Medicina, Volume 54, Issue 2 (May 2018) – 21 articles

Background and objectives: The importance of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) has been re-established in recent years aiming at fewer metastatic sites and better control of the disease. We prospectively studied the possibility of early prediction of overall survival (OS) and progression-free survival (PFS) after 3 cycles of chemotherapy with doxetacel, cisplatin and 5-fluorouracil using 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (¹⁸F-FDG PET/CT) in patients with head and neck squamous cell cancer. To our knowledge, this is the first such study. Materials and Methods: Thirty-five patients were studied. They underwent an ¹⁸F-FDG PET/CT examination twice: a day before ICT and 10–14 days after the last cycle of ICT. Tumor-standardized uptake value (SUVmax) and hypermetabolic tumor volume were measured on both scans. The mean age of patients was 56.5 years. Complete responses to CCRT PFS and OS were calculated. Results: Our results showed that a decrease of ≥30% in the SUVmax value after ICT was a prognostic factor of tumor response to PFS and OS (p = 0.026 and p = 0.021). The groups of patients with a SUVmax between 10 and 14.5 in the primary tumor on a pre-ICT ¹⁸F-FDG PET/CT scan had statistically shorter PFS and OS (p = 0.001, p = 0.006) when compared with other groups of patients with SUVmax less than 10 or SUVmax more than 14.5. A decrease of less than 55% of hypermetabolic tumor volume of the primary tumor was significantly related to poor prognosis in PFS and OS (p = 0.033, p = 0.017). Conclusions: SUVmax and hypermetabolic tumor volume measured on ¹⁸F-FDG PET/CT after ICT might be valuable prognostic tools for predicting OS and PFS and, thus, for the selection of patients with head and neck cancer who will benefit from CCRT. Full article

Background and objective: Irrational use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the main cause of adverse effects-associated hospitalizations among all medication groups leading to extremely increased costs for health care. Pharmacoepidemiological studies can partly reveal such issues and encourage further decisions. Therefore, the aim of our study was to evaluate the utilization of non-opioid analgesics (ATC classification N02B and M01A) in Lithuania, and to compare it with that of other Baltic and Scandinavian countries in terms of compliance to the WHO pain treatment guidelines and the EMA safety recommendations on NSAID use. Materials and methods: The dispensing data were obtained from the sales analysis software provider in the Baltic countries (SoftDent, Ltd., Kaunas, Lithuania); State Medicine Control Agencies of Lithuania, Latvia, and Estonia; Norwegian Prescription Database; Swedish Database for Medicines; and Danish Prescription Database. Data included the utilization of both prescription and over-the-counter drugs. Utilization was expressed in defined daily doses (DDD)/1000 inhabitants/day. Results: During the 11-year period, the utilization of drugs belonging to the N02B and M01A groups increased by 22.8%, from 58.37 in 2005 to 71.68 DDD/1000 inhabitants/day in 2016 in Lithuania. Contrary to the WHO guidelines on pain management, all Baltic countries were more likely to use NSAIDs than other analgesics and antipyretics: in 2015, the drugs of the M01A group were used 6.04, 5.79, and 6.11 times more than those of N02B in Lithuania, Estonia, and Latvia, respectively, whereas the Scandinavian countries preferred the N02B to the M01A group: in Denmark and Sweden, the utilization of other analgesics and antipyretics was 2.33 and 1.24, respectively, times higher than that of NSAIDs. In Norway, the use of both groups was similar. In the Scandinavian countries, paracetamol was the analgesic of first choice, whereas, in Lithuania, it took only the third place. The most popular drug in Lithuania was diclofenac, and its utilization accounted for 30.04% of all non-opioid analgesics in 2016. Although the European Medicines Agency (EMA) restricted the use of certain NSAIDs, i.e., cyclooxygenase-2 (COX-2) inhibitors, nimesulide, and diclofenac, their use consistently increased by 15.91, 2.83, and 1.41 times, respectively, showing incompliance with the international guidelines. Conclusions: Neither the EMA safety policy on NSAID use nor the WHO pain treatment guidelines had a sufficient impact on the rational use of NSAIDs in Lithuania. The use of NSAIDs restricted by the EMA (diclofenac, COX-2 inhibitors, nimesulide, and piroxicam) remains high or even increases, while the utilization of safer alternatives (paracetamol and naproxen) remains relatively low as compared with the Scandinavian countries. Incompliance with international guidelines may result in increased morbidity, mortality and higher costs for health care. Full article

