Concurrent Elevations of VEGF, Osteopontin and MCP-1 Serum Levels Are Independent Predictors of Survival in Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCL) are heterogeneous diseases, and the identification of additional DLBCL risk factors is especially important. METHODS: In this pilot study, we determined pretreatment serum levels of vascular endothelial growth factor (VEGF), osteopontin (OPN) and macrophage chemotactic protein-1 (MCP-1) in 67 newly diagnosed DLBCL patients before treatment with standard chemoimmunotherapy and in 30 healthy persons. RESULTS: Serum levels of all three cytokines were significantly elevated in untreated patients compared to controls. VEGF and OPN concentrations were higher in patients with advanced Ann Arbor stage, B symptoms, Eastern Cooperative Oncology Group score ≥2, International Prognostic Index (IPI) ≥3 and partial/no remission. A high MCP-1 level was associated with advanced stage, increased IPI and bone marrow infiltration. In univariate analysis, elevated OPN and VEGF, and concurrent elevation of all three biomarkers, were identified as significant predictors of poor survival. Multivariate Cox analysis revealed that elevated OPN combined with elevated VEGF levels was one of the best parameter subsets predicting poorest survival. CONCLUSION: According to our preliminary results, serum levels of VEGF and OPN before treatment predict response to therapy and survival after chemoimmunotherapy, and may help to further stratify DLBCL patients into risk groups.

New classification criteria for systemic lupus erythematosus correlate with disease activity.

AIM: To determine the prevalence of American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) classification criteria among systemic lupus erythematosus (SLE) patients; to determine disease activity and severity; and to investigate the correlation of classification criteria with disease activity, and of disease activity and damage index with disease duration. METHODS: We performed a cross-sectional study on 110 SLE patients from the Division of Rheumatology and Clinical Immunology, University Hospital Centre Rijeka, Croatia in the period from September to December 2013 and determined disease duration and the total number of ACR and SLICC classification criteria. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) index and organ damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: The number of SLICC classification criteria met per patient was significantly higher than the number of ACR criteria (7 [IQR 6-8] vs 5 [IQR 4-6], P < 0.001). Moderate correlations were detected between the number of SLICC classification criteria and disease activity index, both in case of active (r=0.48, P=0.003) and inactive disease (r=0.43, P < 0.001). We neither found a correlation between the number of ACR criteria and disease activity nor between disease activity and disease duration. However, there was a good correlation between SLICC/ACR damage index and disease duration (r=0.63, P < 0.001). CONCLUSION: New SLICC classification criteria correlate with disease activity because they capture more manifestations also included in the SLEDAI index. Patients with longer disease duration had a larger damage index score.

Prognostic performance of the Simplified Acute Physiology Score II in major Croatian hospitals: a prospective multicenter study.

AIM: To perform an external validation of the original Simplified Acute Physiology Score II (SAPS II) system and to assess its performance in a selected group of patients in major Croatian hospitals. METHODS: A prospective, multicenter study was conducted in five university hospitals and one general hospital during a six-month period between November 1, 2007 and May 1, 2008. Standardized hospital mortality ratio (SMR) was calculated from the mean predicted mortality of all the 2756 patients and the actual mortality for the same group of patients. The validation of SAPS II was made using the area under receiver operating characteristic curve (AUC), 2×2 classification tables, and Hosmer-Lemeshow tests. RESULTS: The predicted mortality was as low as 14.6% due to a small proportion of medical patients and the SMR being 0.89 (95% confidence interval [CI], 0.78-0.98). The SAPS II system demonstrated a good discriminatory power as measured by the AUC (0.85; standard error [SE]=0.012; 95% CI=0.840-0.866; P<0.001). This system significantly overestimated the actual mortality (Hosmer-Lemeshow goodness-of-fit H statistic: χ(2) =584.4; P<0.001 and C statistics: χ(2)(8) =313.0; P<0.001) in the group of patients included in the study. CONCLUSION: The SAPS II had a good discrimination, but it significantly overestimated the observed mortality in comparison with the predicted mortality in this group of patients in Croatia. Therefore, caution is required when an evaluation is performed at the individual level.

Effect of preoperative feeding on gallbladder size and peristaltic of the small bowel following spinal anesthesia for the hip surgery.

