Implementation of the Baveno Classification in Obstructive Sleep Apnea and Its Correlation with Symptoms of Anxiety and Depression.

Background and Objectives: The Baveno classification represents a new approach to the assessment of the severity of OSA (Obstructive sleep apnea), which takes significant comorbidities into account: atrial fibrillation, arterial hypertension, heart failure, stroke, diabetes mellitus, and OSA symptoms expressed through the Epworth sleepiness scale (ESS). The authors believe that the Baveno classification facilitates a better stratification of patients with OSA and can be a good guide for deciding on the therapeutic approach and clinical monitoring of patients with OSA, compared to the AHI (apnea-hypopnea index) itself. The aim of this paper is to confirm the advantage of applying the Baveno classification to the evaluation of symptoms of anxiety and depression in the OSA patients compared to the application of the AHI as a single parameter. Materials and Methods: This research represents an observational retrospective study that was performed at the Pulmonology Clinic of the University Clinical Center in Kragujevac, Serbia. The study sample included 104 patients with diagnosed OSA. Patients were divided into four categories retrogradely according to the Baveno classification (A, B, C, and D). Statistical data processing was performed using the IBM SPSS Statistics version 25.0 program. Results: In our study, we proved that the Baveno classification is better at predicting the depressive disorder in OSA patients compared to the AHI itself, according to abnormal BDI-II (Beck Depression Inventory) score (value greater than ten) and HADS-D (Hospital anxiety and depression) scale (value greater than eight). The average AHI in the entire group of examined patients was 44.3 ± 19.8, while in category A the average AHI was 25.2 ± 10, in category B, 53.4 ± 20.6; in category C, 38.2 ± 18.5; and in category D, 48.1 ± 19.2. In the total sample, AHI did not correlate with the depressive episodes, but individually, the highest frequency of the depressive symptoms was precisely in the categories with the highest AHI (group D and B), where more than half of the subjects had an abnormal score. The frequency of the anxiety disorder (HADS-A) between the analyzed groups did not differ significantly, although the largest number of patients with significant anxiety were in category B, according to the Baveno classification. Conclusions: We proved that the Baveno classification is applicable in real life, and it is better at evaluating anxiety and depression using questionnaires and can identify new patients who need CPAP therapy, independently of other OSAS symptoms, primarily daytime sleepiness.

Anthropometric Measurements and Admission Parameters as Predictors of Acute Respiratory Distress Syndrome in Hospitalized COVID-19 Patients.

Aim: We aimed to single out admission predictors of acute respiratory distress syndrome (ARDS) in hospitalized COVID-19 patients and investigate the role of bioelectrical impedance (BIA) measurements in ARDS development. Method: An observational, prospective cohort study was conducted on 407 consecutive COVID-19 patients hospitalized at the University Clinical Center Kragujevac between September 2021 and March 2022. Patients were followed during the hospitalization, and ARDS was observed as a primary endpoint. Body composition was assessed using the BMI, body fat percentage (BF%), and visceral fat (VF) via BIA. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis. Results: Patients with BMI above 30 kg/m2, very high BF%, and/or very high VF levels were at a significantly higher risk of developing ARDS compared to nonobese patients (OR: 4.568, 8.892, and 2.448, respectively). In addition, after performing multiple regression analysis, six admission predictors of ARDS were singled out: (1) very high BF (aOR 8.059), (2) SaO2 < 87.5 (aOR 5.120), (3) IL-6 > 59.75 (aOR 4.089), (4) low lymphocyte count (aOR 2.880), (5) female sex (aOR 2.290), and (6) age < 68.5 (aOR 1.976). Conclusion: Obesity is an important risk factor for the clinical deterioration of hospitalized COVID-19 patients. BF%, assessed through BIA measuring, was the strongest independent predictor of ARDS in hospitalized COVID-19 patients.

