Association of soluble ST2 with functional capacity in outpatients with heart failure.

BACKGROUND: Biomarkers play an important role in the risk stratification of patients with heart failure (HF). Recent studies have shown that soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin 1 receptor family, is associated with disease prognosis in acute and chronic HF. In this study we aimed to investigate the relation between sST2 level and functional capacity in outpatients with systolic HF. PATIENTS AND METHODS: This study included 120 HF patients with reduced ejection fraction (HFrEF; EF ≤ 40%). The mean age of patients was 66 ± 11 years. Advanced HF (New York Heart Association [NYHA] functional class III-IV) was observed in 35 patients (29%). RESULTS: sST2 levels were on average higher in patients with NYHA functional classes III and IV than in patients with NYHA functional classes I and II (51 [9-198] vs. 25 ng/ml [9-118], p < 0.001). In a multiple logistic regression model, sST2 level (OR: 1.044, p = 0.004, 95% CI: 1.014-1.075), hemoglobin level (OR: 0.590, p = 0.001, 95% CI: 0.433-0.805), total cholesterol level (OR: 0.977, p = 0.004, 95% CI: 0.962-0.993), and age (OR: 1.066, p = 0.047, 95% CI: 1.001-1.136) were associated with poor functional capacity. In receiver operating characteristic (ROC) curve analysis, the optimal cut-off value of sST2 for predicting poor functional capacity was >42 ng/ml, with 63% sensitivity and 88% specificity (AUC: 0.810, 95% CI: 0.728- 0.875). CONCLUSION: Higher sST2 levels were strongly associated with poor NYHA functional class, independent of cardiac risk factors, in outpatients with HFrEF.

Influence of influenza vaccination on recurrent hospitalization in patients with heart failure.

BACKGROUND: The current study aimed to evaluate the influence of regular annual influenza vaccinations on cardiovascular (CV) death and heart failure-related hospitalizations (HFrH) in stable outpatients with heart failure with reduced ejection fraction. METHODS: The Turkish research team-HF (TREAT-HF) is a network undertaking multicenter, observational cohort studies in HF. This study is a subgroup analysis of TREAT-HF outpatient cohorts who completed a questionnaire on influenza vaccination status and for whom follow-up data were available. A total of 656 patients with available follow-up data for CV death and HFrH including recurrent hospitalization were included in the study. Patients were classified into two groups: those who received regular influenza vaccination (40 %) and those who did not receive vaccination. RESULTS: During a mean follow-up of 15 ±6 months, 113 (18 %) patients had CV death and 471 (72 %) patients had at least one HFrH. The CV death rate was similar in both groups of patients (16 vs. 19 %, p = 0.37), whereas, HFrH and recurrent HFrH were significantly less frequently encountered in patients who received regular influenza vaccination than in those who did not receive vaccination (43 vs. 92 % and 16 vs. 66 %, p < 0.001, respectively). In a multivariate Cox proportional hazards model - in addition to a few clinical factors - vaccination status (HR = 0.30, 95 % CI = 0.17-0.51, p < 0.001) and graduation from university (HR = 0.35, 95 % CI = 0.17-0.72, p = 0.004) remained independently associated with the risk of recurrent HFrH. CONCLUSION: Regular influenza vaccination does not influence CV deaths; however, it decreases HFrH including recurrent episodes of HFrH in outpatients with heart failure with reduced ejection fraction.

Cancer antigen 125 levels and increased risk of new-onset atrial fibrillation.

