Search Results (13)

Background/Objectives: Cryotherapy is used for local tissue destruction through rapid freeze–thaw cycles. It induces cancer cell necrosis followed by inflammation in the treated tumor microenvironment, and it stimulates systemic adaptive immunity. Combining cryotherapy with immunotherapy may provide a sustained immune response by preventing T cell exhaustion. Methods: Fifty-five patients with metastatic non-small cell lung cancer who had received no prior treatment were randomized into two groups in a 1:1 ratio: the bronchoscopic cryotherapy group or the control group. Patients received up to four cycles of pembrolizumab as monotherapy or in combination with platinum-based chemotherapy. Immune-related adverse events (irAEs), complications, tumor size changes, overall response rate (ORR), and disease control rate (DCR) were evaluated. Results: Lung tumors, treated with cryotherapy, demonstrated continuous reduction from the baseline (22.4 cm² vs. 14.4 cm² vs. 10.2 cm², p < 0.001). Similar changes were observed in pulmonary tumors in the control group (19.0 cm² vs. 10.0 cm², p < 0.001). The median change in pulmonary tumors between two groups was not significant (−42.9% vs. −27.7%, p = 0.175). No significant differences were observed in the ORR (28.6% vs. 23.1%, p = 0.461) or target lesion decrease (−24.0% vs. −23.4%, p = 0.296) between the groups. However, the DCR was significantly higher in the cryotherapy group (95.2% vs. 73.1%, p = 0.049). No cases of serious bleeding during cryotherapy or pneumothorax were observed. Six patients (25.0%) in the cryotherapy group and eight (26.7%) in the control group experienced irAEs. Conclusions: Our study demonstrated that combined bronchoscopic cryotherapy and immunotherapy with or without chemotherapy may reduce the rate of progressive disease in metastatic non-small cell lung cancer patients while maintaining a satisfactory safety profile. Full article

Background and Objectives: Growing antibiotic resistance among bacteria is a global issue that is becoming harder and more expensive to solve. Traditional treatment options are becoming less effective, causing more fatal outcomes of nosocomial infections. Since the development of new antibiotics has stagnated in the last decade, a novel approach is needed. Materials and Methods: Graphene-based materials are being developed and tested for various applications, and the medical field is no exception. We tested 98 clinical A. baumannii strains for antibiotic resistance, AMP-C production and the effectiveness of a graphene oxide and silver nanoparticle hybrid nanocomposite. The disc diffusion method was used to determine antibiotic susceptibility results. Antibiotic discs containing cefotaxime, cloxacillin and clavulanate were used to detect AMP-C production. The effectiveness of the GO–Ag hybrid nanocomposite was determined by counting colony forming units (CFUs) after a suspension of A. baumannii and the GO–Ag hybrid nanocomposite was plated on MH agar and incubated overnight to grow colonies. Results: In our research, we found that A. baumannii strains are resistant to the majority of commonly used antibiotics. Antibiotic resistance levels and AMP-C production can be factors, indicating the better effectiveness of the graphene oxide and silver nanoparticle hybrid nanocomposite. Conclusions: In this study, a GO–Ag hybrid nanocomposite was shown to have the potential to fight even the most problematic bacteria like A. baumannii. Full article

Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment. Full article

Background and aim: Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients.
Materials and methods: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immu- nofixation to test for the presence of intrathecal specific OCB.
Results: HLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present.
Conclusions: OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS. Full article