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Lung cancer is the most common cause of mortality from malignant tumors worldwide. The five-year survival rate for people with advanced stages varies considerably, from 35.4% to 6.9%. The angiogenic potential of bcl2 is not well known, nor is the way in which tumor cells with excessive bcl2 expression affect VEGF production. Hypothetically, given that tumor growth, progression and metastasis are dependent on angiogenesis, the antiapoptotic effect is expected to form a link between these two molecules. The aim of this study was to evaluate the relationship between bcl-2 and VEGF expression, clinicopathological features and survival in 216 patients with advanced NSCLC. Archival tumor tissues were examined by immunohistochemistry for the expression of bcl-2 and VEGF. Immunoreactivity for bcl-2 was observed in 41.4% of NSCLCs, 51% of squamous and 34.8% of adenocarcinomas-expressed Bcl-2. There was an inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (p < 0.0005). A total of 71.8% NSCLCs were VEGF positive, 56% of squamous and 82.2% of adenocarcinomas. High level of VEGF expression was significantly associated with histology type (p = 0.043), low histology grade (p = 0.014), clinical stage IV (p = 0.018), smoking history (p = 0.008) and EGFR mutations (p = 0.026). There was an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC patients (p = 0.039, r = -0.163). Two-year survival of patients with unresectable NSCLC was 39.3%, and 50% of patients were alive at 17 months. Our results demonstrated no difference in survival for patients in advanced NSCLC grouped by bcl-2 and VEGF status. Additionally, we observed an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC and mononuclear reaction and bcl-2 expression in adenocarcinomas.

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC.

Introduction: We present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC. Methods: Patients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mg/m2 (d 1) and 500 mg/m2 (d 8), cisplatin 75 mg/m2 (d 1), and gemcitabine 1250 mg/m2 (d 1 and 8) for four 3-week cycles, followed by avelumab 800 mg and cetuximab 500 mg/m2 every 2 weeks. The primary end point was the best overall response; the secondary end points were progression-free survival, duration of response, overall survival, and safety. Efficacy analyses were reported from an updated data cutoff. Results: A total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% [95% confidence interval: 21.0%-50.9%]), and the median duration of response was 7.1 months (95% confidence interval: 4.2-12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event. Conclusions: The combination of avelumab + cetuximab and chemotherapy showed antitumor activity and tolerable safety; however, the ORR was not improved compared with those reported for current standards of care (NCT03717155).

Admission Predictors of Mortality in Hospitalized COVID-19 Patients-A Serbian Cohort Study.

Background: Early prediction of COVID-19 patients' mortality risk may be beneficial in adequate triage and risk assessment. Therefore, we aimed to single out the independent morality predictors of hospitalized COVID-19 patients among parameters available on hospital admission. Methods: An observational, retrospective−prospective cohort study was conducted on 703 consecutive COVID-19 patients hospitalized in the University Clinical Center Kragujevac between September and December 2021. Patients were followed during the hospitalization, and in-hospital mortality was observed as a primary end-point. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis, including complete blood cell count, inflammation biomarkers and other biochemistry, coagulation parameters, and cardiac biomarkers. Socio-demographic and medical history data were obtained using patients' medical records. Results: The overall prevalence of mortality was 28.4% (n = 199). After performing multiple regression analysis on 20 parameters, according to the initial univariate analysis, only four independent variables gave statistically significant contributions to the model: SaO2 < 88.5 % (aOR 3.075), IL-6 > 74.6 pg/mL (aOR 2.389), LDH > 804.5 U/L (aOR 2.069) and age > 69.5 years (aOR 1.786). The C-index of the predicted probability calculated using this multivariate logistic model was 0.740 (p < 0.001). Conclusions: Parameters available on hospital admission can be beneficial in predicting COVID-19 mortality.

The Role of Bioelectrical Impedance Analysis in Predicting COVID-19 Outcome.

