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D. Stojanović, Živko Ćetojević, Boris Dujaković, M. Stanetić, T. Kovacevic-Preradovic, Bojan Stanetic

Introduction: Since December 2019, the humanity is constantly under affection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite global dissemination, neither the treatment or the specific predictive factors have been found or strictly defined yet. Aim: Aim of this study was to assess the long-term (1 year) predictive value of high-sensitive Troponin T (hsTnT) in COVID-19 affected, hospitalised patients. Methods: Between 5 March 2020 and 31 March 2020, 87 consecutive patients hospitalised at University Clinical Centre of the Republic of Srpska due to SARS-CoV2caused pneumonia, in whom hsTnT was measured, were included. The Kaplan-Meier analysis was used to assess differences in all-cause mortality between the groups. Independent predictors of all-cause mortality were identified through univariateand multivariate Cox regression analysis. Results: Compared with patients who had normal hsTnT levels, patients with raised hsTnT were significantly older (70.7 ± 13.23 vs 49 ± 15.29; p < 0.001). Glucose values were significantly increased in patients with raised hsTnT (9.29 ± 5.14 vs 6.76 ± 2.46 [4.1-5.9] mmol/L; p = 0.005), as well as serum creatinine (179.07 ± 225.58 vs 87.53 ± 18.16 μmol/L; p = 0.01), hsTnT (187.43 ± 387.29 vs 7.58 ± 3.40 pg/mL; p = 0.003), D-dimer (5.94 ± 13.78 vs 1.04 ± 1.26 [0-0.50] mg/L; p = 0.024), C-reactive protein (125.92 ± 116.82 vs 69.97 ± 73.09) [< 5.0] mg/L; p = 0.009) and calcium (1.32 ± 0.46 vs 1.03 ± 0.173 [2.20-2.65] mmol/L; p = 0.001). Kaplan-Meier analysis revealed that the number of all-cause deaths at 1 year was 19 of whom 18 were presented with elevated hsTnT (log-rank p < 0.001). When univariate Cox regression was applied, multiple predictors of all-cause mortality have been identified ie age, haemoglobin, haematocrit, urea, CK-MB as well as hsTnT. In a multiple regression model, hsTnT remained an independent predictor of poor outcome. Conclusion: Results from this study showed that the value of hsTnT during hospitalisation is possibly associated with long-term poor outcome of COVID-19 patients. Therefore, hsTnT may appear as a surrogate factor to differentiate between patients at high risk who need more intensive follow-ups.

Vesna Paušić, G. Jovanović, S. Simic, J. Knežević

Introduction. Mirror therapy was developed by Vilayanur Subramanian Ramachandran for the treatment of phantom pain after limb amputation. Mirror therapy is a neurorehabilitation technique that helps to relearn the use of affected limbs on many neurological and psychological levels. Material and Methods. A literature review was conducted using the following databases: KOBSON, Google Scholar, PubMed and MEDLINE. Results. A systematic literature review has shown that there is insufficient evidence of the effectiveness of this treatment in relieving and suppressing phantom limb pain. The results indicate the effectiveness of mirror therapy in relieving pain in people after a stroke. The small amount of evidence and lack of methodology reports have a major impact on the quality of this evidence. After mirror therapy, a significant reduction in pain at rest and during active movement was reported. Conclusion. Further research on mirror therapy is needed to help relieve pain. Evidence of the effectiveness of mirror therapy on pain has not been sufficiently investigated so far.

Margherita Cappelletto, R. Santoleri, L. Evangelista, F. Galgani, E. Garcés, Alessandra Giorgetti, F. Fava, B. Herut et al.

This paper presents major gaps and challenges for implementing the UN Decade of Ocean Science for Sustainable Development (2021-2030) in the Mediterranean region. The authors make recommendations on the scientific knowledge needs and co-design actions identified during two consultations, part of the Decade preparatory-phase, framing them in the Mediterranean Sea’s unique environmental and socio-economic perspectives. According to the ‘Mediterranean State of the Environment and Development Report 2020’ by the United Nations Environment Programme Mediterranean Action Plan and despite notable progress, the Mediterranean region is not on track to achieve and fully implement the Sustainable Development Goals of Agenda 2030. Key factors are the cumulative effect of multiple human-induced pressures that threaten the ecosystem resources and services in the global change scenario. The basin, identified as a climate change vulnerability hotspot, is exposed to pollution and rising impacts of climate change. This affects mainly the coastal zones, at increasing risk of extreme events and their negative effects of unsustainable management of key economic assets. Transitioning to a sustainable blue economy is the key for the marine environment’s health and the nourishment of future generations. This challenging context, offering the opportunity of enhancing the knowledge to define science-based measures as well as narrowing the gaps between the Northen and Southern shores, calls for a joint (re)action. The paper reviews the state of the art of Mediterranean Sea science knowledge, sets of trends, capacity development needs, specific challenges, and recommendations for each Decade’s societal outcome. In the conclusions, the proposal for a Mediterranean regional programme in the framework of the Ocean Decade is addressed. The core objective relies on integrating and improving the existing ocean-knowledge, Ocean Literacy, and ocean observing capacities building on international cooperation to reach the “Mediterranean Sea that we want”.

