Characterizing the Genomic Landscape of the Micropapillary Subtype of Urothelial Carcinoma of the Bladder Harboring Activating Extracellular Mutations of ERBB2.

The micropapillary subtype of urothelial carcinoma (MPUC) of the bladder is a very aggressive histological variant of urothelial bladder cancer (UBC). A high frequency of MPUC contains activating mutations in the extracellular domain (ECD) of ERBB2. We sought to further characterize ERBB2 ECD-mutated MPUC to identify additional genomic alterations that have been associated with tumor progression and therapeutic response. In total, 5,485 cases of archived formalin-fixed, paraffin-embedded UBC underwent comprehensive genomic profiling to identify ERBB2 ECD-mutated MPUC and evaluate the frequencies of genomic co-alterations. We identified 219 cases of UBC with ERBB2 ECD mutations (74% S310F and 26% S310Y), of which 63 (28.8%) were MPUC. Genomic analysis revealed that TERT, TP53, and ARID1A were the most common co-altered genes in ERBB2-mutant MPUC (82.5%, 58.7%, and 39.7%, respectively) and did not differ from ERBB2-mutant non-MPUC (86.5%, 51.9%, and 35.3%). The main differences between ERBB2 ECD-mutated MPUC compared with non-MPUC were KMT2D, RB1, and MTAP alterations. KMT2D and RB1 are tumor-suppressor genes. KMT2D frequency was significantly decreased in ERBB2 ECD-mutated MPUC (6.3%) in contrast to non-MPUC (27.6%; P < .001). RB1 mutations were more frequent in ERBB2 ECD-mutated MPUC (33.3%) than in non-MPUC (17.3%; P = .012). Finally, MTAP loss, an emerging biomarker for new synthetic lethality-based anticancer drugs, was less frequent in ERBB2 ECD-mutated MPUC (11.1%) than in non-MPUC (26.9%; P = .018). Characterizing the genomic landscape of MPUC may not only improve our fundamental knowledge about this aggressive morphological variant of UBC but also has the potential to identify possible prognostic and predictive biomarkers that may drive tumor progression and dictate treatment response to therapeutic approaches.

The influence of different sub-bandage pressure values in the prevention of recurrence of venous ulceration-A ten year follow-up.

OBJECTIVE: The aim of this study was to establish the efficacy of three different strengths of compression systems in the prevention of venous leg ulcer (VLU) recurrences during a 10-year follow up period. METHODS: An open, prospective, randomized, single-center study included 477 patients (240 men, 237 women; mean age 59 years). Patients were randomized into three groups: Group A) 149 patients (allocated to wear elastic stocking 18-25 mmHg). Group B) 167 patients (wearing compression device exerting 25-35 mmHg), and Group C) 161 patients (treated with multilayer compression system exerting 35-50 mmHg). RESULTS: Overall, 65% (234/360) of patients had recurrent VLU within 10 years. Recurrence occurred in 120 (96%) of 125 in group A, in 89 (66.9%) of 133 patients in group B and in 25 (24.5%) of 102 patients in group C (p < 0.05). CONCLUSION: Compression systems with the higher compression class provide lower recurrence rate.

Clinical features of patients with MTAP-deleted bladder cancer.