Background: Published data regarding the impact of obesity on COVID-19 outcomes are inconsistent. However, in most studies, body composition was assessed using body mass index (BMI) alone, thus neglecting the presence and distribution of adipose tissue. Therefore, we aimed to investigate the impact of body and visceral fat on COVID-19 outcomes. Methods: Observational, prospective cohort study included 216 consecutive COVID-19 patients hospitalized at University Clinical Center Kragujevac (Serbia) from October to December 2021. Body composition was assessed using the BMI, body fat percentage (%BF), and visceral fat (VF) via bioelectrical impedance analysis (BIA). In addition to anthropometric measurements, variables in the research were socio-demographic and medical history data, as well as admission inflammatory biomarkers. Primary end-points were fatal outcomes and intensive care unit (ICU) admission. Results: The overall prevalence of obesity was 39.3% according to BMI and 50.9% according to % BF, while 38.4% of patients had very high VF levels. After adjusting odds ratio values for cofounding variables and obesity-related conditions, all three anthropometric parameters were significant predictors of primary end-points. However, we note that % BF and VF, compared to BMI, were stronger predictors of both mortality (aOR 3.353, aOR 3.05, and aOR 2.387, respectively) and ICU admission [adjusted odds ratio (aOR) 7.141, aOR 3.424, and aOR 3.133, respectively]. Conclusion: Obesity is linked with COVID-19 mortality and ICU admission, with BIA measurements being stronger predictors of outcome compared to BMI use alone.

SARS-CoV-2 infection induces mixed M1/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets.

Clinical manifestations of SARS-CoV-2 infection range from mild to critically severe. The aim of the study was to highlight the immunological events associated with the severity of SARS-CoV-2 infection, with an emphasis on cells of innate immunity. Thirty COVID-19 patients with mild/moderate symptoms and 27 patients with severe/critically severe symptoms were recruited from the Clinical Center of Kragujevac during April 2020. Flow cytometric analysis was performed to reveal phenotypic and functional alterations of peripheral blood cells and to correlate them with the severity of the disease. In severe cases, the number of T and B lymphocytes, dendritic cells, NK cells, and HLA-DR-expressing cells was drastically decreased. In the monocyte population proportion between certain subsets was disturbed and cells coexpressing markers of M1 and M2 monocytes were found in intermediate and non-classical subsets. In mild cases decline in lymphocyte number was less pronounced and innate immunity was preserved as indicated by an increased number of myeloid and activated dendritic cells, NK cells that expressed activation marker at the same level as in control and by low expression of M2 marker in monocyte population. In patients with severe disease, both innate and adoptive immunity are devastated, while in patients with mild symptoms decline in lymphocyte number is lesser, and the innate immunity is preserved.

Relationship between incidence of chronic obstructive pulmonary disease and lung cancer as comorbidity in primary health care in two Belgrade communities.

PURPOSE: To investigate the recent trends in the incidence of chronic obstructive pulmonary disease (COPD) and lung cancer as comorbidity in primary health care (Community Health Center, Zemun, Belgrade, which covers two municipalities - Surchin and Zemun), during the period 2014-2017. METHODS: This retrospective study analyzed the incidence of COPD and lung cancer as comorbidity in a 4-year period. Data were derived from the Heliant information system. Descriptive statistics -frequencies and percentages - were used, and differences between groups were tested by x2 test. RESULTS: The number of patients with COPD was slightly, but insignificantly, higher each consecutive year. Lung cancer as comorbidity appeared in about 11% of these patients. As for gender, male and female patients contributed equally to the number of patients with CORD. CONCLUSION: The number of patients with COPD registered in primary health care was similar in all investigated years. Lung cancer as comorbidity was found in a significantly smaller number of these patients.