The main aim of our study was to determine the influence of preoperative feeding with clear carbohydrate rich drink (PreOp 200 mL) on peristaltic of the small intestine and gallbladder size early after the orthopedic surgery in spinal anesthesia. Clinical study includes 120 patients with fracture of femoral neck or pertrochanteric fracture. All patients were randomized in two groups, sixty patients, PreOp group, consumed carbohydrate drink two hours before surgery. Other 60 patients, Control group, represent patients who fasted overnight. After surgery, patients were submitted to ultrasound examination for measurement of the small bowel motions and gallbladder size. Four quadrants (up-right, up-left, down-right and down-left) of the abdomen were examined, each one in duration of 30 seconds. The results show that the length of the gallbladder is considerably different across the two groups; 5.866 cm in the PreOp group and 7.178 cm in the Control group (p = 0.00). The width, however, differed somewhat less (PreOp group 2.437 cm, Control group 2.735 cm) and the statistically significant difference can be observed at 7% level (p = 0.073). We found no statistically significant relationship between PreOp and Control group variables of each abdominal quadrant (lowest p > 0.087). Accordingly, the means of the variables were found statistically significantly different between groups (p > 0.05). In conclusion our study showed that the preoperative feeding of the patients undergoing orthopedic surgery in spinal anesthesia shortens the length but not the width of the gallbladder when compared with overnight fasting patients and also clearly enhance motility of the small bowel in all four quadrant of the abdomen.

Presence of third molar germs in orthodontic patients with class II/2 and class III malocclusions.

The aim of this study was to determine the presence of third molar germs in patients with Class II/2 and Class III malocclusions. The study comprised 146 examinees from Zagreb and Istria. Examinees with Class II/2 malocclusions amounted to 77 and those with Class III 69. With regard to development of dentition the examinees were divided into two groups: Group I subjects with early mixed dentition (23 subjects with Class II/2 and 21 subjects with Class III), and Group II subjects with late mixed dentition (54 subjects with Class II/2 and 48 subjects with Class III). Assessments were made from panoramic radiographs and lateral cephalograms. The Pearson chi2-test and Fisher's exact test was used to determine statistical significance in differences. Assessments showed that third molar germs were present significantly more often in the upper jaw in Class II/2 (58% vs. 44%) and in the lower jaw in Class III (83% vs. 69%). In subjects with Class II/2 all third molar germs were present statistically more often in late mixed dentition, which was also determined for maxillary third molar germs in Class III. The presence of mandibular third molar germs in Class III examinees was almost equal in both periods of mixed dentitions. The study confirmed correlation between the presence of third molar germs and sagital maxillomandibular relationship and encourages investigation of the differences in calcifications of all permanent teeth in such malocclusions.

EPR study of lipid phase in renal cortical membrane organelles from intact and cadmium-intoxicated rats.

Numerous studies have demonstrated various structure/function correlations at the level of transport proteins in the kidney cell membranes and various intracellular organelles. However, characterization of the lipid phase of these membranes is rare. Here, we report the differences in lipid organization and dynamics of the brush-border membranes (BBM), basolateral membranes (BLM) and endocytotic vesicles (EV), isolated from the kidney cortex of intact rats, studied with the EPR spectroscopy of the spin-labeled membrane lipids. The EPR spectra were analyzed by comparing experimentally observed line shapes with the line shapes calculated according to the theoretical model developed for liquid crystals. In the fitting procedure, three different lipid domains were assumed, which revealed clear differences in the lipid ordering and rotational correlation times, as well as in the lipid partition of these domains in each of the three types of membranes. A similar approach, used to compare the spectroscopic characteristics of BBM from control and cadmium-intoxicated rats, showed significantly changed ordering and increased molecular mobility in the lipid phase of BBM from Cd-treated animals. As tested by an established fluorescence assay, the Cd-induced changes in the lipid mobility co localized with approximately 5-fold higher conductance of BBM for potassium, with unchanged conductance for protons.

[Characteristics of categorical data analysis]. / Osobitosti usporedbe nebrojcanih podataka.