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. FGFR2 and FGFR3 mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes. We describe herein the clinical and pathologic features of patients with an emerging subtype of bladder cancer characterized by deletion of the gene MTAP encoding the enzyme S-Methyl-5'-thioadenosine phosphatase, a potential biomarker of response to pemetrexed. We performed a retrospective analysis of 61 patients with advanced urothelial carcinoma for whom demographics, pathologic specimens, next generation sequencing, and clinical outcomes were available. We compared the frequency of histology variants, upper tract location, pathogenic gene variants, tumor response, progression free survival (PFS) and overall survival (OS) between patients with tumors harboring MTAP deletion (MTAP-del) and wild type tumors (MTAP-WT). A propensity score matching of 5 covariates (age, gender, presence of variant histology, prior surgery, and prior non-muscle invasive bladder cancer) was calculated to compensate for disparity when comparing survival in these subgroups. Non-supervised clustering analysis of differentially expressed genes between MTAP-del and MTAP-WT urothelial carcinomas was performed. MTAP-del occurred in 19 patients (31%). Tumors with MTAP-del were characterized by higher prevalence of squamous differentiation (47.4 vs 11.9%), bone metastases (52.6 vs 23.5%) and lower frequency of upper urinary tract location (5.2% vs 26.1%). Pathway gene set enrichment analysis showed that among the genes upregulated in the MTAP-del cohort, at least 5 were linked to keratinization (FOXN1, KRT33A/B, KRT84, RPTN) possibly contributing to the higher prevalence of squamous differentiation. Alterations in the PIK3 and MAPK pathways were more frequent when MTAP was deleted. There was a trend to inferior response to chemotherapy among MTAP-del tumors, but no difference in the response to immune checkpoint inhibitors or enfortumab. Median progression free survival after first line therapy (PFS1) was 5.5 months for patients with MTAP-WT and 4.5 months for patients with MTAP-del (HR = 1.30; 95% CI, 0.64-2.63; P = 0.471). There was no difference in the time from metastatic diagnosis to death (P = 0.6346). Median OS from diagnosis of localized or de novo metastatic disease was 16 months (range 1.5-60, IQR 8-26) for patients with MTAP-del and 24.5 months (range 3-156, IQR 16-48) for patients with MTAP-WT (P = 0.0218), suggesting that time to progression to metastatic disease is shorter in MTAP-del patients. Covariates did not impact significantly overall survival on propensity score matching. In conclusion, MTAP -del occurs in approximately 30% of patients with advanced urothelial carcinoma and defines a subgroup of patients with aggressive features, such as squamous differentiation, frequent bone metastases, poor response to chemotherapy, and shorter time to progression to metastatic disease.

Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery.

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.

p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma.

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT. Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan-Meier method. Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14-0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18-0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22-0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1-4.2, p = 0.03). Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.

In silico development of potential therapeutic for the pain treatment by inhibiting voltage-gated sodium channel 1.7.

The voltage-gated sodium channel Nav1.7 can be considered as a promising target for the treatment of pain. This research presents conformational-independent and 3D field-based QSAR modeling for a series of aryl sulfonamide acting as Nav1.7 inhibitors. As descriptors used for building conformation-independent QSAR models, SMILES notation and local invariants of the molecular graph were used with the Monte Carlo optimization method as a model developer. Different statistical methods, including the index of ideality of correlation, were used to test the quality of the developed models, robustness and predictability and obtained results were good. Obtained results indicate that there is a very good correlation between 3D QSAR and conformation-independent models. Molecular fragments that account for the increase/decrease of a studied activity were defined and used for the computer-aided design of new compounds as potential analgesics. The final evaluation of the developed QSAR models and designed inhibitors were carried out using molecular docking studies, bringing to light an excellent correlation with the QSAR modeling results.

A Risk Stratification Model for Cardiovascular Complications during the 3-Month Period after Major Elective Vascular Surgery.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). PURPOSE: The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). MATERIALS AND METHODS: We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. RESULTS: During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). CONCLUSION: We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.

A randomized trial of class 2 and class 3 elastic compression in the prevention of recurrence of venous ulceration.