Appearance of ductal breast and colon carcinoma with gastrointestinal stromal tumor (GIST) in a female patient: an extremely rare case.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Very few cases of coexistence of GIST and adenocarcinoma in other organs have been described. CASE PRESENTATION: We present the case of a 63-year-old female patient diagnosed with breast cancer. After five years of the diagnosis, the findings of colon adenocarcinoma and GIST in stage IA were discovered incidentally during surgical treatment of the colon carcinoma. This tumor display: mixed spindle-epithelioid cell cytological type, of moderate cellularity, mitotic index (1∕10) with low anaplasia, low proliferative status (Ki-67 index 12%), without necrosis and immunophenotype profile: antiendomysial antibody (EMA)-, vimentin+++, CD117++, CD34+++, alpha-smooth muscle actin (α-SMA)+, desmin+∕-, S-100-, CD68-. CONCLUSIONS: The present case is extremely rare since the patient has adenocarcinoma with GIST in a previously diagnosed breast carcinoma. Based on this, in clinical practice should always think about possibility occurrence of synchronous and metachronous tumors.

The relation between nonspecific hyperreactivity of the airways and atopic constitution in asthmatics.

Background/Aim: Hyperreactivity of the airways caused by inflammation in asthmatics is the most important pathophysiological change. It represents a suitable ground that in the presence of risk factors and the drivers of asthma, asthmatic attack occurs. Atopic constitution is one of the most important risk factors for the development and expression of asthma. The aim of our study was to investigate the relationship between nonspecific airway hyperreactivity and atopic constituton in asthmatics. Methods: This retrospective analysis was conducted considering the results of nonspecific bronchoprovocative test with histamine, skin tests to inhalant allergens and total IgE levels in the serum of asthmatic patients with controlled bronchial asthma. The sample consisted of 162 asthmatics examined during one-year period. Results: The examinees were male asthmatic patients, aged between 18 and 30 years. We found that the examinees with a pronounced non-specific hyperreactivity had more significant skin reaction to inhaled allergens and higher levels of total IgE in serum. Conclusion: The results of our study show that the intensity of airway hyperresponsiveness to histamine in asthmatics is directly related to atopic constitution.

Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity.

OBJECTIVE: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. METHODS: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. RESULTS: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. CONCLUSIONS: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe.

OBJETIVO: Avaliar os custos médicos diretos e indiretos de diagnóstico e tratamento para pacientes com pneumonia adquirida na comunidade (PAC), correlacionando-os com a gravidade da PAC ao diagnóstico e identificando os principais fatores de custo. MÉTODOS: Análise de custos prospectiva utilizando custo bottom-up. A gravidade clínica e o risco de mortalidade foram determinados através de pneumonia severity index (PSI) e a escala mentalConfusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65), respectivamente. A amostra foi composta por 95 pacientes hospitalizados devido a PAC recém-diagnosticada. A análise foi realizada em uma perspectiva social com um horizonte de tempo de um ano. RESULTADOS: Expressos em média ± desvio-padrão em euros, os custos médicos diretos e indiretos por paciente com PAC foram de 696 ± 531 e 410 ± 283, respectivamente, sendo, portanto, o custo total por paciente de 1.106 ± 657. O impacto orçamentário combinado deste grupo de pacientes em euros foi de 105.087 (66.109 e 38.979 nos custos diretos e indiretos, respectivamente). Os principais fatores de custo, em ordem descendente, foram custo de oportunidade (perda de produtividade); diagnóstico e tratamento de comorbidades; e administração de medicamentos, oxigênio e derivados do sangue. Os escores CURB-65 e PSI correlacionaram-se com os custos indiretos do tratamento da PAC. O escore PSI correlacionou-se positivamente com a frequência global no uso de serviços médicos. Nenhum dos escores mostrou uma relação clara com os custos diretos do tratamento da PAC. CONCLUSÕES: A gravidade clínica na admissão parece não se correlacionar com os custos do tratamento da PAC. Esses custos são principalmente causados por internações hospitalares desnecessárias (ou por internação desnecessariamente prolongada) em casos de pneumonia leve, assim como pela prescrição exagerada de antibióticos. As autoridades devem se esforçar para melhorar a adesão às diretrizes e promover práticas de prescrição custo-efetivas entre os médicos do sudeste da Europa.

Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity, / Pneumonia adquirida na comunidade: economia de cuidados médicos, em relação à gravidade clínica

Objective: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. Methods: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. Results: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. Conclusions: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe. .

Objetivo: Avaliar os custos médicos diretos e indiretos de diagnóstico e tratamento para pacientes com pneumonia adquirida na comunidade (PAC), correlacionando-os com a gravidade da PAC ao diagnóstico e identificando os principais fatores de custo. Métodos: Análise de custos prospectiva utilizando custo bottom-up. A gravidade clínica e o risco de mortalidade foram determinados através de pneumonia severity index (PSI) e a escala mental C onfusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65), respectivamente. A amostra foi composta por 95 pacientes hospitalizados devido a PAC recém-diagnosticada. A análise foi realizada em uma perspectiva social com um horizonte de tempo de um ano. Resultados: Expressos em média ± desvio-padrão em euros, os custos médicos diretos e indiretos por paciente com PAC foram de 696 ± 531 e 410 ± 283, respectivamente, sendo, portanto, o custo total por paciente de 1.106 ± 657. O impacto orçamentário combinado deste grupo de pacientes em euros foi de 105.087 (66.109 e 38.979 nos custos diretos e indiretos, respectivamente). Os principais fatores de custo, em ordem descendente, foram custo de oportunidade (perda de produtividade); diagnóstico e tratamento de comorbidades; e administração de medicamentos, oxigênio e derivados do sangue. Os escores CURB-65 e PSI correlacionaram-se com os custos indiretos do tratamento da PAC. O escore PSI correlacionou-se positivamente com a frequência global no uso de serviços médicos. Nenhum dos escores mostrou uma relação clara com os custos diretos do tratamento da PAC. Conclusões: A gravidade clínica na admissão parece não se correlacionar com os custos do tratamento da PAC. Esses custos são principalmente causados por internações hospitalares desnecessárias (ou por internação desnecessariamente prolongada) em casos de pneumonia leve, assim como pela prescrição exagerada de antibióticos. As autoridades devem se esforçar para melhorar a adesão às diretrizes ...

ECTOPIC ACTH SECRETION WITH CONCOMITANT HYPERAMYLASEMIA IN A PATIENT WITH SMALL CELL LUNG CARCINOMA: CASE REPORT.

Histologically confirmed small cell lung cancer associated with Cushing's syndrome and elevated amylase is rarely described in the literature. We present a case of a 63-year-old patient admitted to cardiology department due to shortness of breath, exhaustion, palpitations and nausea. Elevated values of troponin and electrocardiography suggested that he could have acute coronary syndrome. According to the radiologist's opinion, plane lung radiography was normal. Elevated level of amylase was found in both serum (3802 U/L, normal range 28-100) and urine (12012 U/L, normal range 0-450 U/L), as well as elevated sodium (156 mmol/L, normal range 137-147 mmol/L), hyperglycemia (12 mmol/L, normal range 3.8-6.1 mmol/L) and lowered serum potassium (1.7 mmol/L, normal range 3.5-5.3 mmol/L). Computerized tomography (CT) of the abdomen revealed a tumor of the left adrenal gland and enlargement of the right adrenal gland with normal structure of the pancreas. During hospitalization, the patient had blood while coughing and CT scan of the lungs showed a tumor 48x38x51 mm in size localized in the laterobasal segment of the left lung with mediastinal lymphadenopathy. He also had bilateral pleural effusions with signs of pulmonary embolism, which explained elevated troponin values. Biopsy confirmed microcellular lung carcinoma and tumor cells were diffusely positive for TTF-1 and focally for CK7, expressing markers of neuroendocrine differentiation (chromogranin +++, synaptophysin +++, NSE ++). Since neuroendocrine tumor was confirmed and the patient had low potassium and high glucose, hypercortisolism was suspected. High morning cortisol (1784 mmol/L, normal range 171-536) and unsuppressed ACTH (214 pg/L, < 60), as well as a high level of chromogranin (1339 µg/L, < 65) were determined. During hospital stay, the patient developed heart and respiratory failure and died in the second week of hospitalization.