Margherita, Cappelletto, Rosalía, Santoleri, Lorenza, Evangelista, François, Galgani et al.

Sonja T Marinković, Đ. Đukanović, N. Mandić-Kovačević, T. Cvjetković, S. Uletilović, Ž. Maksimović

Background/Aim: Organophosphorus compounds (OP) bind to acetylcholinesterase (AChE) causing an irreversible inhibition of the enzyme. When doing in vivo studies of OP intoxication, to precisely measure AChE activity in the brain tissue it is necessary to remove as much blood from the brain as possible. By doing so, interference of the OPs present in the blood is avoided. Usually this demands expensive equipment, therefore, the aim of this study was to find a simple and economical method to eliminate the blood from brain blood vessels. Methods: Wistar albino rats were divided into four groups named Control (C), Control washout (CW), Paraoxon (Pox) and Paraoxon washout (PoxW) group. Rats in Pox and PoxW were treated with 0.25 mg/kg paraoxon subcutaneously (sc), while C and CW received 1 mL/kg sc saline instead. The "Marinković-Maksimović" ("MM") method was performed in rats from PoxW and CW groups. Activity of AChE was measured both in erythrocyte lysate and in brain tissue using spectrophotometry. Results: Macroscopic examination revealed that the elimination of blood was achieved in CW and PoxW groups. Activity of AChE in homogenised brain tissue was expectedly lower in the Pox and PoxW group, when compared to C and CW group, respectively. The CW group had a lower value of AChE activity in the brain tissue compared to C group, while activity of AChE in the PoxW group was statistically higher than in the Pox group (p = 0.044). Conclusion: The MM method provides good elimination of blood from the brain. Together with blood, present confounding factors that interfere with analysis in homogenised brain tissue, were also eliminated.

D. Lončar-Stojiljković, Ž. Maksimović, M. Đurić

Background/Aim: In surgery, and especially in the neurosurgical operations, maintenance of cardiovascular stability during and in the phase of the immediate postoperative recovery is of vital importance. The aim of this study was to investigate the effects of continuous esmolol infusion on the values of cardiovascular parameters and quality of the emergence from anaesthesia in neurosurgical patients. Methods: A total of 40 patients of both sexes scheduled for elective supratentorial surgery were randomly assigned to two groups. Esmolol group received intravenous (iv) infusion of esmolol dissolved in 5 % glucose solution (during the first 5 min at a rate of 0.3 mg/kg/min and thereafter at a rate of 0.1 mg/kg/min), while the ones from the control group received a 5 % glucose solution without esmolol at the same volume and rate. Cardiovascular parameters were registered at critical phases of anaesthesia and operation (induction, intubation, placement of Mayfield frame, craniotomy, skull closure, extubation). Recovery after anaesthesia was assessed based on times of eye opening on command, spontaneous eye opening and regaining of full orientation. Results: Values of systolic blood pressure and heart rate were significantly lower in the esmolol than in the control group of patients. Although the durations of anaesthesia did not differ, patients from the esmolol group required significantly less opioids and isoflurane and recovered after the anaesthesia significantly faster than the patients in the control group. Conclusion: Ultrashort-acting beta-adrenergic receptor antagonist esmolol, administered as a continuous iv infusion, assures better cardiovascular stability and smoother emergence from the balanced inhalation general anaesthesia than the control glucose infusion in elective neurosurgical patients.