BACKGROUND: Venous leg ulcers (VLUs) are a major health problem because of their high prevalence and associated high cost of care. Despite the widespread use of compression, treatment recurrence rates remain high. Numerous studies have suggested that regular use of compression stockings reduces VLU recurrences. However, there are limited data concerning how long compression hosiery should be worn after ulcer healing and which class of compression hosiery achieves better results in the prevention of VLU recurrences. METHODS: An open, prospective, randomized, single-center study with a 5-year follow-up was performed to establish the efficacy of two different strengths of knee-high compression hosiery (class 2 and class 3) in the prevention of VLU recurrences. The study included patients with recently healed venous ulcers and no significant arterial disease, rheumatoid disease, diabetes mellitus, and restriction in range of ankle movement. Overall, 361 patients were randomized, and 308 patients (170 men, 138 women; mean age, 59 years) completed the study. Patients were randomized into two groups: group A, 186 patients who wore a heel-less open-toed elastic class 3 compression device knitted in tubular form (Tubulcus; Laboratoires Innothera, Arcueil, France); and group B, 175 patients who wore a class 2 elastic stocking (Rudo, Nis, Serbia). All patients were instructed to wear compression stockings continuously for the first 2 years of follow-up (both during the day and at night). In the third, fourth, and fifth years of follow-up, patients were instructed to wear elastic stockings during the day only. The main outcome measures were recurrence of leg ulceration and compliance with the treatment. RESULTS: Rates of ulcer recurrence after the 5 years of follow-up were 28.98% for the compression class 3 group and 60% for the compression class 2 group (P < .001, log-rank test). Patients in the compression class 3 group experienced significantly longer absolute (46 vs 40 months; P < .001, Mann-Whitney U test) and proportional (77% vs 67%; P < .001, Mann-Whitney U test) ulcer-free time after 5 years than those in the compression class 2 group. Rates of noncompliance after 5 years were 10.23% for the compression class 3 group and 6.25% for the compression class 2 group (P = .188, χ2 test). CONCLUSIONS: The results obtained in this study suggest that class 3 compression stockings provide a statistically significant lower recurrence rate compared with the class 2 compression stockings.

The anesthetic action of some polyhalogenated ethers-Monte Carlo method based QSAR study.

Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of action is unknown, QSAR modelling is essential in drug development. To investigate the aspects of their anesthetic, QSAR models based on the Monte Carlo method were developed for a set of polyhalogenated ethers. Until now, their anesthetic action has not been completely defined, although some hypotheses have been suggested. Therefore, a QSAR model should be developed on molecular fragments that contribute to anesthetic action. QSAR models were built on the basis of optimal molecular descriptors based on the SMILES notation and local graph invariants, whereas the Monte Carlo optimization method with three random splits into the training and test set was applied for model development. Different methods, including novel Index of ideality correlation, were applied for the determination of the robustness of the model and its predictive potential. The Monte Carlo optimization process was capable of being an efficient in silico tool for building up a robust model of good statistical quality. Molecular fragments which have both positive and negative influence on anesthetic action were determined. The presented study can be useful in the search for novel anesthetics.

Effectiveness and safety of computed tomography-guided radiofrequency ablation of renal cancer: a 14-year single institution experience in 203 patients.

OBJECTIVES: To define effectiveness and safety of CT-guided radiofrequency ablation (RFA) of renal tumours and prognostic indicators for treatment success. METHODS: Patients with a single treatment of a solitary, biopsy-proven renal tumour with intent to cure over a 14-year period were included (n = 203). Probability of residual disease over time, complication rates and all-cause mortality were assessed in relation to multiple variables. RESULTS: Mean tumour size was 2.5 cm (range 1.0-6.0). Mean follow-up was 34.1 months (range 1-131). There was an increase in likelihood of residual disease for tumours ≥3.5 cm (P < 0.05), clear cell subtype of renal cell carcinoma (P ≤ 0.005) and maximum treatment temperature ≤70 °C (P < 0.05). There was a decrease in likelihood of residual disease for exophytic tumours (P = 0.01) and no difference based on age, gender, tumour location or type of radio freqency (RF) electrode used. Major complications occurred in 3.9 %. Median post-treatment survival was 7 years for patients with tumours <4 cm, and 5-year overall survival was 80 %. Probability of minor complication increased with tumour size (P = 0.03), as did all-cause mortality (P = 0.005). CONCLUSIONS: CT-guided RFA is safe and effective for early-stage renal cancer, particularly for exophytic tumours measuring <3.5 cm. Overall 5-year survival with tumours <4 cm is comparable to partial nephrectomy. KEY POINTS: • Prognostic indicators for success of CT-guided RFA of renal tumours are reported. • Tumour size ≥3.5 cm confers an increased risk for residual tumour. • Clear cell renal cell carcinoma subtype confers increased risk for residual tumour. • Tmax <70 °C within the ablation zone confers increased risk for residual tumour. • Exophytic tumours have a lower probability of residual disease.

Analysis of a large single-center experience with robot-assisted pyeloplasty.

