Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma.

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Transcultural adaptation and validation of the Serbian version of Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-Patient Satisfaction (FACIT-TS-PS) questionnaire.

OBJECTIVE: Transcultural adaptation and validation of FACIT-TS-PS questionnaire to Serbian language. METHODS: Standard forward and backward translation from English to Serbian language was performed. Pilot testing of FACIT-TS-PS was conducted on 12 patients with a confirmed diagnosis of malignant tumor. The study included 154 patients with malignant disease. The Questionnaire of Patient Satisfaction was used as a validated tool to evaluate concurrent validity of FACIT-TS-PS questionnaire. Reproducibility was tested on 30 subjects who answered the questionnaire for the second time two weeks later. RESULTS: Three FACIT-TS-PS subscales (Physician Communication, Treatment Staff Communication and Nurse Communication) demonstrated satisfactory construct validity using Cronbach's alpha, the remaining two subscales (Technical Competence and Confidence & Trust) showed high ceiling effect. Treatment Staff Communication subscale showed large floor effect. Concurrent validity was demonstrated by correlation with the two dimensions of the Questionnaire of Patient Satisfaction. Satisfactory reproducibility was demonstrated on 30 patients who filled the questionnaire for the second time two weeks after initial interview. CONCLUSION: The Serbian version of FACIT-TS-PS with the omission of Treatment Staff Communication subscale could be used as a valid instrument to assess patient and treatment satisfaction in chronically ill patients in the Serbian population. Omission of Treatment Staff Communication subscale is necessary because it contains questions not relevant for patients in Serbian healthcare system.

Cost-effectiveness of the Perioperative Pain Management Bundle a registry-based study.

Introduction: The Perioperative Pain Management Bundle was introduced in 10 Serbian PAIN OUT network hospitals to improve the quality of postoperative pain management. The Bundle consists of 4 elements: informing patients about postoperative pain treatment options; administering a full daily dose of 1-2 non-opioid analgesics; administering regional blocks and/or surgical wound infiltration; and assessing pain after surgery. In this study, we aimed to assess the cost-effectiveness of the Bundle during the initial 24 h after surgery. Materials and methods: The assessment of cost-effectiveness was carried out by comparing patients before and after Bundle implementation and by comparing patients who received all Bundle elements to those with no Bundle element. Costs of postoperative pain management included costs of the analgesic medications, costs of labor for administering these medications, and related disposable materials. A multidimensional Pain Composite Score (PCS), the effectiveness measurement, was obtained by averaging variables from the International Pain Outcomes questionnaire evaluating pain intensity, interference of pain with activities and emotions, and side effects of analgesic medications. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental change in costs divided by the incremental change in PCS and plotted on the cost-effectiveness plane along with the economic preference analysis. Results: The ICER value calculated when comparing patients before and after Bundle implementation was 181.89 RSD (1.55 EUR) with plotted ICERs located in the northeast and southeast quadrants of the cost-effectiveness plane. However, when comparing patients with no Bundle elements and those with all four Bundle elements, the calculated ICER was -800.63 RSD (-6.82 EUR) with plotted ICERs located in the southeast quadrant of the cost-effectiveness plane. ICER values differ across surgical disciplines. Conclusion: The proposed perioperative pain management Bundle is cost-effective. The cost-effectiveness varies depending on the number of implemented Bundle elements and fluctuates across surgical disciplines.

Economic Justification Analysis of Minimally Invasive versus Conventional Aortic Valve Replacement.

There is no definitive consensus about the cost-effectiveness of minimally invasive aortic valve replacement (AVR) (MI-AVR) compared to conventional AVR (C-AVR). The aim of this study was to compare the rate of postoperative complications and total hospital costs of MI-AVR versus C-AVR overall and by the type of aortic prosthesis (biological or mechanical). Our single-center retrospective study included 324 patients over 18 years old who underwent elective isolated primary AVR with standard stented AV prosthesis at the Institute for Cardiovascular Diseases "Dedinje" between January 2019 and December 2019. Reintervention, emergencies, combined surgical interventions, and patients with sutureless valves were excluded. In both MI-AVR and C-AVR, mechanical valve implantation contributed to overall reduction of hospital costs with equal efficacy. The cost-effectiveness ratio indicated that C-AVR is cheaper and yielded a better clinical outcome with mechanical valve implantation (67.17 vs. 69.5). In biological valve implantation, MI-AVR was superior. MI-AVR patients had statistically significantly higher LVEF and a lower Euro SCORE than C-AVR patients (Mann-Whitney U-test, p = 0.002 and p = 0.002, respectively). There is a slight advantage to MI-AVR vs. C-AVR, since it costs EUR 9.44 more to address complications that may arise. Complications (mortality, early reoperation, cerebrovascular insult, pacemaker implantation, atrial fibrillation, AV block, systemic inflammatory response syndrome, wound infection) were less frequent in the MI-AVR, making MI-AVR more economically justified than C-AVR (18% vs. 22.1%).