Background and objective: Optic neuritis (ON) is characterized by painful, usually monocular vision loss with decreased visual acuity and defects of the visual field and color vision. The etiology and pathophysiology of ON is not completely clear. It is thought that a matrix metalloproteinase 2 (MMP-2) gene plays an essential role in this autoimmune inflammatory disease. The aim of this study was to determine the relationship between the MMP-2 (-1306 C/T) rs243865 gene polymorphism and ON, and that of ON with multiple sclerosis. Materials and methods: Patients with ON/ON and multiple sclerosis and a control group of healthy individuals were enrolled in this study. The genotyping test of the MMP-2 (-1306 C/T) was carried out using a real-time polymerase chain reaction (PCR) method. Results: Analysis revealed that T allele at the MMP-2 (-1306 C/T) was less frequent in the ON group compared to the control group (14.5% vs. 23.3%, p = 0.031), and was associated with decreased likelihood of ON development (OR = 0.566; 95% CI: 0.333-0.962; p = 0.036). No significant associations were revealed while comparing the subgroups of ON patients with and without multiple sclerosis. Conclusion: The MMP-2 (-1306 C/T) gene polymorphism was found to be associated with ON development. Full article

Background and Objective: Hearing loss is the most common sensory deficit in humans. The aim of this study was to clarify the genetic aetiology of nonsyndromic hearing loss in the Moravian-Silesian population of the Czech Republic. Patients and Methods: This study included 200 patients (93 males, 107 females, mean age 16.9 years, ranging from 4 months to 62 years) with nonsyndromic sensorineural hearing loss. We screened all patients for mutations in GJB2 and the large deletion del(GJB6-D13S1830). We performed further screening for additional genes (SERPINB6, TMIE, COCH, ESPN, ACTG1, KCNQ4, and GJB3) with Sanger sequencing on a subset of patients that were negative for GJB2 mutations. Results: We detected biallelic GJB2 mutations in 44 patients (22%). Among these patients, 63.6%, 9.1% and 2.3% exhibited homozygous c.35delG, p.Trp24*, and p.Met34Thr mutations, respectively. The remaining 25% of these patients exhibited compound heterozygous c.35delG, c.-23+1G>A, p.Trp24*, p.Val37Ile, p.Met34Thr, p.Leu90Pro, c.235delC, c.313_326del14, p.Ser139Asn, and p.Gly147Leu mutations. We found a monoallelic GJB2 mutation in 12 patients (6.6%). We found no pathogenic mutations in the other tested genes. Conclusions: One fifth of our cohort had deafness related to GJB2 mutations. The del(GJB6-D13S1830), SERPINB6, TMIE, COCH, ESPN, ACTG1, GJB3, and KCNQ4 mutations were infrequently associated with deafness in the Moravian-Silesian population. Therefore, we suggest that del(GJB6-D13S1830) testing should be performed only when patients with deafness carry the monoallelic GJB2 mutation. Full article

Introduction. The immunosuppression used after transplantation (Tx) is associated with an increased risk of opportunistic infections. In Europe, parasitic infections after Tx are much less common than viral, bacterial and fungal ones. However, diseases caused by parasites are very common in tropical countries. In the last years the number of travellers with immunosuppression visiting tropical countries has increased. Methods. We performed a literature review to evaluate a risk of parasitic infections after Tx in Europe. Results. There is a real risk of parasitic infection in patients after Tx travelling to tropical countries. Malaria, leishmaniasis, strongyloidiasis and schistosomiasis are the most dangerous and relatively common. Although the incidence of these tropical infections after Tx has not increased, the course of disease could be fatal. There are also some cosmopolitan parasitic infections dangerous for patients after Tx. The greatest threat in Europe is toxoplasmosis, especially in heart and bone marrow recipients. The most severe manifestations of toxoplasmosis are myocarditis, encephalitis and disseminated disease. Diarrhoea is one of the most common symptoms of parasitic infection. In Europe the most prevalent pathogens causing diarrhoea are Giardia duodenalis and Cryptosporidium. Conclusions. Solid organ and bone marrow transplantations, blood transfusions and immunosuppressive treatment are associated with a small but real risk of parasitic infections in European citizens. In patients with severe parasitic infection, i.e., those with lung or brain involvement or a disseminated disease, the progression is very rapid and the prognosis is bad. Establishing a diagnosis before the patient’s death is challenging. Full article