This work presents characteristics of categorical data, their presentation and possible models of statistical analysis. There are two types of categorical data; nominal, where categories are equally valued (i.e. we can measure them only in terms of whether individual items belong to some distinctively different categories) and ordinal, where categories allow to rank order on some scale of measurement. Categorical data are non-numeric by nature, but could be numerically presented and analyzed anyway. Although the information value of categorical data is well below the respective information value of numerical, practically there's no study where their analysis wouldn't be of importance. Numerically, the categorical data can be presented via frequencies (absolute number of items belonging to the category) or their proportion (percentage) in the sample. Adequate graphical presentation goes with pie charts or percentage stacked bars charts. The statistical analysis of categorical data most often is done on contingency tables. The type of the analysis depends on the relation between samples from which the data are drowning. If the samples are independent, the analysis would be performed using difference of proportion test, chi2 test or Fisher exact test. The limitations and suitability for application of the three is discussed. If the samples are dependent, the choice goes to McNemar chi2 test (2 samples) or Cochrane's Q test 8more than 2 samples). The conclusions from the aforementioned analyses could be drowned only in terms of significant or nonsignificant relations between the rows and columns in the contingency tables. In the need to measure the level of relations between categorical data, two types of measures are defined: relative risk and odds ratio, which can both be calculated only in 2x2 contingency tables. Relative risk is a ratio of two proportions (suitable only in prospective studies), whether odds ratio measures ratio between odds in two groups (could be calculated both in prospective and retrospective studies). All the aforementioned analyses are well documented with calculations on data collected in biomedical studies.

Accuracy of targeted wire guided tube thoracostomy in comparison to classical surgical chest tube placement - A clinical study.

BACKGROUND: Chest tube malfunction, after the tube thoracostomy, is often the result of an inappropriate chest tube tip position. The aim of this study was to analyse the precision of chest tube placement using the targeted wire guide technique (TWG technique) with curve dilator and to compare it to the classical surgical technique (CS technique). MATERIALS AND METHODS: In this clinical study 80 patients with an indication for thoracic drainage, due to pneumothorax or pleural effusion were included. Experimental group contained 39 patients whose chest tube was placed using the TWG technique. The control group contained 41 patients whose chest tube was placed using the CS technique. RESULTS: The comparison of the outcomes of the two techniques applied suggests that the TWG technique was significantly more successful in achieving adequate (precise) chest tube placement, irrespective of patient diagnosis (TWG vs. CS in all patients, 78.4% vs. 36.6%, p<0.001). In the pleural effusion group, TWG and CS had success rates of 78.2% and 37.5% (p=0.005), respectively, while in pneumothorax group, TWG and CS had success rates of 78.6% and 35.3% (p=0.029), respectively. CONCLUSIONS: Using a curved dilator and the TWG technique for the thoracic drainage procedure we found statistically significant advantage to the TWG technique in comparison to the CS technique (78% vs. 37%) regarding precise chest tube placement within the pleural cavity. Introducing the materials and technique used in this clinical trial into clinical practice may improve the quality of thoracic drainage, including residual volume of air and/or fluid, poor functioning of the chest tube, and, as a consequence of both, prolonged hospitalisation.

Influence of the left ventricular types on QT intervals in hypertensive patients.

OBJECTIVE: To investigate the possible electrophysiological background of the greater excitability of concentric and eccentric left ventricular hypertrophy types in relation to the asymmetric type. METHODS: 187 patients with essential hypertension, without ishaemic heart disease were divided into three groups with regard to left ventricule type: concentric (relative wall thickness >0.42, interventricular septum/left ventricular posterior wall ≤1.3), eccentric (left ventricular diameter in systoles >32, relative wall thickness <0.42), asymmetric left ventricular hypertrophy (interventricular septum/left ventricular posterior wall >1.3), and three subgroups: mild (interventricular septum or left ventricular posterior wall 11-12 mm), moderate (interventricular septum or left ventricular posterior wall 13-14 mm) and severe left ventricular hypertrophy (interventricular septum or left ventricular posterior wall ≥15 mm). In all patients QT intervals, QT dispersion, left ventricular mass index and ventricular arrhythmias were measured. An upper normal limit for QT corrected interval: 450/460 ms for men/women; for QT dispersion: 70 ms. RESULTS: The QT corrected interval and QT dispersion were increased in severe concentric and eccentric left ventricular hypertrophy (443 and 480 ms for QT corrected; 53 and 45 ms for QT dispersion, respectively), not significantly. QT dispersion in men with severe left ventricular hypertrophy was significantly enlarged (67.5 vs. 30 ms, p=0.047). QT interval was significantly longer in patients with complex ventricular arrhythmias (p=0.037). CONCLUSION: No significant association of QT intervals or QT dispersion with the degree/type of left ventricular hypertrophy was found. QT corrected interval and QT dispersion tend to increase proportionally to the left ventricular mass only in the concentric and eccentric type.

