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Background and Objectives : PoCUS ultrasound applications are widely used in everyday work, especially in the field of emergency medicine. The main goal of this research was to create a diagnostic and therapeutic protocol that will integrate ultrasound examination of the lungs, ultrasound measurements of the inferior vena cava (assessment of central venous pressure) and BREST scores (risk stratification for heart failure), with the aim of establishing a more effective differential diagnostic approach for dyspneic patients. Materials and Methods: A cross-sectional study was conducted in the emergency medicine department with the educational center of the community health center of Banja Luka. Eighty patients of both sexes were included and divided into experimental and control groups based on the presence or absence of dyspnea as a dominant subjective complaint. Based on the abovementioned variables, the LUSBI protocol (lung ultrasound/BREST score/inferior vena cava) was created, including profiles to determine the nature of the origin of complaints. The biochemical marker of heart failure NT pro-BNP served as a laboratory confirmation of the cardiac origin of the complaints. Results : The distribution of NT pro BNP values in the experimental group showed statistically significant differences between individual profiles of the LUSBI protocol ( p < 0.001). Patients assigned to group B PLAPS 2 had significantly higher average values of NT pro-BNP (20159.00 ± 3114.02 pg/mL) compared to other LUSBI profiles. Patients from the experimental group who had a high risk of heart failure according to their BREST scores also had a significantly higher average maximum expiratory diameter compared to those without heart failure ( p = 0.004). A statistically significant difference ( p = 0.001) in LUSBI profiles was observed between the groups of patients divided according to CVP categories. Conclusion : The integration of the LUSBI protocol into the differential diagnosis of dyspnea has been shown to be very effective in confirming or excluding a cardiac cause of the disease in patients.

The aim of this study is to propose a test method for the determination of the quality of transformer paper insulation. For this purpose, the oil/cellulose insulation systems were exposed to various accelerated aging tests. The results of the aging experiments of normal Kraft and thermally upgraded papers, two different types of transformer oil (mineral and natural ester), and copper are shown. Aging was carried out in various experiments at 150 °C, 160 °C, 170 °C, and 180 °C with dry (initial values ≤ 0.5%) and moistened cellulose insulation (initial values 3-3.5%). Following insulating oil and paper, degradation markers were measured: the degree of polymerization, tensile strength, furan derivates, methanol/ethanol, acidity, interfacial tension, and dissipation factor. It was found that the aging of cellulose insulation in cycles was 1.5-1.6 times faster in comparison to continuous aging, due to the more pronounced effect of hydrolytic mechanism in cyclic aging owing to the produced and absorbed water. Furthermore, it was observed that the high initial water content in cellulose increases the aging rate two to three times more than in the dry experimental setup. The proposed aging test in cycles can be used to achieve faster aging and to compare the quality of different insulating papers.

The intestinal microbiota consists of trillions of bacteria, viruses, and fungi that achieve a perfect symbiosis with the host. They perform immunological, metabolic, and endocrine functions in the body. The microbiota is formed intrauterine. Dysbiosis is a microbiome disorder characterized by an imbalance in the composition of the microbiota, as well as changes in their functional and metabolic activities. The causes of dysbiosis include improper nutrition in pregnant women, hormone therapy, the use of drugs, especially antibiotics, and a lack of exposure to the mother's vaginal microbiota during natural birth. Changes in the intestinal microbiota are increasingly being identified in various diseases, starting in the early neonatal period into the adult period. Conclusions: In recent years, it has become more and more obvious that the components of the intestinal microbiota are crucial for the proper development of the immune system, and its disruption leads to disease.

COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Honeybees forage a large spatial area around the hives. In addition, honey production takes place in various environments, and polluted environment is often hard to detect. It impacts both human and beehive health, especially through honey which is used for human consumption. Pollen analysis was conducted by a novel approach through a multivariate principal component analysis where it was possible to obtain grouping patterns related to foraging plant species. Samples of honey were acquired from three different environmental production systems: (i) honey from the apiaries in the vicinity of thermal power plant, (ii) apiary of certified organic production and (iii) the conventional production with semi-controlled production. Significantly higher contents of the Pb, Cd and Zn are found in the analysed honeys taken near the thermal power plant compared with those of the other analysed honeys. The origin of Zn, Pb and Cd in the honey is the contaminated forage plants and foraging honeybees. Honey from certified organic production differentiated significantly from other two types of production by the water content, electrical conductivity and total soluble solids and notably it contained significantly less ash and lead. There is a clear advantage of certified organic honey in terms of heavy metal residues as the most prominent pollution factor in honey. Therefore, honey can be used as the broad range environmental pollution indicator, as bees will forage on polluted plants and bring the pollutant from a wide spatial range inside the hive, where it can be traced in the honey. Graphical abstract.