Background: new minimally invasive sternotomy (mini-sternotomy) procedures have improved the treatment outcome and reduced the incidence of perioperative complications leading to improved patient satisfaction and a reduced cost of aortic valve replacement in comparison to the conventional median sternotomy (full sternotomy). The aim of this study is to compare and gain new insights into operative and early postoperative outcomes, long-term postoperative results, and 5-year survival rates after aortic valve replacement through a ministernotomy and full sternotomy. Methods: This is a retrospective study of patients who underwent an isolated replacement of the aortic valve via a full sternotomy or ministernotomy from 2011 to 2016. From 2011 to 2016, 426 cardiac interventions were performed, 70 of which (16.4%) were of the ministernotomy and 356 (83.6%) of the full sternotomy. Through propensity score matching, 70 patients who underwent the ministernotomy (ministernotomy group) were compared with 70 patients who underwent the full sternotomy (control group). Results: in the propensity matching cohort, no statistical difference in operative time was noted (p = 0.856). The ministernotomy had longer cross clamp (88.7 ± 20.7 vs. 80.3 ± 24.6 min, p = 0.007) and bypass (144.0 ± 29.9 vs. 132.9 ± 44.9 min, p = 0.049) times, less ventilation time (9.7 ± 1.7 vs. 11.7 ± 1.4 h, p < 0.001), shorter hospital stay (18.3 ± 1.9 vs. 21.9 ± 1.9 days, p = 0.012), less 24-h chest tube drainage (256.2 ± 28.6 vs. 407.3 ± 40.37 mL, p < 0.001), fewer corrections of coagulopathy (p < 0.001), fewer patients receiving catecholamine (5.71 vs. 30.0%, p < 0.001) and better cosmetic results (p < 0.001). Moreover, the number of patients without complaints at 1 year after the operation was significantly greater in the ministernotomy group (p = 0.002), and no significant differences in the 5-year survival between the groups were observed. In the overall cohort, the ministernotomy had longer cross clamp times (88.7 ± 20.7 vs. 79.9 ± 24.8 min, p < 0.001), longer operative times (263.5 ± 62.0 vs. 246.7 ± 74.2 min, p = 0.037) and bypass times (144.0 ± 29.9 vs. 132.7 ± 44.5 min, p = 0.026), lower incidence of 30-day mortality (1(1.4) vs. 13(3.7), p = 0.022), shorter hospital stays post-surgery p = 0.025, less 24-h chest tube drainage, p < 0.001, and fewer corrections of coagulopathy (p < 0.001). Conclusions: the ministernotomy has a number of advantages compared with the full sternotomy and thus could be a better approach for aortic valve replacement. Full article

Aim: Data on the prevalence of vitamin D deficiency in Lithuania are scarce. The aim was to assess the reserves of vitamin D in different age groups of out-patients, regarding the season of the year. Methods: Data on serum 25-hydroxyvitamin D (25(OH)D) levels from blood tests made in 2012–2014 were obtained from one laboratory, and a retrospective cross-sectional analysis was performed. Results: A total of 9581 subjects were included. The mean age of the participants was 33 ± 23 years. The mean levels of vitamin D were higher in males than in females (p < 0.001). The highest mean 25(OH)D levels were in 0–9-year-old group, the lowest were in the 10–19-year-old group and in the group of participants that were 70 years and older (p < 0.001). The lowest vitamin D status was found in January, February, March, and April. The highest status was found in August and September. Overall, vitamin D deficiency, sufficiency, and hypervitaminosis were detected in 67%, 21%, and 12% of cases, respectively. Most cases with hypervitaminosis were in the group of children up to 2 years of age. Conclusion: Vitamin D status demonstrated clear seasonality. Significant sex-related differences of vitamin D statuses were also determined. Vitamin D deficiency was very prevalent in almost all age groups. Young children (aged up to 2 years) are of special interest for further research involving other types of 25(OH)D assays, such as those based on high-performance liquid chromatography (HPLC), since the real prevalence of “true” vitamin D hypervitaminosis in Lithuania’s children is still to be determined. Full article