The aim of the present study was to investigate the influence of HLA-DRB1 alleles on the genetic susceptibility to multiple sclerosis in the Lithuanian population.
Material and Methods. A total of 120 patients with multiple sclerosis and 120 unrelated healthy controls were enrolled in this case-control study. Allelic frequencies were compared between the groups. HLA-DRB1 alleles were genotyped using the polymerase chain reaction.
Results. HLA-DRB1*15 was present in 55.8% of the patients with multiple sclerosis and 10.0% of the controls (OR, 5.58; 95% CI, 3.19–9.77; P<0.0001). The protective alleles that were found to be more prevalent among the controls compared with the patients with multiple sclerosis were HLADRB1* 01 (26.7% vs. 7.5%, P<0.0001), *03 (17.5% vs. 8.3%, P=0.034), and *16 (11.7% vs. 3.3%, P=0.014). HLA-DRB1*15 was more common among the female patients with multiple sclerosis than among the male patients (68.4% vs. 34.1%; OR, 4.18; 95%, CI 1.90–9.22; P=0.001). The heterozygous inheritance of HLA-DRB1*15 allele was more common in the patients with a history of maternal multiple sclerosis than in those with a history of paternal multiple sclerosis (29.4% vs. 9.8%; P=0.045).
Conclusions. HLA-DRB1*15 was found to be associated with multiple sclerosis in the Lithuanian population. This allele was more prevalent among the female patients with multiple sclerosis. Maternal multiple sclerosis was more common than paternal multiple sclerosis, but the relationship with HLA-DRB1*15 allele was not established. HLA-DRB1*01, *03, and *16 appeared to be the protective alleles in this series. Full article

The aim of this study was to determine the characteristics of carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains and 5-year changes in resistance in a tertiary university hospital.
Material and Methods. The study included 90 and 101 randomly selected P. aeruginosa strains serotyped in 2003 and 2008, respectively. The standardized disk diffusion test and E-test were used to determine resistance to antibiotics. P. aeruginosa strains were considered to have high-level resistance if a minimum inhibitory concentration (MIC) for imipenem or meropenem was >32 μg/mL. To identify serogroups, sera containing specific antibodies against O group antigens of P. aeruginosa were used. P. aeruginosa isolates resistant to imipenem or/and meropenem were screened for metallo-β-lactamase (MBL) production by using the MBL E-test.
Results. Comparison of the changes in resistance of P. aeruginosa strains to carbapenems within the 5-year period revealed that the level of resistance to imipenem increased. In 2003, 53.3% of P. aeruginosa strains were found to be highly resistant to imipenem, while in 2008, this percentage increased to 87.8% (P=0.01). The prevalence of MBL-producing strains increased from 15.8% in 2003 to 61.9% in 2008 (P<0.001). In 2003 and 2008, carbapenem-resistant P. aeruginosa strains were more often resistant to ciprofloxacin and gentamicin than carbapenem-sensitive strains. In 2008, carbapenem- resistant strains additionally were more often resistant to ceftazidime, cefepime, aztreonam, piperacillin, and amikacin than carbapenem-sensitive strains. MBL-producing P. aeruginosa strains belonged more often to the O:11 serogroup than MBL-non-producing strains (51.7% vs. 34.3%, P<0.05). A greater percentage of non-MBL-producing strains had low MICs against ciprofloxacin and amikacin as compared with MBL-producing strains.
Conclusions. The results of our study emphasize the need to restrict the spread of O:11 serogroup P. aeruginosa strains and usage of carbapenems to treat infections with P. aeruginosa in the intensive care units of our hospital Full article

The aim of the present study was to determine the value of immunogenetic risk factors and to estimate their relationship with the clinical features and disability status of patients with multiple sclerosis in a Lithuanian population.
Materials and Methods. This was a prospective study of 80 patients with multiple sclerosis. The diagnosis of multiple sclerosis was based on the revised McDonald criteria. Oligoclonal bands (OCBs) of immunoglobulin G (IgG) were tested using isoelectric focusing and IgG specific immunofixation. HLA DRB1 alleles were genotyped using polymerase chain reaction.
Results. Of all patients, 55% were positive for OCBs and 56% for HLA DRB1*1501. OCBpositive patients with multiple sclerosis had higher EDSS scores than their OCB-negative counterparts at onset of the disease (3.93±1.21 and 3.36±0.96 points, respectively; P=0.02) and during the last visit (4.31±2.06 and 3.09±1.98 points, respectively; P=0.009). The mean relapse rate was higher in the OCB-positive group compared with OCB-negative group (1.45±0.69 and 0.58±0.64, respectively; P=0.001). OCB-positive patients had higher IgG index compared with OCB-negative patients (P=0.0001). No relationship was found between HLA DRB1*1501 antigen status and the clinical features or EDSS score, and presence or absence of OCB in the present subset of patients with multiple sclerosis.
Conclusions. The presence of oligoclonal bands in the cerebrospinal fluid of the patients with multiple sclerosis was associated with the greater number of exacerbations, higher degree of disability, and higher IgG index. There were no significant associations between the presence of HLA DRB1*1501 allele and the clinical symptoms, course of disease, or disability score. Full article