Introduction: Oganophosphorus compounds (OP) bind to acetylcholinesterase (AChE) and inactivate it. In the synaptic cleft, undestroyed and accumulated acetylcholine produce the acute cholinergic effects. The aim of this study was to determine the frequency, speed of onset and intensity of certain signs of paraoxon poisoning depending on dose and outcome of poisoning. Methods: The study was conducted in adult Wistar rats. The median lethal dose (LD50) of paraoxon as well as protective ratio (PR) of atropine (10 mg/kg intramuscularly) was determined. Clinical signs of poisoning were observed: fasciculations, tremor, seizures, ataxia, piloerection, lacrimation, exophthalmos, bizzare/stereotypic behaviour and dyspnoea. The time from paraoxon injection to the first appearance of the sign of poisoning was recorded as well as the intensity of poisoning with evaluation at 10 time intervals throughout the 4 h observational period. Results: The LD50 of paraoxon was 0.33 mg/kg (subcutaneously) and PR of atropine was 2.73. Dose-dependent, piloerection occurred more often (p = 0.009) and at higher intensity (p = 0.016) at higher doses. Fasciculations, tremor, seizures and ataxia occurred significantly earlier at higher doses of paraoxon (p = 0.015, 0.002, 0.021 and 0.016, respectively), as well as the intensity of seizure, tremor and fasciculation. Piloerection (p = 0.002) and seizures occurred more frequently (p = 0.009) in non-survivors. Fasciculations, tremor, seizures and ataxia occurred significantly earlier and at higher intensity in non-survivors (p < 0.001, for all parameters), as well as dyspnoea (p = 0.009 and p = 0.048). In atropine-protected rats, nicotinic effects persevered, so they were the prognostic parameter of the severity of the poisoning. Conclusion: Seizures and fasciculations followed by tremor were strong prognostic parameters of the probability of lethal outcome of paraoxon poisoning. Also, the mentioned poisoning signs were with their intensity and speed of occurrence in a clear positive correlation with the administered dose of paraoxon. Even at high doses of paraoxon, atropine blocked the muscarinic (but not nicotinic) effects and somewhat mitigated the CNS toxic effects.

D. Mihajlović, Biljana Mihajlović, N. Todorović, Ž. Maksimović

Background / Aim: More people die each year due to cardiovascular diseases (CVDs) than from any other cause. The most common cause of ischaemic heart diseases (IHD) is atherosclerosis of the coronary arteries. Risk factors for the development of coronary heart disease (CHD) can be preventable and non-preventable. The aim of the study was to determine the frequency of individual risk factors in patients with CHD. Methods: Retrospective analysis included patients with diagnoses of stable angina pectoris (AP), unstable angina pectoris and myocardial infarction - acute coronary syndrome (ACS) and ischaemic cardiomyopathy (iCMP). The prevalence of the following risk factors for IHD was analysed: hypertension, diabetes, obesity, cholesterol, smoking, family history, age and sex. Data were taken from the Register of Patients with Chronic Diseases and Risk Factors and electronic patient records. Results: Of the total number of respondents older than 18, 4.95 % had CHD. Of the 178 patients with IHD, 70 (39.3 %) patients had AP, 60 (33.7 %) patients had ACS and 48 (27.0 %) patients had iCMP. Positive family history had 63.5 % of patients, 72 % were older than 66, 24.1 % were smokers and 74.2 % of patients had elevated blood cholesterol levels. Diabetes mellitus affected 29.2 % of patients, hypertension 88.8 %, and BMI ≥ 25 kg/m2 had 70.8 % of patients. Of the total number of patients with ACS, 68.3 % were men, while higher percentage of women suffered from AP (62.9 %) (p = 0.002). In the age below 65, CHD was more common in men (p = 0.007). Cholesterol was elevated more often in patients with AP than iCMP (p = 0.001). Patients with ACS were more likely to have diabetes mellitus compared to patients with AP and iCMP (p = 0.010). Conclusion: The prevalence of preventable risk factors is alarmingly high. Of particular importance is the timely detection and treatment of risk factors by family physicians and strengthening the personal responsibility of each individual in choosing their lifestyle and active involvement in the therapeutic process.

The vascular approach is a prerequisite for performing hemodialysis, but their "weak points" are different and frequent complications. Modern guidelines recommend native arteriovenous fistula (AVF) as the first choice of vascular approach because it is characterized by the longest survival and the least complications compared to other vascular approaches. All complications of AVF can be divided into intraoperative, early, and late postoperative. This paper presents the late postoperative complications of AVF, their frequency, causes, diagnosis and treatment. The most important late postoperative complications are: stenosis, thrombosis, aneurysm or pseudoaneurysm formation, infection, hand edema, hematoma, ischemic steal syndrome, ischemic neuropathy, congestive heart failure. Large differences in the frequency of each complication in earlier studies can be explained by differences in surgical technique, localization of AVF, diagnostic methods, but, above all, differences between the presented groups of patients. It is described that the age of patients, sex, underlying disease, the presence of comorbid conditions and various metabolic and immune disorders characteristic of chronic renal failure, as well as the way of using and caring for AVF significantly affect the occurrence of AVF complications. One of the main predictors of AVF success and survival is the quality of the patients' blood vessels, and therefore careful examination of blood vessels before approaching AVF creation is of particular importance. The creation, use and care of AVF is the task of the team of health professionals who take part in the treatment of these patients, and successful treatment requires their good cooperation, as well as cooperation with patients.