Degenerative aortic stenosis (DAS) is the most frequently diagnosed heart valve disease in Europe and North America. DAS is a chronic progressive disease which resembles development of atherosclerosis. Endothelial dysfunction, lipid infiltration, calcification and ossification are evidenced in both diseases. The same risk factors such as older age, male sex, smoking, and elevated levels of lipids are identified. The effect of smoking, visceral obesity, metabolic syndrome, hypercholesterolemia, low-density lipoprotein, high-density lipoprotein, lipoprotein(a), adiponectin and apolipoprotein(a) on development of DAS are being studied. The search for genetic ties between disorders of lipid metabolism and DAS has been started. DAS is characterized by a long symptom-free period which can last for several decades. Aortic valve replacement surgery is necessary when the symptoms occur. The lipid-lowering therapy effect on stopping or at least slowing down the progression of DAS was studied. However, the results of the conducted clinical trials are controversial. In addition, calcium homeostasis, bone metabolism and calcinosis-reducing medication are being studied. Although prospective randomized clinical trials have not demonstrated any positive effect of statins used for slowing progression of the disease, statins are still recommended for patients with dyslipidemia. Recent study has suggested that a specific modification of treatment, based on severity of disease, may have a beneficial effect in patients with aortic sclerosis and mild DAS. New clinical studies analyzing new treatment possibilities which could correct the natural course of the disease and reduce the need for aortic valve replacement by surgery or transcatheter treatment interventions are needed. Full article

Typhoid fever causes significant morbidity and mortality in developing countries, with inaccurate estimates in some countries affected, especially those situated in Sub-Saharan Africa. Disease burden assessment is limited by lack of a high degree of sensitivity and specificity by many current rapid diagnostic tests. Some of the new technologies, such as PCR and proteomics, may also be useful but are difficult for low-resource settings to apply as point-of-care diagnostics. Weak laboratory surveillance systems may also contribute to the spread of multidrug resistant Salmonella serovar Typhi across endemic areas. In addition, most typhoid-endemic countries employ serological tests that have low sensitivity and specificity making diagnosis unreliable. Here we review currently available typhoid fever diagnostics, and advances in serodiagnosis of S. Typhi. Full article

Objective: The number of patients presenting with warfarin-associated intracranial bleeding and needing neurosurgical intervention is growing. Prothrombin complex concentrate (PCC) is commonly used for anti-coagulation reversal before emergent surgery. We present our experience with PCC use in patients presenting with coagulopathy and needing urgent craniotomy. Methods: We retrospectively identified all patients presenting with intracranial bleeding and coagulopathy due to warfarin use, requiring urgent neurosurgical procedures, from January, 2014 (implementation of 4-PCC therapy) until December, 2016. For coagulation reversal, all patients received 4-PCC (Octaplex) and vitamin K. Results: Thirty-five consecutive patients (17 men; median age 72 years) were administered 4-PCC before emergent neurosurgical procedures. The majority of patients presented with traumatic subdural hematoma (62%) and spontaneous intracerebral hemorrhage (32%). All patients were taking warfarin. Median international normalized ratio (INR) on admission was 2.94 (range: 1.20 to 8.60). Median 4-PCC dose was 2000 I.U. (range: 500 I.U. to 3000 I.U.). There was a statically significant decrease in INR (p < 0.01), PT (p < 0.01), and PTT (p = 0.02) after 4-PCC administration. Postoperative INR values were ≤3.00 in all patients, and seven (20%) patients had normal INR values. There were no 4-PCC related complications. Four (11%) patients developed subdural/epidural hematoma and 20 (57%) patients died. Mortality was associated with lower Glasgow coma scale (GCS) score. Conclusions: The 4-PCC facilitates INR reversal and surgery in patients presenting with warfarin-associated coagulopathy and intracranial bleeding requiring urgent neurosurgical intervention. Full article