OBJECTIVE: Elevated cancer antigen 125 (CA-125) levels are associated with cardiopulmonary disorders such as acute and chronic heart failure (HF), coronary artery disease, chronic obstructive pulmonary disease, and atrial fibrillation (AF). The development of atrial fibrillation (AF) is related to morbidity and mortality in patients with HF: therefore, it is important to identify patients with increased risk for development of AF. We investigated whether plasma CA-125 levels in patients with hospitalized systolic HF could predict the development of AF. PATIENTS AND METHODS: A total of 149 consecutive patients with sinus rhythm who were admitted to the emergency department with hospitalized systolic HF were evaluated prospectively. Serum CA-125 levels were obtained after initial stabilization during their hospital stay. RESULTS: AF developed in 36 (% 24.2) patients during a follow-up period of 22.1 ± 11  months (range 3-61). CA-125 levels were significantly higher in patients who developed AF than in patients with sinus rhythm [99 U/ml (48-172) vs. 47 U/ml (18-108), p = 0.001]. The optimal cut-off level of CA-125 to predict development of AF was found to be > 68.49 U/ml. CA-125 > 68.49 U/ml, left atrial diameter, right ventricular dilatation, moderate to severe mitral and tricuspid regurgitations were found to have prognostic significance in univariate analysis. In a multivariate Cox proportional hazards model with the backward stepwise method, CA-125 > 68.49 U/ml (HR = 2.693, % 95 CI = 1.285-5.641, p = 0.009) and moderate to severe mitral regurgitation (HR = 2.708, % 95 CI = 1.295-5.663, p = 0.008) were associated with an increased risk of new-onset AF after adjustment for variables found to be statistically significant in univariate analysis and correlated with CA-125 level. CONCLUSION: CA-125 level is associated with the development of AF in patients with hospitalized systolic HF.

Significant correlation between uric acid levels and flow-mediated dilatation in patients with masked hypertension.

BACKGROUND: Serum uric acid (UA) level is associated with prognosis in cardiovascular disorders such as sustained hypertension, diabetes mellitus and chronic kidney diseases. Increased UA levels in sustained hypertension may reflect early renal vascular alterations. However, it remains unclear if serum UA is associated with endothelial dysfunction in masked hypertensive patients. METHODS: A total of 100 individuals (57% men and 43% women; mean 45 ± 8 years) with masked hypertension were included in the present study. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. RESULTS: Univariate regression analysis showed that the FMD was significantly negative correlated with uric acid (r = -0.300, p = 0.002), ambulatory 24-h systolic blood pressure (SBP) (r = -0.275, p = 0.008), hs-CRP (r = -0.222, p = 0.033) and diastolic aortic diameter (r = -0.243, p = 0.019). In multivariate linear regression analysis, only uric acid levels and ambulatory 24-h SBP were significantly associated with FMD. CONCLUSION: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.

A high oxidative stress index predicts endothelial dysfunction in young male smokers.

Experimental studies have shown that smoking was related to endothelial dysfunction via oxidative stress. However, the degree of oxidative stress to be associated with endothelial dysfunction is unknown. Oxidative stress index (OSI) might be a useful and easy way of determining the endothelial dysfunction. Hence, we aimed to evaluate the relationship between OSI and flow mediated dilatation (FMD) in smoking healthy male volunteers. Eighty smoking healthy male volunteers were enrolled in the study. Participants were classified as having normal and abnormal FMD response. In an univariate analysis; systolic and diastolic blood pressures, C-reactive protein (CRP), low-density lipoprotein cholesterol, OSI and lipid peroxidation (LPO) levels were predictive for abnormal FMD response. In a multivariable logistic regression analysis with forward stepwise method, OSI (OR: 3.194, 95% CI: 1.710-5.966, p<0.001) and CRP (OR: 2.082, 95% CI: 1.101-3.939, p 0.024) were found to be independent parameters for predicting abnormal FMD response in young male smokers. The optimal cut-off value of OSI for detecting abnormal FMD response was found to be >3.35, with 100 % sensitivity and 84.1 % specificity. We have shown that critical endothelial dysfunction can easily be detected by OSI in individuals, at risk for developing coronary artery disease, such as smokers (Tab. 3, Fig. 3, Ref. 30). Text in PDF www.elis.sk.

Acute heart failure with accompanying chronic obstructive pulmonary disease: should we focus on beta blockers?

