening and surveillance of patients with extensive ulcerative colitis

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