Background: the main goal of the study was to investigate the prevalence of the articular cartilage defects (ACD) in the patellofemoral (PF) region of the knee joint based on the anatomical shapes of patella and its impact on the level of physical activity in the population needing arthroscopic procedures for all types of pathologies in the knee. Methods: The articular cartilage status of the PF region was obtained from 1098 arthroscopic procedures of the knee joint. The ACD were correlated to Wiberg’s shape of the patella and classified according to the degree, size and depth of the ACD in the PF region using the ICRS (International Cartilage Repair Society) system: group I consisting of patients with Wiberg type I shape (W1), group II—patients with Wiberg type II shape (W2) and group III—patients with Wiberg type III shape (W3). The Tegner physical activity scale was used to evaluate the physical activity of the patients. Results: The mean of ACD size (PF region) in the W3 group was 3.10 ± 0.99 cm², which was a statistically significantly larger area in comparison with the W1 (1.90 ± 0.63 cm²; p < 0.0000) and W2 (1.95 ± 0.71 cm²; p < 0.0000). The patients from the W3 group (mean 3.10 ± 0.99) were less physically active (<4 Tegner) compared to the W2 group (mean of 4.48 ± 0.88; p = 0.004) and W1 group (mean of 4.55 ± 0.72; p = 0.002). Conclusions: The patients with the Wiberg type III patella shape had a higher incidence and larger size of ACD in the PF of the knee compared to the groups of Wiberg type I and II. Wiberg III patients with a lower level of physical activity had a larger size of ACD in the PF joint. Full article

Enhanced recovery after surgery (ERAS) are specially designed multimodal perioperative care pathways which are intended to attain and improve rapid recovery after surgical interventions by supporting preoperative organ function and attenuating the stress response caused by surgical trauma, allowing patients to get back to normal activities as soon as possible. Evidence-based protocols are prepared and published to implement the conception of ERAS. Although they vary amongst health care institutions, the main three elements (preoperative, perioperative, and postoperative components) remain the cornerstones. Postoperative pain influences the quality and length of the postoperative recovery period, and later, the quality of life. Therefore, the optimal postoperative pain management (PPM) applying multimodal analgesia (MA) is one of the most important components of ERAS. The main purpose of this article is to discuss the concept of MA in PPM, particularly reviewing the use of opioid-sparing measures such as paracetamol, nonsteroid anti-inflammatory drugs (NSAIDs), other adjuvants, and regional techniques. Full article

Background and Objective: Endobronchial ultrasound (EBUS) is a minimally invasive endobronchial technique, which uses ultrasound along with a bronchoscope to visualize the airway wall and structures that are adjacent to it. Indications for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are samplings of mediastinal, hilar lymph nodes, and tumors adjacent to airway walls. EBUS-TBNA has been used in our clinic since 2009. The aim of the study is to evaluate the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of cytological and histological specimens, and the safety of EBUS-TBNA in an unselected patient population that has been referred to our hospital. Materials and Methods: We have retrospectively analyzed the medical documentation of 215 patients who had EBUS-TBNA performed in our clinic from April 2009 to February 2014. Results: There were 215 patients who underwent EBUS-TBNA. A total of 296 lymph nodes were sampled. EBUS-TBNA was diagnostic in 176 (81.9%) cases of cytological, 147 (68.4%) cases of histological, and 191 (88.9%) cases of the combined evaluation. In the lung cancer patients, EBUS-TBNA cytology had a sensitivity of 72.9% and histology of 72.9%, and in the sarcoidosis group, it had a cytology of 55.8% and histology of 64.5%. As all positive cytology and histology specimens were assumed to be true positive, specificity and positive predictive value (PPV) were 100%. The sensitivity and diagnostic accuracy was significantly higher when cytology and histology specimens were combined, compared with cytology or histology results evaluated separately (p < 0.05) (for lung cancer 84.1% and for sarcoidosis 78.8%). The sensitivity and diagnostic accuracy of EBUS-TBNA procedures increased significantly over time, with increased experience. There were no complications with EBUS-TBNA in our clinical practice. Conclusions: EBUS-TBNA had a high diagnostic yield and was safe in the diagnosis of lung cancer and sarcoidosis. It was most informative when cytology and histology were combined. The informative value of EBUS-TBNA histology increased with our experience. Full article