BACKGROUND: Acute heart failure (AHF) with systolic dysfunction is associated with increased morbidity and mortality, and optimal therapy is not well established, despite the findings of evidence-based medicine. Beta blockers provide a mortality and morbidity benefit in patients with chronic systolic HF, and are currently indicated in all stages of patients with systolic HF. We evaluated therapies before discharge, in particular beta blockers, in patients hospitalized with AHF with and without accompanying chronic obstructive pulmonary disease (COPD). METHODS: The hospital discharge records of 959 consecutive de novo AHF patients, hospitalized and treated for systolic HF (ejection fraction < 45%), were retrospectively reviewed in three cardiovascular institutions. RESULTS: The presence of accompanying COPD was associated with significantly lower prescription of beta blockers before discharge (p < 0.001). Furthermore, with regard to the type of beta blocker, patients with accompanying COPD were less frequently prescribed nonselective beta blockers (29% vs. 48%, p < 0.001). The presence of accompanying COPD among AHF patients increased the risk of omitting (not prescribing) beta blockers before discharge by a factor of 1.785. CONCLUSION: Beta blockers, a proven life-saving therapy in the setting of chronic systolic HF, were found to be less frequently prescribed before discharge in the presence of de novo AHF with accompanying COPD.

Second line palliative endobronchial radiotherapy with HDR Ir 192 in recurrent lung carcinoma.

PURPOSE: To observe the efficiency of reirradiation with high dose rate intraluminal brachytherapy in symptomatic palliation of recurrent endobronchial tumors. MATERIALS AND METHODS: Between January 1994 and June 1998, 21 patients diagnosed with recurrent endobronchial tumors following external beam radiotherapy were treated palliatively with high dose rate intraluminal irradiation at Hacettepe University Oncology Institute. A single fraction of 10 Gy was prescribed to the specified area in 9 patients and 15 Gy to 12. RESULTS: Endobronchial treatment improved the performance and reduced symptomatology in 17 (81%) patients. Ten dyspneic patients (10/14, 71%) recovered clinically with an accompanying radiological downstaging. The median symptomatic palliation was 45 days (range, 0-9 months), and the overall median survival was 5.5 months (range, 4-12 months). The palliative intrabronchial brachytherapy was well tolerated, with the exception of in one patient with a fatal hemorrhage, and another with medically salvaged bronchospasm and intrabronchial edema. CONCLUSION: Recurrent patients with a history of previous thoracic external beam irradiation can be effectively palliated with high dose rate endobronchial reirradiation if the symptoms are directly related to the endobronchial tumor.

Protective effects of melatonin on the ionizing radiation induced DNA damage in the rat brain.

Melatonin is an endogenously produced antioxidant with radioprotective actions while ionizing radiation is a well-known cytotoxic and mutagenic agent of which the biological results are attributable to its free radical producing effects. The effect of melatonin on the DNA strand breakage and lipid peroxidation induced by ionizing radiation in the rat brain were investigated in order to clarify its radioprotective ability. The DNA strand breakage in rat brain exposed to 1000 cGy ionizing radiation was assessed by alkaline single cell gel electrophoresis and the lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) concentrations. A significant increase in DNA damage (p < 0.05) and TBARS concentrations (p < 0.01) was found in the radiation treated rat brain. Pre-treatment of rats with intraperitoneal doses of 100 mg/kg melatonin provided a significant decrease in the DNA strand breakage and lipid peroxidation. Our results indicate that melatonin can protect brain cells from oxidative damage induced by ionizing radiation.

Reverse seeding of recurrent intraspinal malignant meningioma.

Meningiomas are common intracranial and intraspinal tumors and constitute 15-20% of all primary brain tumors. Ten to 15% of all meningiomas are considered malignant. The main treatment of meningiomas is surgical resection. Meningioma recurrence following surgery is frequent. However, it is not clear whether recurrent meningiomas, close or distant to the primary resection site, arise from incomplete resection, dissemination of tumor fragments or from independent tumor growth. We herein describe a 40-year-old woman with intraspinal malignant meningioma recurring each time upwards, i.e. apparently by reverse way of seeding, via cerebrospinal fluid.

Malignancy in Behçet's disease: a report of 13 cases and a review of the literature.

Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.

Accelerated hyperfractionated radiotherapy in supratentorial malignant astrocytomas.