The IVF Outcome Counseling Based on the Model Combining DHEAS and Age in Patients with Low AMH Prior to the First Cycle of GnRH Antagonist Protocol of Ovarian Stimulation.

Objective. To investigate the endocrine and/or clinical characteristics of women with low anti-Müllerian hormone (AMH) that could improve the accuracy of IVF outcome prediction based on the female age alone prior to the first GnRH antagonist IVF cycle. Methods. Medical records of 129 patients with low AMH level (<6.5 pmol/L) who underwent their first GnRH antagonist ovarian stimulation protocol for IVF/ICSI were retrospectively analyzed. The main outcome measure was the area under the ROC curve (AUC-ROC) for the models combining age and other potential predictive factors for the clinical pregnancy. Results. Clinical pregnancy rate (CPR) per initiated cycles was 11.6%. For the prediction of clinical pregnancy, DHEAS and age showed AUC-ROC of 0.726 (95%CI 0.641-0.801) and 0.662 (95%CI 0.573-0.743), respectively (P = 0.522). The predictive accuracy of the model combining age and DHEAS (AUC-ROC 0.796; 95%CI 0.716-0.862) was significantly higher compared to that of age alone (P = 0.013). In patients <37.5 years with DHEAS >5.7 pmol/L, 60% (9/15) of all pregnancies were achieved with CPR of 37.5%. Conclusions. DHEAS appears to be predictive for clinical pregnancy in younger women (<37.5 years) with low AMH after the first GnRH antagonist IVF cycle. Therefore, DHEAS-age model could refine the pretreatment counseling on pregnancy prospects following IVF.

The patterns of melanoma presentation in Rijeka region.

There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people.

Benefit of the minimal invasive ultrasound-guided single shot femoro-popliteal block for ankle surgery in comparison with spinal anesthesia.

BACKGROUND: Ultrasound-guided regional anesthesia has gained popularity for ankle and foot surgery. The aim of our study was to investigate the sufficiency of anesthesia for ankle surgery as well as duration of analgesia in postoperative period, using minimal invasive ultrasound-guided regional anesthesia, and to compare it with anesthesia and postoperative analgesia following spinal anesthesia. METHODS: This prospective study included 40 adult trauma patients with bimalleolar fracture who were scheduled for surgery. They were randomly assigned and divided in two groups. Patients from the first group underwent an Ultrasound-guided femoro-popliteal block (US-FPB), while a spinal anesthesia (SA) was performed for the second group. The local anesthetic 0.5% bupivacaine was used in both groups. RESULTS: Eighteen patients from the first and nineteen patients from the second group completed the study. Levels of anesthesia were sufficient in both groups without significant differences. Duration of postoperative analgesia was significantly higher in US-FPB group in comparison to SA group (12 ± 3 vs. 3 ± 1 h) (p < 0.001). At the same time, onset of complete sensory motor block was significantly faster in SA group in comparison to US-FPB group (5 ± 1 vs. 8 ± 3 min) (p < 0.001). CONCLUSION: Minimal invasive US-FPB provides sufficient anesthesia for ankle fracture. In comparison to the SA group, patients from the US-FPB group achieved significantly longer postoperative analgesia, while faster onset of anesthesia was noted in SA group.

Effect of preoperative feeding on gastric emptying following spinal anesthesia: a randomized controlled trial.