Danijela Kuhajda, Ivan Kuhajda, M. Ilic, S. Maksimovic, Jelena Crnobrnja, Nensi Lalić, M. Bojović

Introduction/Objective. Chronic obstructive pulmonary disease (COPD) is a primary lung disease. Today, pulmonary rehabilitation (PR) is the basis of non-pharmacological treatment of these patients, with numerous confirmed effects on the most significant symptoms of the disease and quality of life (QoL). The aim of this study was to determine the relationship between certain risk factors and the outcome of PR, as well as to determine the percentage of respondents who had a positive outcome of PR. Methods. The study included 500 patients with COPD, determined according to the guidelines of the GOLD, all stages I-IV, in the stable phase of the disease, who completed the outpatient PR program. Disease stage, comorbidities, forced expiratory volume in the first second, 6-minute walk test (6MWT), COPD Assessment Test (CAT) and Medical Research Council dyspnea scale, BODE index, were measured before and after the program. The last four parameters have been observed as risk factors that affect the outcome of PR, but also as parameters by which we monitor the outcome of PR. Results. A successful outcome of PR was achieved by as many as 452 (90.4%) patients. As independent predictors of a positive outcome of PR were determined: lower number of comorbidities, absence of heart failure, higher BMI and CAT ? 10. Conclusions. PR in our group of patients leads to statistically significant improvements in most of the examined subjective and objective parameters, in patients at all stages of the disease.

D. Tegeltija, A. Lovrenski, Tijana Vasiljević, S. Maksimovic

Introduction/Objective. The presence of epidermal growth factor receptor (EGFR) mutations is the best predictor of response for therapy with tyrosine kinase inhibitors. In this study, we investigate association between EGFR mutations and clinicopathological characteristics and thyroid transcription factor (TTF-1) expression in lung adenocarcinomas (AD). Methods. We analyzed 142 surgical samples from patients with histologically confirmed lung AD from January 2010 to December 2015. All tumor tissues were reclassified according to the World Health Organization criteria and EGFR mutations detected by real-time polymerase chain reaction. TTF-1 expression was detected by immunohistochemistry in 83 out of 142 cases. The association between EGFR and TTF-1 expression was analyzed using the ?2 test or Fisher?s exact test with SPSS software version 20.0. Results. This study included 78 male and 64 women with a median age of 61.6 (range, 42?82) years. Acinar (ACN) and solid (SOL) were the most common histological types (47.9% and 38.7%, respectively). TTF-1 expression was present in 69 of 83 (83%) ADs. The EGFR mutation was found in 7%, more frequently in women, and patients with smoking history, and acinar type of AD, whereas it had no association with age and pathological stage and TTF-1 expression. Conclusion. In conclusion, the results of this study demonstrate that the presence of EGFR mutations is associated with some clinical characteristics and histologic type of ADs, but not with TTF-1 expression.

S. Štrbac, Nataša Pilipović-Broćeta, N. Todorović, V. vujić-Aleksić, Siniša Stević, A. Lolić, A. Šeranić, D. Vulic et al.

Background/Aim: The prevention of cardiovascular risk factors and cardiovascular disease management contributes to the cardiovascular mortality reduction. The effects of these activities have been measured by quality indicators. The aim of this study was to determine the effects of family medicine team training workshop and implementation of clinical guidelines on the cardiovascular risk factors and diseases management in primary health care in the Republic of Srpska/Bosnia and Herzegovina. Methods: The "CardioVascular Risk Assessment and Management" study included a sample of 373 teams from 41 primary health care centres trained to provide adequate services and to compare the quality of cardiovascular risk management before and after the training workshop and implementation of clinical guidelines. The comparison was based on nine project defined performance indicators related to hypertension, type 2 diabetes mellitus, hyperlipidaemia, tobacco smoking and obesity. Results: Significant improvements were observed in six indicators after the training workshop and implementation of guidelines. Target values for blood pressure and HbA1c were achieved in over 80 % of patients (82.12 ± 15.81 vs 84.49 ± 12.71 and 84.49 ± 12.71 vs 85.49 ± 24.55; before and after the training workshop, respectively), while the target values for LDL cholesterol were achieved in 54.98 % ± 20.33 before and 57.64 % ± 16.66 after the training workshop. The number of teams that had less than 20 % of recorded data significantly decreased after the training workshop and guidelines implementation, and adequate recording of all indicators was improved. Conclusion: The training workshop of family medicine teams and implementation of clinical guidelines resulted in significant quality improvement of cardiovascular diseases management in primary health care.

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