The aim of our study was to determine the changes in antibiotic resistance and O serogroup dependence of P. aeruginosa strains isolated from lower respiratory tract specimens of patients in 2003 and 2008; the patients were treated in intensive care units of the biggest treatment facility in Lithuania (Hospital of Lithuanian University of Health Sciences, HLUHS, former Hospital of Kaunas University of Medicine)
Material and Methods. The study included 90 P. aeruginosa strains serotyped in 2003 and 101 P. aeruginosa strains serotyped in 2008, which were randomly selected. The resistance of P. aeruginosa strains was determined by the disc diffusion method based on the standard guidelines. The sizes of inhibition zones were interpreted according to the National Committee for Clinical Laboratory Standards (M2-A6). Isolates were serotyped using sera with specific antibodies against the O antigens of P. aeruginosa (Bio-Rad, France).
Results. Comparison of changes in the distribution of P. aeruginosa serogroups in 2003 and 2008 showed that P. aeruginosa strains of serogroups O:1, O:2, and O:3 were more prevalent in 2003 as compared with 2008 (23.3%, n=21; 27.8%, n=25; 12.2%, n=11 vs. 9.9%, n=10; 10.9%, n=11; 4.0%, n=4, P<0.05). P. aeruginosa strains of serogroups O:6 and O:11 were isolated more frequently in 2008 than 2003 (26.7%, n=27; 34.7%, n=35 vs. 4.4%, n=4; 10.0%, n=9, P<0.001). The results showed that 18 of the 90 P. aeruginosa strains in 2003 and 25 of the 101 P. aeruginosa strains in 2008 were resistant to three or more antibiotics tested, i.e., they were multidrug-resistant. Analysis of the distribution of serogroups among these P. aeruginosa strains isolated in 2003 and 2008 revealed a significantly higher frequency of O:11 serogroup than other serogroups. Meanwhile, in the group of nonmultidrug-resistant P. aeruginosa strains, P. aeruginosa O:11 serogroup strains were identified less frequently and accounted only for 2.8% (n=2, P<0.001) of the isolates in 2003 and 27.6% (n=21, P<0.01) in 2008.
Conclusions. During the 5-year period, the isolation rate of P. aeruginosa strains belonging to serogroup O:11 increased. P. aeruginosa strains isolated in 2003 and 2008 belonging to serogroup O:11 were more frequently multidrug resistant. The increasing resistance of P. aeruginosa to reserve antibiotics of carbapenem group was observed. Full article

The aim was to estimate changes in the resistance rates of Pseudomonas aeruginosa (P. aeruginosa) strains isolated from patients treated in intensive care units of the largest university hospital.
Materials and Methods. Isolates were identified with the Phoenix ID system (Becton Dickinson, USA). The minimum inhibitory concentration (MIC) of ceftazidime, ciprofloxacin, and amikacin were determined by the E-test and evaluated following the recommendations of the Clinical Laboratory Standards Institute.
Results. In 2003, the proportion of P. aeruginosa strains resistant to piperacillin was greatest followed by strains resistant gentamicin and ciprofloxacin. In 2008, the resistance rates markedly changed being the highest to ciprofloxacin. An increase in the resistance rates to ciprofloxacin (+24%, P<0.001) and ceftazidime (+8.3%, P<0.05) was documented. In 2003, there were 66.7% of P. aeruginosa strains sensitive to all antibiotics tested, and this percentage decreased to 47.5% in 2008 (P<0.05). During the study, a significant increase in the median MICs for ciprofloxacin and amikacin was observed (P<0.001); however, no significant change was documented for ceftazidime.
Conclusions. P. aeruginosa remains an important nosocomial pathogen with relatively high overall resistance to antimicrobial agents, and the resistance level is increasing. Full article