Lactose-derived prebiotics provide wide ranges of gastrointestinal comforts. In this review article, the probable biochemical mechanisms through which lactose-derived prebiotics offer positive gastrointestinal health are reported along with the up-to-date results of clinical investigations; this might be the first review article of its kind, to the best of our knowledge. Lactose-derived prebiotics have unique biological and functional values, and they are confirmed as ‘safe’ by the Food and Drug Administration federal agency. Medical practitioners frequently recommend them as therapeutics as a pure form or combined with dairy-based products (yoghurt, milk and infant formulas) or fruit juices. The biological activities of lactose-derived prebiotics are expressed in the presence of gut microflora, mainly probiotics (Lactobacillus spp. in the small intestine and Bifidobacterium spp. in the large intestine). Clinical investigations reveal that galacto-oligosaccharide reduces the risks of several types of diarrhea (traveler’s diarrhea, osmotic diarrhea and Clostridium difficile associated relapsing diarrhea). Lactulose and lactosucrose prevent inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). Lactulose and lactitol reduce the risk of hepatic encephalopathy. Furthermore, lactulose, galacto-oligosaccharide and lactitol prevent constipation in individuals of all ages. It is expected that the present review article will receive great attention from medical practitioners and food technologists. Full article

Background: Recently proposed histopathological classification may predict patient outcome in pauci-immune glomerulonephritis. This study sought to prove that the prognostic effect could be extended to all types of rapidly progressive glomerulonephritis. Methods: Retrospective analysis of patients diagnosed with rapidly progressive glomerulonephritis between April 1999 and August 2015 was performed. Epidemiological and clinical data were collected from medical records. The descriptions of renal biopsies were reviewed and classified into focal, sclerotic, crescentic and mixed class according to classification proposed by Berden et al. The study end points were end stage renal disease (ESRD) or death. Survival analyses were modelled using Cox regression. Results: 73 renal biopsies with diagnosis of rapidly progressive glomerulonephritis were included in the study. 25 (34.2%), 16 (21.9%), 24 (32.9%) and 8 (11%) patients were assigned to focal, crescentic, mixed and sclerotic class, respectively. Thirty-two (42.5%) patients were anti-neutrophil cytoplasmic antibody (ANCA) negative, of which eight (10.9%) were anti–glomerular basement membrane antibody (anti–GBM) positive and 24 (32.8%) were negative for autoimmune antibodies. Six (8.2%) patients died within one year. Among patients who survived, median change in estimated glomerular filtration rate (eGFR) values were: −10.5 mL/min in focal, 4.2 mL/min in crescentic, −4.3 mL/min in mixed and 4.1 mL/min in sclerotic group, p > 0.05. In the Cox regression model, there was no significant predictor of patient survival whereas the sclerotic group (HR 3.679, 95% CI, 1.164–11.628, p < 0.05) and baseline eGFR of <15 mL/min (HR 4.832, 95% CI, 1.55–15.08, p < 0.01) had an unfavorable effect for renal survival. Conclusions: Predominant glomerular sclerosis and low eGFR at baseline are associated with higher risk of ESRD in cases with crescentic glomerulonephritis. Therefore, despite the origin of injury, histological classification might aid in prediction of patient outcomes in rapidly progressive glomerulonephritis. Full article