The aim of our study was to compare usefulness of endothelial biomarkers for severity and outcome prediction in patients with positive Sepsis-3 criteria with traditionally used biomarkers. A total of 150 patients were included in our study. Patients were divided into two groups: patients with sepsis and those with infectious systemic inflammatory response syndrome. Development of septic shock and 28-day mortality were assessed. Endocan and thrombomodulin showed better discriminative power than procalcitonin for the presence of sepsis. Endocan showed good discriminative power for septic shock prediction. Addition of endocan significantly contributed to sequential (sepsis-related) organ failure assessment score in logistic regression model. Conclusion: Endothelial biomarkers have a good diagnostic potential for sepsis. Endocan is useful as a predictor of the severity and fatality of sepsis.

Introduction: The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis., Methods: One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05., Results: A significant depletion of the complement was observed in non-survivors (AUCROC C3  = 0.692, p C3  < 0.001,AUCROC C4  = 0.672, p C4  = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients., Conclusion: In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

: Sepsis is associated with complex procoagulant and anticoagulant changes that modify inflammatory response. Identification of coagulation markers that can differentiate useful procoagulant response from adverse alteration of clotting mechanism in patient with sepsis. In total, 150 patients who fulfilled criteria for diagnosis of sepsis were included in this study. Patients were categorized in two groups according to sepsis severity in the first 24 h from intensive care unit admission: sepsis and septic shock. In total, 28-day mortality was assessed. Platelet count, activated partial thromboplastin time, prothrombin time, D-dimer, fibrinogen, protein C, protein S, antithrombin levels, and endogenous thrombin potential were determined within first 24 h from ICU admission. Differences between groups of septic patients were assessed by Mann-Whitney U test. Categorical variables were compared using χ test. Receiver operating characteristic curves were plotted to determine predictive values of variables for sepsis severity prediction. Activated partial thromboplastin time and prothrombin time were significantly prolonged with higher D-dimer, lower fibrinogen, and natural anticoagulant levels (protein C, protein S, and antithrombin) in patients with more severe form of the disease and worse outcome (P < 0.05). Endogenous thrombin potential [area under the curve (AUC) %] was significantly decreased in patients with more severe form of sepsis (66.01 ± 41.51 vs. 83.21 ± 28.83; AUC 0.76) and in patients with worse outcome (67.66 ± 37.79 vs. 81.79 ± 32.15; AUC 0.68; P < 0.05). Evaluation of initial thrombin generation is useful to distinguish between beneficial coagulation activation and hazardous haemostatic alteration, and to predict multiorgan dysfunction development and poor outcome in septic patients.

Published data indicate the involvement of eosinophil granulocytes and eosinophil cationic protein (ECP) in tumor defense. The aim of this study was to analyze serum ECP concentrations in patients with differentiated thyroid cancer (DTC) before, 3 days and 7 days after radioactive iodine (131-I) therapy. Association of ECP concentrations with histological type of tumor, stage of disease and/or levels of selected T-helper 2 (Th2) cytokines was examined. The study population included 17 DTC patients and 10 control subjects. ECP was measured by fluoroimmunoassay (FIA). Th2 (cytokines interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13)) were determined by enzyme-linked immunosorbent assays (ELISA). We found that ECP values in DTC patients before radioactive iodine therapy were approximately two-fold higher than in the controls, but the difference was statistically significant only if the patients with DTC and associated Hashimoto thyroiditis (HT) were included. There was no correlation between the serum concentrations of IL-5 and ECP. Radioactive iodine therapy led to a decrease in serum ECP level which did not follow the decline in serum protein levels. Additional studies are needed to determine the significance of these findings., (© 2017 by the Association of Clinical Scientists, Inc.)