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19. Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity. Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135). Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis-A Pilot Study.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

BACKGROUND: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. PURPOSE: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. METHODS: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27-74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10-40 µg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. RESULTS: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967-1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001-0.534; p = 0.019; OR: 1.147; 95% CI: 1.042-1.263; p = 0.005; respectively). CONCLUSIONS: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

How Much Country Economy Influences ECC Profile in Serbian Children-A Macro-Level Factor Analysis.

Introduction: Serbia has universal health coverage (UHC) for pediatric dental care and similar country distribution for dentists and physicians per 1,000 inhabitants. However, a high prevalence of early childhood caries (ECC) with wide variation across the country was observed in previous studies. This paper aimed to analyze the association between economic and healthcare country macro-level factors with ECC prevalence and treatment. Method: The outcome variables were ECC prevalence and frequency of untreated ECC in 36- to 71-month-olds. Cross-sectional pathfinder survey on a nationally representative sample of children was conducted in order to obtain data. Independent variables included the following: gross domestic product (GDP), social and health care budget beneficiaries' expenditures, local self-government budget, unemployment rate, population density and density of physicians and dentists. Guided by the WHO's Basic Methods for Oral Health Surveys stratified cluster sample, 17 sites were randomly chosen to obtain adequate distribution of data regarding urban, peri-urban and rural areas in each analyzed statistical territorial unit. The variables were analyzed using the independent t-test or Mann-Whitney U test. A probability value of <0.05 was considered significant. Results: The final sample included 864 children aged 36 to 71 months. Observed prevalence of ECC was 41.1%. Although no statistically significant difference was found, children with ECC compared to healthy children were living in parts of the country with averages of ≈122€ lower GDP per capita, ≈4€ lower social and health care expenditures per capita, 9 inhabitants per km2 lower population density, almost 7€ per capita lower local self-government budget and a 0.6% higher unemployment rate. Furthermore, although without a statistically significant difference, untreated ECC was associated with ≈302€ lower GDP per capita, ≈12€ lower social and health care expenditures per capita, 34 inhabitants per km2 lower population density, almost 20€ per capita lower local self-government budget and a 1.7% higher unemployment rate. Conclusions: This study, performed in a nationally representative sample of preschool children, revealed the association of economic macro-level factors with ECC prevalence and its (non-) treatment. Further research on a larger sample is necessary to confirm the results. These findings suggest that most of the public-health efforts regarding prevention and early treatment of ECC should be directed at regions with lower economic performance.

Prognostic value of health-related quality of life in elderly patients hospitalized with heart failure.

Purpose: Previous research has shown that poor health-related quality of life (HRQOL) is associated with adverse long-term prognosis in patients with heart failure (HF); however, there have been inconsistencies among studies and not all of them confirmed the prognostic value of HRQOL. In addition, few studies involved elderly patients and most focused on all-cause mortality and HF-related hospitalization as outcomes. The aim of our study was to determine whether HRQOL is a predictor and an independent predictor of long-term cardiac mortality, all-cause mortality, and HF-related rehospitalization in elderly patients hospitalized with HF. Patients and methods: This prospective observational study included 200 elderly patients hospitalized with HF in Serbia. HRQOL was measured using the Minnesota Living with Heart Failure questionnaire (MLHFQ). The median follow-up period was 28 months. The primary outcome was cardiac mortality, and all-cause mortality and HF-related rehospitalization were secondary outcomes. Survival analysis was conducted using the Kaplan-Meier method and Cox-proportional hazards regression. Results: Subjects with poor HRQOL (higher than the median MLHFQ score) had a higher probability of cardiac mortality (P=0.029) and HF-related rehospitalization (P=0.001) during long-term follow-up. Poor HRQOL was an independent predictor of cardiac mortality (HR: 2.051, 95% CI: 1.260-3.339, P=0.004), all-cause mortality (HR: 1.620, 95% CI: 1.076-2.438, P=0.021), and HF-related rehospitalization (HR: 2.040, 95% CI: 1.290-3.227, P=0.002). Conclusion: HRQOL is an independent predictor of long-term cardiac mortality in elderly patients hospitalized with HF. It also independently predicts all-cause mortality and HF-related rehospitalization. HRQOL could be used as a complementary clinical predictive tool in this patient population.

Comparative analysis of the current payment system for hospital services in Serbia and projected payments under diagnostic related groups system in urology.