PURPOSE: To determine the safety and effectiveness of accelerated hyperfractionated radiotherapy in the treatment of supratentorial malignant astrocytomas. MATERIALS AND METHODS: Between June 1995-July 1997, 75 patients were enrolled to a prospective phase II study. A total dose of 60 Gy was delivered in 2 Gy b.i.d. fractions with an interval of 6-8 h, 5 days per week, in an overall time of 3 weeks. The treatment protocol was planned to give 40 Gy to a treatment volume covering the contrast-enhancing lesion and oedema (+ 3-cm margin) and additional 20 Gy to the volume encompassing the contrast-enhancing lesion alone with a 1-cm margin based on preoperative magnetic resonance imaging and/or CT findings. The patients had a median age of 46 years and a median Karnofsky performance status score of 80. Histology consisted of anaplastic astrocytoma (AA) in 16 (21%) and glioblastoma multiforme (GBM) in 59 (79%) patients. RESULTS: Median survival was 11 months for all patients; 10 months for GBM patients and 40 months for AA patients. Survival rates at 1 and 3 years were 41%, 11% for all patients; 62, 37% for AA patients and 35, 6% for GBM patients, respectively. Multivariate analysis revealed significant impact of age, histology and neurological functional class on survival. The incidence of grade 3 or worse late neurological toxicity was 5.3%. CONCLUSIONS: Although accelerated hyperfractionated radiotherapy showed no significant advantage on survival, it shortened the treatment period from 6 to 3 weeks. Radiotherapy was well tolerated and the incidence of late toxicity is acceptable.

Use of the alkaline comet assay to monitor DNA damage in technicians exposed to low-dose radiation.

The exposure of human beings to ionizing radiation is still of great concern in occupational and environmental medicine, and the widespread use of radiotherapy in the treatment of cancer has led to anxiety about the possible hazards to staff who are at risk of such occupational exposure. In this study, DNA damage in the peripheral lymphocytes of 30 technicians employed in radiation oncology departments for at least 1 year were examined by the alkaline single-cell gel electrophoresis "comet" technique. The results were compared with those of 30 controls with comparable age, sex, and smoking habits who were not working in radiation oncology or chemotherapy services. The DNA damage observed in the lymphocytes of the technicians was significantly higher than that in the controls (P < 0.001). Cigarette smoking was also related to increases in DNA damage, and a significant association was found between the duration of occupational exposure to low-dose ionizing radiation and the DNA damage.

Intracranial ependymomas: treatment results and prognostic factors.

Forty-nine intracranial ependymoma patients were postoperatively irradiated with craniospinal, cranial, or wide local fields. Thirty-two patients received an adjuvant chemotherapy regimen of vincristine and CCNU with or without procarbazine. The 10-year actuarial overall and progression-free survival rates were 57% and 57%, respectively. Age was the only significant prognostic factor in favor of adults (p = 0.01).

Cranial nerve involvement in nasopharyngeal carcinoma: its prognostic role and response to radiotherapy.

Between 1975 and 1989, 23 nasopharyngeal carcinoma patients presenting with cranial nerve involvement (CNI) of one or more nerves at the time of diagnosis were treated and followed-up in our department. All patients were irradiated with curative intent, and total doses of 50 to 70 Gy (median 65 Gy) were delivered to the nasopharynx. Cranial nerves VI, III, V, IV, IX, and XII were the most commonly involved nerves. The total response rate of cranial nerves was 74% in a median follow-up time of 2 years, with the highest rate observed in the third and sixth cranial nerves. All complete responses except two were observed in the first month after radiotherapy.

Does gastric adenocarcinoma develop after the treatment of gastric lymphoma?

Two adult patients with the diagnosis of gastric lymphoma who developed adenocarcinoma of the stomach 8 years after the treatment are presented. Both patients were treated by subtotal gastrectomy followed by irradiation of 4,000-4,500 cGy to the epigastric region and six courses of chemotherapy (vincristine, cyclophosphamide, prednisolone). In our review of the literature, 16 cases of gastric adenocarcinoma following the treatment of gastric lymphoma were found and listed with details. The factors influencing the development of this secondary carcinoma, mainly those treatment related are discussed. The possible role of both radiotherapy and chemotherapy in shortening the latent period for the development of stump carcinoma is emphasized.