OBJECTIVES: To report a single-center experience with robot-assisted pyeloplasty. METHODS: Medical records of 100 consecutive robot-assisted pyeloplasty cases carried out between May 2004 and August 2010 were retrospectively reviewed, and major perioperative parameters were recorded. Patients underwent functional (renal scan) and/or anatomical (ultrasound or computerized tomoghraphy) imaging at 6 months. RESULTS: The mean patient age was 39.8 years. A total of 12 patients underwent prior attempts at repair. Ureteral stents were placed in all patients except one, and closed-suction drains were placed in 59 patients. There were two intraoperative complications and two postoperative complications requiring surgical intervention. One patient with a complex prior surgical history developed a urine leak that was managed with prolonged drainage. A total of 42 patients were discharged on postoperative day 1, and 44 were discharged on postoperative day 2. Mean length of follow up was 22.8 months. The operative success rate was 96%. CONCLUSIONS: The majority of patients undergoing robot-assisted pyeloplasty can expect a short hospitalization with minimal morbidity. The operative success rate is high, even in patients with prior attempts at repair. Complication rates including urine leaks are quite low, and routine placement of a closed-suction drain is likely to be unnecessary.

Factors influencing the choice of antidepressants: a study of antidepressant prescribing practice at University Psychiatric Clinic in Belgrade.

BACKGROUND/AIM: Antidepressants are a widely used class of drugs. The aim of this study was to investigate different aspects of antidepressant prescribing practice at University Psychiatric Clinic in Belgrade. METHODS: This cross-sectional study was carried out by retrospective analysis of the patient's medical charts. The study included all patients with antidepressant prescribed at discharge during 2009 (n = 296). The evaluation was focused on patient-related factors (socio-demographic and illness related), psychiatrist-related factors (sex and duration of working experience) and drug related factors (type of antidepressant, dose, polypharmacy and reimbursement by national health insurance). RESULTS: Antidepressants were prescribed for unipolar depression (F32-34, ICD X) either without comorbidity (46.2%) or with comorbidity (24.7%), mostly as a monotherapy (91% had one antidepressant), to the patients who were 65% female, aged 50.1 +/- 8.9, most of them with 12 years of education (52.6%), married (69.3%) and employed (55.9%). The majority of patients had a history of two hospitalizations (Med 2; 25th-75th perc. 1-4) during nine years (Med 9; 25th-75th perc. 2-15) after the first episode of depression. Among them, 19% were found to be suicidal in a lifetime. The single most prescribed antidepressant was sertraline (20.4%), followed by fluoxetine (13.3%) and maprotiline (11.7%). Utilization of antidepressants was positively correlated with the rate of reimbursement (p < 0.01). The most prescribed antidepressant group was selective serotonin reuptake inhibitors (SSRI) (47.8%), followed by tricyclic antidepresants (TCA) (25.3%) and new antidepressants - venlafaxine, tianeptine, mirtazapine, bupropion, trazodone (15.1%). Most of the drugs were prescribed in doses which are at the lower end of the recommended dose-range. Regarding severity of the actual depressive episode, TCA were prescribed for severe depression with psychotic features, while SSRI were choice for episodes with moderate symptom severity (p = 0.01). Psychiatrists with longer working age (20-30 years) hesitated to prescribe new antidepressants in comparison to younger colleagues (p = 0.01). CONCLUSION: Economic issues in Serbia as developing country influence the choice of antidepressants, as well as a psychiatrist's working age and severity of depression. However, SSRI are the drugs of the first choice, as it was shown in most of the developed countries nowadays.

Robot-assisted partial nephrectomy: analysis of the first 100 cases from a single institution.