Objective. Type 1 diabetes mellitus is a slowly progressive autoimmune disease. The genetic background of type 1 diabetes mellitus is polygenic with the major disease locus located in the human leukocytes antigen (HLA) region. High risk and protective alleles, haplotypes, and genotypes have been determined in Lithuanian children with type 1 diabetes mellitus and healthy children.
Material and methods. In this case-control study, 124 children with diabetes (55 males and 69 females; mean age, 9.2±3.9 years) were tested for HLA class II and compared with 78 healthy controls (43 males and 35 females; mean age, 10.8±3.4 years; range, 0–15 years). HLA DRB1, DQA1, and DQB1 alleles were genotyped using a polymerase chain reaction.
Results. T1D risk-associated haplotypes (DR4)-DQA1*0301-DQB1*0302, (DR3)- DQA1*0501-DQB1*0201, and (DR1)-DQA1*0101-04-DQB1*0501 were more prevalent among children with diabetes than controls (50.0%, 41.1%, and 37.9% vs. 10.3%, 5.1%, and 24.4%, P<0.001). The haplotypes (DR4)-DQA1*0301-DQB1*0302 and (DR3)-DQA1*0501-DQB1*0201 increased T1D risk by 8.75 and 12.93 times, respectively (P<0.001). Protective haplotypes (DR2)- DQA1*0102-B1*0602, (DR11/12/13)-DQA1*05-DQB1*0301, and (DR13)-DQA1*0103- DQB1*0603 were significantly more prevalent among controls than children with diabetes (25.6%, 33.3%, 19.2% vs. 0%, 3.2%, 0%; P<0.001). These frequencies are quite similar to those from neighbor countries with varying incidence of type 1 diabetes mellitus.
Conclusions. HLA class II haplotypes associated with type 1 diabetes mellitus positively or negatively were the same in Lithuanian children as in other European Caucasian populations. Differences in incidence and clinical manifestations of type 1 diabetes might be due to different environmental factors and/or lifestyle. Full article

The aim of our study was to determine the prevalence of Pseudomonas aeruginosa bacteremia, risk factors, and outcome of patients treated at the Hospital of Kaunas University of Medicine.
Material and methods. All hospitalized patients with blood culture positive for Pseudomonas aeruginosa during the 5-year period were included. A retrospective data analysis was performed to evaluate patients’ risk factors and mortality caused by P. aeruginosa bacteremia.
Results. A total of 47 (58.8%) bacteremia episodes occurred in an intensive care unit (ICU). A primary source of bacteremia was identified in 50 (62.5%) episodes. Overall mortality rate was 58.8%. Univariate risk factors analysis showed the factors, which significantly increased the risk of death: mechanical ventilation (13.67 times, P<0.001), patient hospitalization in the ICU (8.51 times, P<0.001), acute respiratory failure (8.44 times, P<0.001), infection site in the respiratory tract (4.93 times, P=0.003), and central vein catheter (4.44 times, P=0.002). Timely and appropriate treatment and surgery were significant protective factors for 30-day mortality (11.1 and 5.26 times, respectively; P=0.001). Meropenem-resistant Pseudomonas aeruginosa strains caused bacteremia more frequently in patients older than 65 years than meropenem-sensitive strains (57.9%, n=11). All 19 patients with meropenem-resistant Pseudomonas aeruginosa bacteremia received inappropriate empirical antibiotic therapy.
Conclusions. Treatment at the intensive care unit, mechanical ventilation, acute respiratory failure, source of infection in respiratory tract, and central vein catheter are the major risk factors associated with an increased mortality rate in patients with Pseudomonas aeruginosa bacteremia. The patients older than 65 years are at increased risk for bacteremia caused by carbapenemresistant Pseudomonas aeruginosa strains. Carbapenems are not antibiotics of the choice of treatment for Pseudomonas aeruginosa bacteremia at the Hospital of Kaunas University of Medicine. Full article