The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer.

Lung cancer is the most common cancer, and small-cell lung cancer (SCLC) accounts for around 20 % of lung cancers. SCLC has a neuroendocrine cellular origin, and the tumor cells usually express neuroendocrine markers. There have been major recent advances in the management of SCLC, and multimodal approaches are now the norm. An improved knowledge of the prognostic variables would assist in defining which patients were better candidates to receive these newer intensive therapies. This single-center retrospective study of 97 previously untreated and histologically proven SCLC patients analysed the circulating neuroendocrine markers chromogranin A (CGA), pro-gastrin-releasing peptide (ProGRP), and neuron-specific enolase (NSE) in addition to the other more classical variables. Fifty patients had limited-stage disease and 47 had extensive disease. Sixty patients had an ECOG performance status (PS) of 0-1 and 37 had PS 2-4. Median survival for the whole study population was 13 months. Univariate analysis and univariate Cox regression modeling found a statistically significant association between survival and PS, disease stage, and CGA, ProGRP, and NSE levels. Age and sex were not prognostic. A shorter survival time was found in patients with a PS equal to or >2, extensive stage disease, a serum CGA level >56 ng/ml, a serum ProGRP level >58 pg/ml, and a serum NSE level >19 ng/ml. This study has found that there is a potential role for ProGRP, NSE, and CGA in both staging and prognosing survival in SCLC patients.

NT-proBNP for prognostic and diagnostic evaluation in patients with acute coronary syndromes.

BACKGROUND AND AIM: N terminal-proB-type natriuretic peptide (NT-proBNP) is synthesised and secreted from the ventricular myocardium. This marker is known to be elevated in patients with acute coronary syndromes (ACS). We evaluated NT-proBNP asa significant diagnostic marker and an important independent predictor of short-term mortality (one month) in patients with ACS. METHODS: NT-proBNP and cardiac troponin I (cTI) were assessed in 134 consecutive patients (median age 66 years, 73% male)hospitalised for ACS in a cardiological university department. The patients were classified into ST-elevation ACS (STE-ACS, n = 74) and non-ST-elevation ACS (NSTE-ACS, n = 60) groups based on the ECG findings on admission. Patients with Killip class ≥ II were excluded. RESULTS: The serum level of NT-proBNP on admission was significantly higher (p < 0.0005), while there was no difference in cTI serum level in the NSTE-ACS patients compared to STE-ACS patients. There was a significant positive correlation between NT-proBNP and cTI in the NSTE-ACS (r = 0.338, p = 0.008) and STE-ACS (r = 0.441, p < 0.0005) patients. There was a significant difference in NT-proBNP (p < 0.0005) and cTI (p < 0.0005) serum level between ACS patients who died within 30 days or who survived after one month. The increased NT-proBNP level is the strongest predictor of mortality in ACS patients, also NT-proBNP cut-point level of 1,490 pg/mL is a significant independent predictor of mortality. CONCLUSIONS: We demonstrated the differences and the correlation in the secretion of NT-proBNP and cTI in patients with STE-ACS vs. NSTE-ACS. Our results provide evidence that NT-proBNP is a significant diagnostic marker and an important independent predictor of short-term mortality in patients with ACS.

Risk factors for brain metastases in surgically staged IIIA non-small cell lung cancer patients treated with surgery, radiotherapy and chemotherapy.