Robot-assisted partial nephrectomy (RAPN) is an alternative to open and laparoscopic partial nephrectomy for small renal tumors. Our objectives were to report our experience and short-term outcomes from the first 100 cases of robot-assisted partial nephrectomy (RAPN) performed at a single institution, as well as to evaluate the effect of the learning curve and identify any factors associated with adverse perioperative outcomes. Patient records of the first 100 RAPN cases performed by three surgeons between October 2007 and March 2010 were retrospectively reviewed. The cases were divided into two groups to analyze a possible learning curve effect. Group 1 consisted of the first half (chronologically) of the cases performed by each surgeon, and Group 2 consisted of the second half. For the entire series, the median warm ischemia time was 24 min (range 11-49), mean length of follow-up was 13.4 months, and the median postoperative change in glomerular filtration rate (GFR) was -6.6 mL/min/1.73 m(2). Three patients had microscopically positive margins on final pathology, three intraoperative complications occurred, and 13 postoperative complications were recorded (10 Clavien grade IIIa or less). Median operative time was significantly longer in Group 1 (193 min) than in Group 2 (165 min, P = 0.003). Multivariate analysis identified male gender and cases done in Group 1 to be associated with increased operative time, while male gender and higher nephrometry scores were associated with increased blood loss. Tumor characteristics associated with greater reductions in GFR included higher nephrometry scores, endophytic tumors, and hilar tumors. In conclusion, RAPN appears to be safe and the major effect of the learning curve appears to be on operative time. Warm ischemia times are sufficiently low to prevent significant renal impairment, while male gender and higher nephrometry scores may be predictors of longer operative times and more intraoperative blood loss. Overall operative time decreased with increasing case volume, although this was not uniform among the three surgeons in the study. Further longitudinal study is necessary to establish oncologic outcomes.

Risk factors associated with carotid artery puncture following landmark-guided internal jugular vein cannulation attempts.

OBJECTIVE: The relationship between certain risk factors and carotid artery puncture (CAP) as an early mechanical complication following internal jugular vein cannulation attempts (IJVCAs) was evaluated. METHODS: In a retrospective 1-year observational single-center study, 86 IJVCAs conducted in the operating room by 4 competent anesthesiologists were evaluated. Age, gender, puncture side, number of cannulation attempts, circumstances of the procedure and incidence of CAP were obtained from medical records. RESULTS: Of the 86 IJVCAs performed in patients aged 18-75 years, CAP occurred in 8 (9.3%): 5 (5.8%) in patients >65 years and 3 (3.5%) in patients <65 years of age. CAP was not associated with patient's age (p = 0.11) and gender (p = 0.76). Multiple cannulation attempts (OR = 26.25; 95% CI = 4.52-152.51; p < 0.001) and placement of CVC under emergency conditions (OR = 14.84; 95% CI = 1.73-127.22; p = 0.014) increased the risk for CAP significantly. Also, the risk for CAP was higher when IJVCAs were performed before induction of general anesthesia (OR = 15.75; 95% CI = 1.83-135.1; p = 0.019). CAP was more likely to happen during left-sided than right-sided IJVCA (OR = 5.98; 95% CI = 1.29-27.59; p = 0.022). In addition, left-sided attempts considerably increased the risk for multiple cannulation attempts (OR = 2.782; 95% CI = 1.342-3.965; p < 0.01). Also, manifold cannulation attempts were more frequent if the IJVCA was performed before induction of anesthesia (OR = 4.219; CI = 1.579-11.271; p = 0.004). CONCLUSIONS: Our results strongly suggest that left-sided, multiple IJVCAs, performed under emergency conditions in conscious patients in the operating room, represent considerable risks for possible CAP.

The influence of different sub-bandage pressure values on venous leg ulcers healing when treated with compression therapy.