Purpose: There is a need for identification of marker that could lead physicians to take the right step towards laboratory techniques for documentation of infection. The aim of this study was to investigate whether presepsin and procalcitonin (PCT) levels in patients with suspected sepsis could predict blood culture (BC) and SeptiFast (SF) results., Material and Methods: 100 patients were included in our study. PCT, C-reactive protein (CRP), and presepsin levels were determined. Differences between groups of patients were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test. Receiver operating characteristic (ROC) curves were plotted to determine predictive values of biomarkers for prediction of positive SF results., Results: PCT (70.9±106.36 vs. 16.35±26.79) and presepsin (4899.73±5207.81 vs. 1751.59±2830.62) were significantly higher in patients with positive SF in contrast to patients with negative SF. There was no significant difference between patients who had positive and negative BC for PCT and presepsin values. PCT and presepsin showed a similar performance in predicting positive SF results with AUC of 0.75 for PCT and 0.73 for presepsin., Conclusion: Presepsin can serve as good predictor of bacteremia detected by SF and it should be included with PCT in protocols for sepsis diagnosing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was the evaluation of 15 days dietary regimen of depurinized (DP) milk (obtained using our patented technological procedures) or 1.5% fat UHT milk instead of standard chow diet, on rat thymus and bone marrow MyD88/Akt/p38, NF-κB, caspase-1 and endonuclease pathways, in relation to peripheral blood cell composition. To determine whether the reduced mass of the thymus is a consequence of the direct effect of DP/UHT milk on apoptosis of thymocytes, in vitro Annexin-V-FITC/PI assay was performed. Significant decreases in the thymus wet weight, thymocyte MyD88, Akt-1/phospho-Akt-1 kinase, p38/phospho-p38, NF-κB, caspase-1 activity and CD4+/CD8+ antigen expression were obtained, especially in the DP milk group. The activity of thymocyte alkaline and acid DNase increased in the DP but not in the UHT milk group. The level of IL-6 significantly decreased in DP milk treated group, while the level of total TGF-β and IL-6 increased in UHT milk group. Significant differences in hematological parameters were obtained in commercial milk fed group. Observed results about prevention of experimental diabetes in DP pretreated groups may suggest that purine compounds, uric acid and other volatile toxic compounds of commercial milk may suppress oral tolerance, probably via IL-6 and TGF-β cytokine effects., Competing Interests: The authors declare no competing financial interests.

Dear Editor, Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease. The primary clinical presentation are painful inflamed nodules or boils of inverse areas, i.e. the axillary and anogenito-crural regions, but it can also involve the infra- and inter-mammary regions (1,2). The etiology of HS is not clearly defined. Obesity, smoking, and genetic factors are considered important risk factors. In addition, it has also been suggested that friction may contribute to the development of HS, especially in the obese, but this is based on highly anecdotal reports (3-5). We describe a case with classic HS, obesity, and HS-like lesions at the position of the bra strap, suggesting that mechanical stress was an external pathogenic factor for HS development. A 33-year old woman presented with an 18-year history of chronic, recurrent, inflammatory nodules in the axillae, the groin, the pubic region, and to a lesser extent the abdomen and buttocks. She was obese with as result of 33.2 kg/m-2 of 33.2, had a positive family history of two first grade family members with HS, and was a smoker (19 Pack years). There were no other known comorbidities. The inflamed lesions had been treated with several courses of oral antibiotics (minocycline, erythromycin, and combination therapy of clindamycin and rifampicine) and surgical treatments: lancing, deroofing, and excisions (2,6). On examination, there were nodules, folliculitis, cysts, and depressed scars in the axillae and groins, including the inner thighs (Figure 1). On the chest, corresponding to where the lower edge of the patient's bra was usually located, a superficial nodule and follicular papules were observed, exactly coinciding with the red stripe caused by mechanical stress (friction and pressure) of the bra edge. There was no skin fold present on the location of the HS lesions, and there were no lesions observed in the intermammary region or on the side of the breasts in contact with the skin of the thorax (skin to skin contact) (Figure 2). Cultures from skin swabs showed commensal skin flora and moderate mixed anaerobic bacteria, as would be expected in a HS lesion. It is well documented that HS is a disease of the obese. However, the role of friction as an environmental factor is poorly documented. Patients report that environmental factors such as tight-fitting clothing or friction could cause flares in the disease (2). Furthermore, it has been postulated that friction may contribute to the development of HS by stimulating interfollicular hyperplasia (7). HS lesions arranged in a linear pattern suggest an environmental influence and suggests an etiopathogenic role for mechanical stress. Waistline, or as in this case the chest line, distribution indicates that wearing of tight waistbands, wide belts, or bras may induce HS in predisposed individuals. To our knowledge, there is only one case report describing an obese patient with classic HS (typical lesions in predilection areas) who developed HS like lesions on the upper abdomen (waist) at the height of the waistband as well as under the lower abdominal apron (skin on skin contact) (8). Two other reports suggesting a pathogenic role for mechanical stress are flawed, however, as neither of the cases showed signs of concomitant classic HS or had a family history, bringing into question the implied association of HS (9,10). In summary, we presented a case with classic HS locations (typical lesions on typical locations, i.e. the axillae and inguino-crural regions) developing inflammatory lesions on the chest at the location closely corresponding to where the bra strap was exerting mechanical pressure and friction on the skin. The lesions were clinically and microbiologically compatible with ectopic HS lesions. The chest is an atypical HS location free of apocrine sweat glands. It is postulated that these lesions may have been induced by mechanical stress, additionally triggered by the pro-inflammatory state of the obese body. Patients are encouraged to avoid friction from environmental factors such as tight clothing.