INTRODUCTION/AIM: Lung cancer is a leading cause of mortality among patients with carcinomas. The aim of this study was to point out risk factors for brain metastases (BM) appearance in patients with IIIA (N2) stage of nonsmall cell lung cancer (NSCLC) treated with three-modal therapy. METHODS: We analyzed data obtained from 107 patients with IIIA (N2) stage of NSCLC treated surgically with neoadjuvant therapy. The frequency of brain metastases was examined regarding age, sex, histological type and the size of tumor, nodal status, the sequence of radiotherapy and chemotherapy application and the type of chemotherapy. RESULTS: Two and 3-year incidence rates of BM were 35% and 46%, respectively. Forty-six percent of the patients recurred in the brain as their first failure in the period of three years. Histologically, the patients with nonsquamous cell lung carcinoma had significantly higher frequency of metastases in the brain compared with the group of squamous cell lung carcinoma (46%:30%; p = 0.021). Examining treatment-related parameters, treatment with taxane-platinum containing regimens was associated with a lower risk of brain metastases, than platinum-etoposide chemotherapy regimens (31%:52%; p = 0.011). Preoperative radiotherapy, with or without postoperative treatment, showed lower rate of metastases in the brain compared with postoperative radiotherapy treatment only (33%:48%; p = 0.035). CONCLUSION: Brain metastases are often site of recurrence in patients with NSCLC (IIIA-N2). Autonomous risk factors for brain metastases in this group of patients are non-squamous NSCLC, N1-N2 nodal status, postoperative radiotherapy without preoperative radiotherapy.

[Clinical manifestations of atopy in children up to two years of age].

BACKGROUND/AIM: Atopic diseases such as atopic dermatitis, allergic rhinitis and asthma have had increased prevalence during the past decade and nowadays occur in every third child in developed countries. The aim of the study was to determine frequency and type of atopic diseases at the age of two, as well as the importance the total IgE antibodies concentrations have in diagnosis and prognosis of the disease. METHODS: The study involved 175 children up to two years of age. Allergy-like symptoms were found after surveying their parents and pediatric medical records. Using the fluorescence immunossay (FIA) method, total IgE antibodies concentrations and specific IgE antibodies (Phadiatop infant) were determined on an Immunocap 100 Dyagnostic System. RESULTS: One or more allergy-like symptoms accounted for 57.7% of findings in children under the age of two, whilst in 19.4% the existence of IgE-related allergic diseases was found. Atopic diseases usually have clinical manifestations of atopic dermatitis (11.4%), IgE-bound wheezing/asthma (10.8%) and food allergies (7.4%), and to much lesser extent those of allergic rhinitis (3.4%) and urticaria (1.7%). The significantly higher total IgE antibodies concentrations were found in children with allergy-like symptoms (p < 0.0005) (cut-off 15.15 kU/L, sensitivity 76.5% specificity 71.6%). CONCLUSION: Almost 20% of two-year-old children have any of clinically manifested allergic diseases, with atopic dermatitis and IgE wheeze/asthma being predominant. The higher total IgE antibodies concentration is a good marker for sensitization in children with allergy-like symptoms.

Neuroendocrine differentiation as an indicator of chemosensitivity and prognosis in nonsmall cell lung cancer.

CONTEXT: Nonsmall cell lung cancers with neuroendocrine differentiation (NSCLC-ND) may demonstrate biologic behavior intermediate between NSCLC and small cell lung cancer (SCLC) with impact on prognosis. METHODS: We analyzed 116 consecutive patients with Stage III and IV NSCLC who were diagnosed and treated between 2001 and 2006. Using immuno-histochemical staining for neuron-specific enolase (NSE), chromogranin A (ChrA), and synaptophysin (Syn), 29 (25%) NSCLC-ND were identified. RESULTS: Expression of NSE was present in 22.4%, ChrA in 15.5% and Syn in 14.8% of patients with NSCLC. Therapeutic response was significantly better in the NSCLC-ND group and specimens with > 30% neuroendocrine (NE)-differentiated tumor cells showed favourable therapeutic response (P < 0.05). Multivariate binary logistic regression showed that percentage of NE positive tumor cells was a significant independent prognostic factor associated with a favourable outcome. Receiver operating characteristic (ROC) curves and areas under ROC curves confirmed that percentage of NE-differentiated tumor cells could be useful prediction factor of therapeutic response. Moreover, according to percentage of NE-differentiated tumor cells, optimal cutoffs and related sensitivities and specificities were determined for each markers. CONCLUSION: Advanced-stage NSCLC with NE tumor cells are clinically less aggressive tumors. Percentage of NE-differentiated tumor cells identifies patients with favourable therapy response to paclitaxel-cisplatin.