BACKGROUND: Venous leg ulcers (VLU) have a huge social and economic impact. An estimated 1.5% of European adults will suffer a venous ulcer at some point in their lives. Despite the widespread use of bandaging with high pressure in the treatment of this condition, recurrence rates range between 25% to 70%. Numerous studies have suggested that the compression system should provide sub-bandage pressure values in the range from 35 mm Hg to 45 mm Hg in order to achieve the best possible healing results. METHODS: An open, randomized, prospective, single-center study was performed in order to determine the healing rates of VLU when treated with different compression systems and different sub-bandage pressure values. One hundred thirty-one patients (72 women, 59 men; mean age, 59-years-old) with VLU (ulcer surface >3 cm(2); duration >3 months) were randomized into three groups: group A - 42 patients who were treated using an open-toed, elastic, class III compression device knitted in tubular form (Tubulcus, Laboratoires Innothera, Arcueil, France); group B - 46 patients treated with the multi-component bandaging system comprised of Tubulcus and one elastic bandage (15 cm wide and 5 cm long with 200% stretch, Niva, Novi Sad, Serbia); and group C - forty-three patients treated with the multi-component bandaging system comprised of Tubulcus and two elastic bandages. Pressure measurements were taken with the Kikuhime device (TT MediTrade, Soro, Denmark) at the B1 measuring point in the supine, sitting, and standing positions under the three different compression systems. RESULTS: The median resting values in the supine and standing positions in examined study groups were as follows: group A - 36.2 mm Hg and 43.9 mm Hg; group B - 53.9 mm Hg and 68.2 mm Hg; group C - 74.0 mm Hg and 87.4 mm Hg. The healing rate during the 26-week treatment period was 25% (13/42) in group A, 67.4% (31/46) in group B, and 74.4% (32/43) in group C. The success of compression treatment in group A was strongly associated with the small ulcer surface (<5 cm(2)) and smaller calf circumference (CC; <38 cm). On the other hand, compliance in group A was good. In groups B and C, compliance was poor in patients with small CC, but the healing rate was high, especially in patients with large ulcers and a large CC (>43 cm). CONCLUSION: The results obtained in this study indicate that better healing results are achieved with two or multi-component compression systems than with single-component compression systems and that a compression system should be individually determined for each patient according to individual characteristics of the leg and CC. Target sub-bandage pressure value (B1 measuring point in the sitting position) of the compression system needed for the ulcer healing could be determined according to a simple formula, CC + CC/2.

[Stigmatization of a person visiting psychiatrist depends on observer's gender].

INTRODUCTION: The two types of stigmatization are social stigma, which includes discrimination, underestimation and distance in various social circumstances and personal stigma, which includes private relation i.e. a contact in person with stigmatized subject. Majority of recent publications has shown gender asymmetry in stigmatization (mostly indicating male predominance in stigmatizing processes), whereas the opposite data can be also found in some publications. The present study was aimed at exploring the relation of students' gender with their tendency to stigmatize subjects visiting a psychiatrist and at analyzing whether the gender influences the process of stigmatization. MATERIAL AND METHODS: The survey included 523 students (227 on the second and 296 on the sixth year of School of Medicine, University of Belgrade). The instrument consisted of a vignette with questionnaire (14 items). Four versions of vignette were distributed: with/without "label" and male/female subject in the vignette. RESULTS: A more personal stigmatization was evident in the female students (p < 0.05). while no gender-differences existed in social stigmatization (p > 0.05). The stigmatization positively correlated with the intimacy of student's relation with the subject going to a psychiatrist. A higher rate of stigmatization was evident if the vignette was showing a person of the opposite gender. DISCUSSION AND CONCLUSION: This is a unique study which analyzes separately the gender of a stigmatizing subject versus the subject being stigmatized and types of stigmatization. The data obtained should contribute to recognizing, understanding and controlling the widespread problem of stigma.

Prenatal stress during the 1999 bombing associated with lower birth weight-a study of 3,815 births from Belgrade.

During the 3-month bombing of Serbia (March 24-June 9, 1999), the entire population, including pregnant females as an especially vulnerable group, was exposed to a high degree of stress. This is the first study to explore the effects of prenatal stress during the 1999 bombing of Belgrade on the main obstetric characteristics of newborns. The design of the study was retrospective cross-sectional. The total number of birth records in the sample was 3,815, namely, 1,198 from the group exposed to prenatal stress and 1,251 and 1,366 from the respective control periods, years 1996 and 2003, when no stressful events affected the city. We found that exposed mothers gave birth to infants with statistically significantly lower birth weight (BW; mean difference = 86 g, 95% confidence interval = 67 to 104; F ((1, 3,349)) = 80.8, p < 0.001, eta (p) (2) = 0.024), when controlling for confounding effects of body length and head circumference. There was no specific relation between the trimester of stress exposure and BW in infants born in 1999. Neither increased frequency of preterm deliveries nor more complications of pregnancy and delivery were found in the given sample. Possible consequences of lower BW on psychosocial and somatic functioning should be evaluated through the lifetime.

How medical students in their pre-clinical year perceive psychiatry as a career: the study from Belgrade.