Background and objective: Corneal neovascularization (CNV) is a vision-threatening condition arising from various corneal diseases. The aim of this study is to compare the effectiveness of bevacizumab and interferon alpha-2a (IFNα-2a) treatment on corneal neovascularization. Materials and Methods: Twenty-four Wistar albino rats were used in this study. After cauterization of the cornea with a silver nitrate applicator stick, the control group received 0.1 mL saline solution, the second group received 0.1 mL IFNα-2a (IFNα-2a, 6 million international units [MIU]/0.5 mL), and the third group received 2.5 mg bevacizumab by subconjunctival injection. An additional injection was administered to each group on the fourth day. After one week, the corneal neovascularization rate and the longest neovascular sprout length were determined. Results: The neovascularization rate (saline 0.65 ± 0.05; IFNα-2a 0.62 ± 0.07; bevacizumab 0.42 ± 0.11) with bevacizumab was significantly lower, more than those with IFNα-2a and saline (p < 0.001 and p < 0.001). The longest neovascular sprout length (saline, 4.00 ± 0.6 mm; IFNα-2a, 3.63 ± 0.52 mm; bevacizumab, 2.81 ± 0.65 mm) with bevacizumab was significantly shorter than those with saline and IFNα-2a (p = 0.001 and p = 0.012). Conclusions: Subconjunctival IFNα-2a has limited efficacy in the treatment of corneal neovascularization. Full article

Introduction: The estimates of the economic burden of smoking provide the basis for a comprehensive assessment of the overall economic impact and evidence for potential public health policy intervention by the government. The aim of this paper is to estimate the smoking-attributable direct healthcare expenditure covered by the Compulsory Health Insurance Fund (CHIF) in Lithuania in 2013. Methods: A prevalence-based and disease-specific annual cost approach was applied to 25 smoking-related diseases or disease categories. Our analysis included only direct government healthcare expenditure (reimbursed by CHIF), including: smoking-attributable outpatient and inpatient care services, medical rehabilitation, reimbursable and publicly procured pharmaceuticals and medical aids, the emergency medical aid (ambulance) service, nursing, and expensive tests and procedures. The smoking-attributable expenditure on the above-mentioned healthcare services was calculated by multiplying the total annual expenditure by the corresponding smoking attributable fractions (SAFs). Results: The total smoking-attributable government expenditure amounted to €37.4 million in 2013. This represented 3% of the total CHIF budget in 2013. Smoking-attributable expenditure on inpatient care and medical rehabilitation services was two times higher for male smokers, than for female smokers. Conclusions: Smoking imposes a significant preventable financial cost within the budget of the Lithuanian healthcare system. A quantitative estimation of smoking related healthcare costs could provide an incentive for the development of smoking cessation services, with additional attention towards male smokers, as well as an important focus on smoking prevention among children and youths. Full article

Background and Objective: In Wilson’s disease, copper metabolism is impaired due to defective copper transporting protein ATP7B, resulting in copper accumulation in liver and brain and causing damage to liver and brain tissues. Published data suggest that one of the possible treatments for Wilson’s disease is curcumin—a compound found in the root of Curcuma longa. In this study, we tested whether curcumin affects copper transport and excretion in HepG2 hepatocytes carrying wildtype ATP7B. Materials and Methods: We examined the impact of 5 µM and 25 µM curcumin on the transport of copper in HepG2 cells incubated with 20 µM and 100 µM CuCl₂, as well as copper excretion from cells. First, immunofluorescent staining and co-localization analysis were carried out in HepG2 cells using confocal laser scanning microscope and Nikon NIS Elements software. Second, a concentration of copper extracted into cell culture medium was determined using atomic absorption spectrometry. Results: The analysis of the co-localization between Golgi complex and ATP7B revealed that both 5 µM and 25 µM doses of curcumin improve the ability of liver cells to transport copper to plasma membrane at 20 µM CuCl₂, but not at 100 µM CuCl₂ concentration. However, atomic absorption spectrometry showed that curcumin rather promotes copper absorption into liver cell line HepG2 than excretion of it. Conclusions: Curcumin accelerates the transport of copper within liver cells, but does not promote copper excretion from HepG2 cells. Full article