BACKGROUND/AIM: Global budget per calendar year is a traditional method of funding hospitals in Serbia. Diagnose related groups (DGR) is a method of hospital payment based on classification of patients into groups with clinically similar problems and similar utilization of hospital resources. The aim of this study was to compare current methods of hospital services payment with the projected costs by DRG payment method in urology. METHODS: The data were obtained from the information system used in the Clinical Hospital Center "Dr. Dragisa Misovic"--Dedinje in Belgrade, Serbia. The implemented hospital information system was the main criterion for selection of healthcare institutions. The study included 994 randomly selected patients treated surgically and conservatively in 2012. RESULTS: Average costs under the current payment method were slightly higher than those projected by DRG, however, the variability was twice as high (54,111 ± 69,789 compared to 53,434 ± 32,509, p < 0.001) respectively. The univariate analysis showed that the highest correlation with the current payment method as well as with the projected one by DRG was observed in relation to the number of days of hospitalization (ρ = 0.842, p < 0.001, and ρ = 0.637, p < 0.001, respectively). Multivariate regression models confirmed the influence of the number of hospitalization days to costs under the current payment system (ß = 0.843, p < 0.001) as well as under the projected DRG payment system (ß = 0.737, p < 0.001). The same predictor was crucial for the difference in the current payment method and the pro- jected DRG payment methods (ß = 0.501, p < 0.001). CONCLUSION: Payment under the DRG system is administratively more complex because it requires detailed and standardized coding of diagnoses and procedures, as well as the information on the average consumption of resources (costs) per DRG. Given that aggregate costs of treatment under two hospital payment methods compared in the study are not significantly different, the focus on minor surgeries both under the current hospital payment method and under the introduced DRG system would be far more cost-effective for a hospital as great variations in treatment performance (reductions of days of hospitalization and complications), and consequently invoiced amounts would be reduced.

Radiographic assessment of lower third molar eruption in different anteroposterior skeletal patterns and age-related groups.

OBJECTIVE: To analyze radiographic predictors for lower third molar eruption among subjects with different anteroposterior skeletal relations and of different age groups. MATERIALS AND METHODS: In total, 300 lower third molars were recorded on diagnostic digital orthopantomograms (DPTs) and lateral cephalograms (LCs). The radiographs were grouped according to sagittal intermaxillary angle (ANB), subject age, and level of lower third molar eruption. The DPT was used to analyze retromolar space, mesiodistal crown width, space/width ratio, third and second molar angulation (α, γ), third molar inclination (ß), and gonion angle. The LC was used to determine ANB, angles of maxillar and mandibular prognathism (SNA, SNB), mandibular plane angle (SN/MP), and mandibular lengths. A logistic regression model was created using the statistically significant predictors. RESULTS: The logistic regression analysis revealed a statistically significant impact of ß angle and distance between gonion and gnathion (Go-Gn) on the level of lower third molar eruption (P < .001 and P < .015, respectively). The retromolar space was significantly increased in the adult subgroup for all skeletal classes. The lower third molar impaction rate was significantly higher in the adult subgroup with the Class II (62.3%) compared with Class III subjects (31.7%; P < .013). CONCLUSION: The most favorable values of linear and angular predictors of mandibular third molar eruption were measured in Class III subjects. For valid estimation of mandibular third molar eruption, certain linear and angular measures (ß angle, Go-Gn), as well as the size of the retromolar space, need to be considered.

Procalcitonin and BISAP score versus C-reactive protein and APACHE II score in early assessment of severity and outcome of acute pancreatitis.

BACKGROUND/AIM: Early assessment of severity and continuous monitoring of patients are the key factors for adequate treatment of acute pancreatitis (AP). The aim of this study was to determine the value of procalcitonin (PCT) and Bedside Index for Severity in Acute Pancreatitis (BISAP) scoring system as prognostic markers in early stages of AP with comparison to other established indicators such as C-reactive protein (CRP) and Acute Physiology and Chronic Health Evaluation (APACHE) II score. METHODS: This prospective study included 51 patients (29 with severe AP). In the first 24 h of admission in all patients the APACHE II score and BISAP score, CRP and PCT serum concentrations were determined. The values of PCT serum concentrations and BISAP score were compared with values of CRP serum concentrations and APACHE II score, in relation to the severity and outcome of the disease. RESULTS: Values of PCT, CRP, BISAP score and APACHE II score, measured at 24 h of admission, were significantly elevated in patients with severe form of the disease. In predicting severity of AP at 24 h of admission, sensitivity and specificity of the BISAP score were 74% and 59%, respectively, APACHE II score 89% and 69%, respectively, CRP 75% and 86%, respectively, and PCT 86% and 63%, respectively. It was found that PCT is highly significant predictor of the disease outcome (p < 0,001). CONCLUSION: In early assessment of AP severity, PCT has better predictive value than CRP, and similar to the APACHE II score. APACHE II score is a stronger predictor of the disease severity than BISAP score. PCT is a good predictor of AP outcome.