Transforming growth factor beta (TGF-β) plays an important role in many pathophysiological conditions, including cancer. The level of TGF-β in patients with differentiated thyroid cancer (DTC) has not been examined so far. The aim of this study was to measure TGF-β concentration in serum samples and in PHA-stimulated whole blood culture in vitro and to analyze possible associations of TGF-β1 levels with leukocyte, lymphocyte and platelets counts, the histological type of thyroid cancer, and stage of disease. TGF-β1 was measured in 22 DTC patients and 20 healthy controls using the duoSet ELISA Development kit for human TGF-β1. The concentration of TGF-β1 in serum samples from both groups correlated positively with the platelet counts. There was no statistically significant difference in the serum concentrations of TGF-β1 between DTC patients and control subjects, but PHA stimulated whole blood cultures of DTC patients produced less TGF-β1 than those from controls. Additional studies are needed to determine the significance of these in vitro findings., (© 2016 by the Association of Clinical Scientists, Inc.)

Purpose: The purpose of this study is to give an overview of studies investigating the role of fludeoxyglucose F18 ((18)F-FDG) positron emission tomography (PET) scanning in patients with aortic aneurysms with a focus on molecular characteristics of the aneurysm wall., Methods: MEDLINE, EMBASE, and the Cochrane database were searched for relevant articles. After inclusion and exclusion, we selected 18 relevant articles reporting on (18)F-FDG PET scanning of aortic aneurysms., Results: The sample size of studies is limited, and there are no standardized imaging protocols and quantification methods. (18)F-FDG PET scanning was shown to display molecular characteristics of the aortic wall. Different studies showed contradictory findings of aortic (18)F-FDG uptake in aneurysm patients compared to controls., Conclusions: Non-invasively determining molecular characteristics of aortic wall weakening might lead to better rupture and growth prediction. This might influence the decision of the surgeon between conservative and surgical treatment of aneurysms. To date, there is conflicted evidence regarding the use of (18)F-FDG PET scanning to predict aneurysm rupture and growth. The role of (18)F-FDG PET scanning in rupture risk prediction needs to be further investigated, and standardized imaging protocols and quantification methods need to be implemented.

Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); Th9-interleukin 9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity.