[Body mass index in asthmatic children before and after one year inhaled glucocorticosteroids therapy BMI].

INTRODUCTION: Asthma is the most frequent children's disease, with a tendency of further growth. Bearing in mind controversial data on obesity of asthmatic children and a possible effect of inhaled corticosteroids (ICS) on children's growth, the aim of our study was to determine the body mass index (BMI) in asthmatic children at the beginning of the therapy and to study the effect of the continuous application of ICS on growth and BMI during the period of 1 year. MATERIAL AND METHODS: The study included 100 children aged 7 to 18 diagnosed to have partly controlled and uncontrolled allergic asthma, who were continuously given ICS as a prevention against asthma attacks at Pediatric Clinic of the Clinical Center in Kragujevac for the period of 1 year. Children with BMI < p10 by their age and gender were considered to be underweight, children with p10-84 as of normal weight, children with p85-97 as overweight and children with BMI > p97 as obese. RESULTS: The highest percentage of children with asthma was within normal parameters (70%), 10% of the children were underweight (boys: n = 8/60, 13.3% vs. girls: n = 2/40, 5%), and 18% were overweight/obese. Monovariable analysis of variant with repeated measurements have shown a statistically significant difference in the height of children in all age groups after a year of continuous therapy of ICS (p = 0.000), except in girls aged 15-18, who did not show any significant difference in body height after the therapy (p > 0.05). CONCLUSION: Asthmatic children with partly controlled and uncontrolled asthma have mostly normal BMI and ICS can be safely administered in asthmatic children.

[The value of neuroendocrine markers for response to therapy and survival in patients with advanced non-small cell lung cancer].

INTRODUCTION: Non-small cell lung cancer (NSCLC) accounts for about 70-80% of all lung cancers. In comparison with small cell lung cancer, NSCLC has relatively low therapy response. Discovery of neuroendocrine markers within the NSCLC group (10-30%) has initiated the issue of their importance in the therapy and prognosis. OBJECTIVE: The aim of this study was to determine the influence of neuroendocrine differentiation on treatment response and survival in patients with advanced NSCLC. METHODS: A clinical trial included 236 patients (73.7% males), with diagnosis of NSCLC, determined by histological verification. These patients were treated by combined chemo- and X-ray therapy at stage III (without pleural effusion) or chemotherapy only at stage III (with pleural effusion) and stage IV of NSCLC. When the progression had been noted at the stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron-specific enolase (NSE), chromogranin A (ChrA) as well as synapthophysin (SYN) expression in tissue examples was determined by immunohistochemical analysis with monoclonal mouse anti human bodies (DAKO Comp, Denmark). The treatment was conducted during 4 to 6 chemotherapeutic cycles. The efficacy was assessed after the therapy regimen; median survival time was assessed after the randomization. RESULTS: NSE, ChrA and SYN expression were noted in 56 (23.7%), 33 (13.9%) and 39 (16.5%) patients, respectively. Better therapeutic response was significantly higher in patients with expression of NSE, ChrA and SYN (p < 0.05). There was significant correlation between therapy response and the percentage of positive tumour cells with neuroendocrine differentiation (p < 0.05). The one-year and two-year follow-up survival period in patients with neuroendocrine expression was 64% (without expression 28%; p < 0.001) and 30% (p = 0.000). CONCLUSION: Tissue expression of neuroendocrine markers influences greatly a therapeutic response in patients with advanced stage of NSCLC. Better therapeutic response was recorded in patients with possitive expression of neuroendocrine markers and higher percentage of positive tumour cells. Median survival time is higher in patients in Ill or IV stage of NSCLC, when neuroendocrine markers are expressed.