Background: Evaluation of smell function is essential especially in cases of gradual deterioration, e.g., in neurodegenerative diseases, where rates of unawareness of the disorder are high and the importance of screening for olfactory dysfunction is increasing. To date, none of the tests for evaluation of olfactory dysfunction has been validated in Lithuania. The aim of the study was to develop a Lithuanian version of Sniffin’ Sticks 12 (SS12) odor identification test. Materials and Methods: The study was performed in 4 stages. The first stage included translation and back-translation from German, pilot group testing and language adaptation of the original SS12 test. In the second stage a survey group of 99 subjects was questioned for familiarity with the descriptors, used in the original version of the test. In the third stage after replacement of the least familiar distracters, a modified version of SS12 was created. Original and modified versions of SS12 were tested on 112 and 119 healthy subjects accordingly. The fourth stage of the study proved necessary as neither of the two SS12 versions turned out to be valid. After another round of replacement of the misleading distracters the second modified version of SS12 was created and it was tested on 115 healthy subjects. Results: Unsatisfactory correct identification rates of less than 75 percent in the same one item (lemon) were observed using both original and modified SS12 versions. With the second modification of distracters of SS12, identification of lemon increased significantly and overcame 75 percent. The decrease of SS12 scores in relation to age was ascertained in the study sample. Gender and smoking status did not prove to be independent predictors of SS12 scores in multiple linear regression analysis. Conclusion: The study presents an olfactory testing tool, which is adapted and modified culturally for use in the Lithuanian population. Full article

Cardiovascular abnormalities are widespread when a newborn is exposed to a hypoxic-ischemic injury in the neonatal period. Although the neuroprotective effects of levetiracetam (LEV) have been reported after hypoxia, the cardioprotective effects of LEV have not been documented. Therefore, we aimed to investigate whether levetiracetam (LEV) has a protective effect on cardiac-contractility and ultrastructure of heart muscle in rats exposed to hypoxia-ischemia (HI) during the neonatal period. A total of 49 seven-day-old rat pups were separated into four groups. For HI induction, a combination of right common carotid artery ligation with 8% oxygen in seven-day-old rat pups for 2 h was performed for saline, LEV100, and LEV200 groups. Just after hypoxia, LEV100 and LEV200 groups were administered with 100 mg/kg and 200 mg/kg of LEV, respectively. The arteries of rats in the control group were only detected; no ligation or hypoxia was performed. At the end of the 16th week after HI, cardiac mechanograms were recorded, and samples of tissue were explored by electronmicroscopy.While ventricular contractility in the control group was similar to LEV100, there were significant decreases in both saline and LEV200 groups (p < 0.05). Although ventricular contractile duration of the control and saline groups was found to be similar, durations in the LEV100 and LEV200 groups were significantly higher (p < 0.05). After HI, mitochondrial damage and ultrastructural deteriorative alterations in ventricles and atriums of the LEV-administered groups were significantly less severe than the saline group. The present study showed that neonatal HI caused long-term cardiac dysfunction and ultrastructural deteriorations in cardiac muscles. LEV administration just after HI might possess some protective effects against myocardial damage and contractility. Full article

Background and objectives: Cell culture is one of the mainstays in the research of breast cancer biology, although the extent to which this approach allows to preserve the original characteristics of originating tumor and implications of cell culture findings to real life situations have been widely debated in the literature. The aim of this study was to determine the role of three cell culture media on transcriptional expression of breast cancer markers in three breast cancer reference cell lines (MCF7, SkBr3 and MDA-MB-436). Materials and methods: Cell lines were conditioned in three studied media (all containing 5% fetal bovine serum (FBS) + hormones/growth factors; different composition of basal media) for four passages. Population growth was characterized by cumulative population doubling levels, average generation time, cell yield and viability at the fourth passage. Transcriptional expression of breast cancer differentiation markers and regulatory transcriptional programs was measured by qPCR. Results: Differences in the composition of growth media significantly influenced the growth of studied cell lines and the expression of mammary lineage governing transcriptional programs and luminal/basal markers. Effects of media on transcriptional expression were more pronounced in luminal cell lines (MCF7, SkBr3), than in the basal cell line (MDA-MB-436). Changes in growth media in terms of supplementation and basal medium delayed growth of cells, but improved cell yields. Conclusions: The expression of breast cancer cell differentiation phenotypic markers depends on the composition of cell growth medium, therefore cell culture as a tool in phenotypic studies should be used considering this effect. The findings of such studies should always be interpreted with caution. The formulation of cell growth media has greater effect on the expression of phenotypic markers in luminal, rather than basal cell lines. Media containing mitogens and higher vitamin content improved efficacy of cell culture in terms of cell yields, although greatly increased growth times. Full article