BACKGROUND: Preoperative fasting is associated with various untoward postoperative health problems. Previous studies have stressed the advantages of preoperative feeding with a carbohydrate-rich drink 2 hours before surgery; this protocol does not increase the risk of gastric-content aspiration but reduces the level of anxiety and thirstiness during the perioperative period. Spinal anesthesia with the local anesthetic bupivacaine can decrease gastric emptying in the early postoperative period. However, the effect of spinal anesthesia on the gastric emptying rate following preoperative feeding is unknown. The aim of this study was to determine the impact of preoperative feeding with a clear carbohydrate-rich drink on gastric emptying early after orthopedic surgery under spinal anesthesia. METHODS: A total of 110 patients scheduled for semi-elective orthopedic surgery under spinal anesthesia were included in a randomized controlled trial. Patients were randomly assigned to two groups: group 1 (56 patients) received a standardized 200 ml of clear carbohydrate-enriched drink orally 2 hours before surgery; group 2 (54 patients) acted as a control group with no preoperative feeding. Gastric emptying was evaluated with a paracetamol test at five time points: 15 min, 30 min, 60 min, 90 min and 120 min after administration of paracetamol. RESULTS: No significant differences were observed between the two groups in paracetamol plasma concentrations or area under the curve during the early postoperative period. CONCLUSION: In patients undergoing spinal anesthesia, preoperative feeding 2 hours before surgery had no influence on the gastric emptying rate, indicating that preoperative feeding does not increase the risk of gastric-content aspiration and can be given safely.

Elevated second-trimester free beta-hCG as an isolated finding and pregnancy outcomes.

OBJECTIVE: To investigate the relationship between unexplained elevated second-trimester free beta-human chorionic gonadotropin (beta-hCG) levels and pregnancy complications as well as adverse pregnancy outcomes. METHODS: The study cohort comprised 2,110 non-smoking women with chromosomal and structurally normal fetuses at low-risk for both Down's syndrome (risk <1:250) and neural tube defects (maternal serum alpha-fetoprotein <2.0 MoM). A free beta-hCG value of > or =2.0 MoM was used to define the populations with elevated levels of free beta-hCG. Descriptive statistics, chi2 test, Fisher's exact test, and logistic regression analysis were used for statistical analysis, and p < 0.05 was considered statistically significant. RESULTS: The mean maternal age of the study group was significantly lower than in controls (27.9 +/- 4.3 and 30.6 +/- 5.1 years, respectively, p < 0.05), while the proportion of primigravidas was significantly higher compared to that of controls (p < 0.05). After adjustment of the 2 groups according to maternal age and parity, we observed an increased incidence of preeclampsia among women with elevated free beta-hCG levels in relation to controls (p < 0.05). However, a logistic regression analysis demonstrated that the free beta-hCG level was not a predictor of the occurrence of preeclampsia. No significant relationship was found with the incidence of gestational diabetes, oligohydramnios, polyhydramnios, pregnancy-related hypertension, intrauterine growth retardation, preterm delivery, spontaneous abortion and stillbirths (p > 0.05).

The influence of smoking and parity on serum markers for Down's syndrome screening.

OBJECTIVE: To evaluate the impact of smoking and number of previous births on maternal serum levels of alpha-fetoprotein and free beta-subunit of human chorionic gonadotropin (free beta-hCG). METHODS: The study included 3,252 completed unaffected singleton pregnancies that proceeded beyond 37 weeks' gestation and resulted with a birth of healthy child. Smoking status of mothers and data concerning gravidity and parity were collected at the sampling date. Serum markers were measured between 13 and 22 gestational weeks, corrected for maternal weight, and converted to multiples of median (MoM) for unaffected pregnancy of the corresponding gestational age. Median MoM values for both markers were examined in relation to both: smoking habits and number of previous births. RESULTS: Smokers had significantly decreased free beta-hCG MoM values compared to nonsmokers (p < 0.001). The median levels showed a negative relationship with the number of previous births. The significance of a decreasing trend was proved, both in smokers (p < 0.001) and nonsmokers (p < 0.001). The median maternal serum alpha-fetoprotein MoM values did not show any significant dependence, neither with regard to smoking (p = 0.65) nor with regard to parity (p = 0.07). CONCLUSIONS: The recommendable adjustment of serum markers to smoking habits, especially concerning the free beta-hCG levels, would be worthwhile. The evidence of the coexisting influence of parity on serum levels of free beta-hCG, both in smokers and nonsmokers, should perhaps be a stimulus for reconsideration of which corrections the screening performance is dependent on.