Tyrimo tikslas. Nustatyti pažeistų nagų onichomikozės dažnumą sergantiesiems žvy neline ir šia liga nesergantiems tiriamiesiems.
Medžiaga ir metodai. Į tyrimą įtraukti 559 pacientai (168 vyrai ir 391 moteris) tirti dėl nagų grybinės infekcijos, jiems atlikta mikroskopija ir pasėlis.
Rezultatai. Žvyneline sirgo 30/559 (5,3 proc.) tiriamųjų (9 vyrai ir 21 moteris). Onichomikozės dažnumas (pagal teigiamus pasėlio rezultatus) tarp sergančiųjų žvyneline buvo 7/30 (23,3 proc.) palyginus su 125/529 (23,6 proc.) žvyneline nesergančiais tiriamaisiais (p>0,05). Iš septynių teigiamų pasėlių penkiems (71,4 proc.) sergantiesiems žvyneline išskirti dermatofitai, po vieną atvejį – mielės arba į mieles panašūs grybai. Iš 125 teigiamų pasėlių nesergantiesiems žvyneline išskirti dermatofitai, mielės ir pelėsiai, atitinkamai – 66, 43, ir 16 atvejų. Mikroskopinio tyrimo jautrumas, lyginant su pasėliu, dermatofitams yra 87,3 proc., mielėms atitinkamai – 18,6 proc.
Išvados. Onichomikozės dažnumas ir grybo rūšių pasiskirstymas pažeistuose naguose tarp sergančiųjų žvyneline ir šia liga nesergančių tiriamųjų nesiskiria. Onichomikozė nustatyta mažiau nei trečdaliui pacientų, kurie turėjo pažeistus nagus. Pasėlio metodas yra svarbus diagnozuojant onichomikozę ir parenkant sisteminį gydymą. Full article

Objective. The damage of beta cells occurs during the asymptomatic prodromal period called prediabetes before onset of diabetes mellitus. It is characterized by the presence of islet cell autoantibodies (ICAs). The aim of this study was to find out what environmental factors predict ICA seroconversion in healthy schoolchildren in Lithuania.
Material and methods. Sera from 3053 nondiabetic schoolchildren living in Lithuania were investigated for ICAs. ICAs were measured in undiluted sera by indirect immunofluorescence method. All ICA-positive and randomly selected ICA-negative children were invited to participate in the study. Response rate in the families of ICA-positive children was 100% and in ICA-negative – 76.5%. Data from 13 ICA-positive and 199 ICA-negative schoolchildren were included in the analysis. Information on the environmental factors was collected via questionnaires.
Results. Proportions of breastfed children were similar in ICA-positive and ICA-negative schoolchildren. Full cow’s milk was introduced at one month of age or earlier more often in ICApositive than ICA-negative schoolchildren (8.3% and 1.1%, respectively; P=0.05). Cereal before 3 months of age was introduced more often in ICA-positive than ICA-negative schoolchildren (7.7% and 0.5%, respectively; P=0.01). The mothers of cases took medicine during pregnancy more often than mothers of controls did (61.5% and 14.1%, respectively; P<0.001). More than half (53.8%) of ICA-positive children lived in homes where family members were smoking indoors, while this was recorded only for 26.6% of controls (P=0.04).
Conclusions. Early introduction of cow’s milk and cereal, the intake of medicine during pregnancy, and indoor smoking of family members are risk factors that predict the development of prediabetes among Lithuanian children. Full article