BACKGROUND: Taking the Initiative to evaluate students' affinity toward psychiatry seems to be a global issue and is an essential part of programs to improve the status of the profession. The aim of this study is to explore medical students' attitudes toward psychiatry in comparison to other residencies (internal medicine, surgery, pediatrics, gynecology and general medicine) in the pre-clinical year and to observe which factors influence the creation of these attitudes. SUBJECTS AND METHODS: The survey included 114 students of the second year, School of Medicine in Belgrade (academic year 2007/08). The data was collected trough a 23-item questionnaire. RESULTS: Fifteen percent of students stated that psychiatry was their career of choice, while 25% expressed a strong aversion. Psychiatry was ranked less attractive than internal medicine, surgery and pediatrics, but more attractive than general medicine or gynecology. Those who like psychiatry attributed more importance to an interesting and challenging job than to prestige and financial reward. Also, they found this field to be intellectually challenging and to rapidly expand the frontier of medicine. Students with negative attitude were convinced that psychiatry was lacking in scientific foundation and was clinically inefficient, they disliked intensive emotional involvement, exposure to stress and frequent unpleasant situations and had prejudices toward the patients or simply a lack of the interest. CONCLUSION: The present study is the first of its kind in Serbia which used a precise and internationally comparable methodological instrument and It shows that pre-clinical medical students at the University of Belgrade, have a stronger affinity towards psychiatry when compared to their peers from most countries worldwide. Also, the study points out the fact that prejudices toward patients with mental dysfunctions and lack of confidence in the efficacy of psychiatric treatment should be specially targeted by the curriculum in the later part of undergraduate education. How this will affect the attitude of clinical students and graduates is to be examined.

Risk factors related to the failure of venous leg ulcers to heal with compression treatment.

BACKGROUND: Compression therapy is the most widely used treatment for venous leg ulcers and it was used in different forms for more than 400 years. Published healing rates of venous ulcers obtained with compression therapy vary widely from 40-95%. According to numerous studies, it has been suggested that the application of external pressure to the calf muscle raises the interstitial pressure resulting in improved venous return and reduction in the venous hypertension. Several risk factors have been identified to be correlated with the failure of venous leg ulcers to heal with compression therapy (longer ulcer duration; large surface area; fibrinous deposition present on >50% of the wound surface and an Ankle Brachial Pressure Index (ABPI) of <0.85. METHODS: An open prospective single-center study was performed in order to determine possible risk factors associated with the failure of venous ulcers to heal when treated with multi-layer high compression bandaging system for 52 weeks. In the study, 189 patients (101 women, 88 men; mean age 61 years) with venous leg ulcers (ulcer surface >5 cm(2); duration >3 months) were included. The study excluded patients with arterial disease (ABPI <0.8), heart insufficiency with ejection fraction (EF) <35, pregnancy, cancer disease, rheumatoid arthritis, and diabetes. Based on clinical opinion and available literature, the following were considered as potential risk factors: sex, age, ulceration surface, time since ulcer onset, previous operations, history of deep vein thrombosis, body mass index (BMI), reduction in calf circumference >3 cm during the first 50 days of treatment, walking distance during the day <200 meters, calf:ankle circumference ratio <1.3, fixed ankle joint, history of surgical wound debridement, >50% of wound covered with fibrin, depth of the wound >2 cm. RESULTS: Within 52 weeks of limb-compression therapy, 24 (12.7%) venous ulcers had failed to heal. A small ulceration surface (<20 cm(2)), the duration of the venous ulcer <12 months, a decrease in calf circumference of more than 3 cm, and emergence of new skin islets on >10% of wound surface during the first 50 days of treatment were favorable prognostic factors for ulcer healing. A large BMI (>33 kg/m(2)), short walking distance during the day (<200 m), a history of wound debridement, and ulcers with deepest presentation (>2 cm) were indicators of slow healing. Calf:ankle circumference ratio <1.3, fixed ankle joint, and reduced ankle range of motion were the only independent parameters associated with non-healing (P < .001). CONCLUSION: The results obtained in this study suggest that non-healing venous ulcers are related to the impairment of the calf muscle pump.