Background/aim: Clinical manifestations of sepsis are not caused directly by the invading pathogens, but rather mostly by systemic inflammation that leads to activation of the coagulation system. The aim of this study was to determine whether levels of hemostasis- related parameters measured in intensive care unit admissions are associated with mortality and severity in patients with sepsis., Materials and Methods: Eighty-five patients who fulfilled criteria for a diagnosis of sepsis were included in our study. Platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time, D-dimer, and fibrinogen levels were determined within the first 24 h from sepsis onset. Differences between groups of septic patients were assessed by Mann-Whitney U test and Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors., Results: Prolonged aPTT and PT with higher D-dimer concentrations in patients with sepsis are associated with more severe forms of the disease, aPTT was prolonged in nonsurvivors, while platelet count and fibrinogen levels were higher in survivors. Platelet count and aPTT ratio are independent predictors of fatal outcome in our logistic regression model., Conclusion: Hemostasis-related parameters have a significant impact on severity and outcome in sepsis.

Augmenting the nasal dorsum is often a difficult task, because of the irregularities that might be visible under the thin dorsal nasal skin. Saddle noses are especially difficult to correct because of the need to provide strong structural support to the nose while at the same time achieving an aesthetic dorsum. Stable reconstruction of the cartilaginous septum is the critical challenge in the operative treatment of such deformities with both functional and morphological implications. Treatment depends on the degree of saddling. Autologous cartilage is widely recognized to be the standard against which other materials must be judged. It is the most acceptable and reliable long-term graft. We present a case of unusually severe posttraumatic saddle nose resolved with a single rather large costal cartilaginous graft and a columellar strut. Classic extended spreader grafts could not be used due to the lack of bony and cartilaginous support of the nasal pyramid and, thus, no possibility of stabilization. A normal nasal dorsum, as well as breathing improvement, were achieved and the patient was extremely satisfied with the result. We had no complications except a slight asymmetry of the nostrils. Graft resorbtion or displacement was not observed on the 14-months follow-up., (Celsius.)

Purpose: The quantitative real-time polymerase chain reaction (qRT-PCR) is used in the detection of molecular events involved in leukemogenesis, such as the Bcr-Abl gene translocation, the most important factor in the pathogenesis of chronic myeloid leukaemia (CML). The main aim of our study was to test the reproducibility, specificity and sensitivity of the qRT-PCR in the detection of Bcr-Abl gene translocation., Methods: In complementary (c)DNA, isolated from K562 Bcr-Abl positive cell line, we performed qRT-PCR analysis with Bcr-Abl specific primers. For qRT-PCR analysis, we used serial dilutions of the newly synthesized cDNA in order to establish the detection threshold of this method., Results: Using the specific primers for the Bcr-Abl translocation, we obtained the specific translocation product in cDNA sample of K562 human erythroid leukemia cell line. qRT- PCR showed significant sensitivity with the detection threshold for the Bcr-Abl fluorescent signal, which enabled the precise detection that was accurate within a 10-fold dilution range, and a dynamic range of 5 orders of magnitude., Conclusion: The results of our study showed that the application of the qRT-PCR is the optimal method for the detection of Bcr-Abl gene translocation, characterized by high reproducibility, specificity and sensitivity.

Background: Malignant melanoma (MM) is an extremely malignant tumor with an unpredictable profile of spread and variable periods of remission., Case: We describe an unusual case of malignant melanoma metastatic to the omentum occurring seven years after diagnosis and treatment of cutaneous malignant melanoma in the patient's arm. She received surgery and chemoimmunotherapy. To date, nine months after detection of malignant melanoma metastatic to the omentum, the patient is alive with no clinical and radiological metastatic disease., Conclusions: The diagnosis of omentum malignant melanoma in a living patient is uncommon, thus very few individuals and referral centers can build up an adequate experience of handling this disease. Optimal management has been a challenge and a subject of debate and has not yet been established.

Objective: To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months., Methods: Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6-12 weeks from prior second-line therapy was required., Results: Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo. Twenty-one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10-mg and 25-mg dosage groups. The incidence of infections was similar between the treatment and placebo groups; no opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients., Conclusion: Leflunomide is effective in daily doses of 10 mg and 25 mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebo-controlled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.

1. In our short reference we have shown the complete number of injuries sustained through shooting and we have indicated their enormous frequencies which can be regarded to be equal to those injuries in traffic communication. 2. While treating the injuries of extremities, as war injuries using the same principals as in war, we have obtained the best results and lessened the possibility of complication. 3. In the above cases for osteosinthesis of long bones, we held the principles of prolonged osteosinthesis while the primary osteosinthesis were use in special cases.