Adenosine receptor A2a blockade by caffeine increases IFN-gamma production in Th1 cells from patients with rheumatoid arthritis.

OBJECTIVE: Studies indicate that caffeine uptake may be a risk factor for rheumatoid arthritis (RA), but a definitive link between caffeine consumption and RA has not been established. This study aimed to investigate the interplay between caffeine, adenosine receptor A2a, and interferon-γ (IFN-γ) production in CD4+ T cells from RA patients. METHOD: Peripheral blood mononuclear cells were obtained from the peripheral blood of healthy individuals and patients with RA. CD4+ T cells were isolated using the magnetic activated cell sorting technique and cultured in vitro with caffeine or mock control. In addition, adenosine was used as a competitive inhibitor of caffeine. After 48 h, expression of IFN-γ and interleukin-17 (IL-17) was analysed by flow cytometry. Ex vivo expression levels of adenosine receptor A2a were also assessed. RESULTS: Caffeine promoted IFN-γ production in Th1 cells in vitro. Significantly higher concentrations of caffeine were required to increase IFN-γ levels in Th1 cells from healthy individuals compared to Th1 cells from patients with RA. Moreover, ex vivo levels of adenosine receptor A2a expression on CD4+ T cells were significantly higher in RA than in healthy individuals. Caffeine-driven IFN-γ production was completely reversed by adenosine, a competitive agonist of adenosine receptor A2a. In contrast to IFN-γ, production of IL-17 was not affected by caffeine. CONCLUSION: Caffeine promotes IFN-γ production in Th1 cells from RA patients in vitro by competitive inhibition of adenosine receptor A2a. Excessive coffee consumption could contribute to T-cell activation and inflammation in RA.

Plasma E-selectin levels can play a role in the development of diabetic retinopathy.

PURPOSE: Diabetic retinopathy is one of the leading causes of blindness. There are several risk factors, such as the duration of diabetes or glycemic control of the patient; however, several biochemical factors also alter the process. Our aim was to investigate the role of soluble E-selectin in the formation of diabetic retinopathy. PATIENTS AND METHODS: Fifty-seven patients (37 female and 20 male, aged 61.71 ± 12.31 years) and 14 healthy control subjects (ten female and four male, aged 63.06 ± 10.46 years) were enrolled in the study. We measured the soluble E-selectin level in the plasma of patients by ELISA. All patients underwent careful ophthalmological examination, including ophthalmoscopy and color fundus photography, while diabetic retinopathy grading was performed in line with the 2012 classification of the American Academy of Ophthalmology (AAO). RESULTS: The soluble E-selectin level was significantly higher in patients with diabetes compared to controls (32.95 ng/ml vs. 26.55 ng/ml, p = 0.03). Dividing patients into groups by the presence of retinopathy, the E-selectin level was also significantly higher in the retinopathy group (p < 0.05). When we examined diabetic patients by the severity of retinopathy (groups A, B, and C, by the guidelines of the AAO), however, we did not find any significant difference in soluble E-selectin levels, although it tended to be higher in group B. CONCLUSIONS: An elevated E-selectin level can play a role in the development of diabetic retinopathy, but it does not seem to alter disease severity. However, glycemic control and the reduction of cardiovascular risk factors may also alter the level of E-selectin that might play a role in the prevention of diabetic retinopathy.

BODY MASS INDEX AS A PROGNOSTIC FACTOR FOR DISEASE PROGRESSION IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH BEVACIZUMAB BASED SYSTEMIC THERAPY.

CONTEXT: Epidemiological data have shown that obesity increases the risk of developing colorectal cancer and also an increased body mass index (BMI) is associated with a worse prognosis. Bevacizumab based systemic therapy, an antiVEGF targeted therapy, is an important treatment option for metastatic colorectal cancer (mCRC) patients. Obesity is associated with high level of vascular endothelial growth factor (VEGF), that might provoke resistance to antiVEGF monoclonal antibody. OBJECTIVE: To evaluate the efficacy in terms of progression free survival (PFS) and overall survival (OS) of bevacizumab systemic therapy in patients with mCRC. DESIGN: Retrospective cohort, single center study. SUBJECTS AND METHODS: Between January 2007 and December 2012, 112 patients with mCRC, who followed bevacizumab based systemic therapy in the "Ion Chiricuta" Oncology Institute in Cluj-Napoca, were included in our analysis. RESULTS: Values of BMI ≥ or <27 kg/sqm was found that PFS is statistically significant superior in patients with BMI<27 kg/sqm (n=77) than in those with BMI ≥ 27 kg/sqm (n=35), 24 months versus 17.9 months (p = 0.04). Five years OS was not influenced by the BMI, 35% vs 30% (p=0.29). In patients with liver metastases with values of BMI ≥ 27 kg/sqm have PFS lower than patients with a BMI <27 kg/sqm, 17.5 months versus 24.5 months (p = 0.02). Five years OS was not influenced by the BMI, 39% (BMI <27 kg/sqm) vs. 22% (BMI ≥ 27 kg/sqm) (p = 0.09). CONCLUSIONS: This study demonstrated the negative influence of BMI on both PFS on the entire sample of patients and in patients with liver metastases only, BMI cut-off value proved to be 27 kg/square meter and shows that the BMI may be an important prognostic factor with a high clinical relevance in patients with mCRC.

A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv.

Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the targeting domain in a CAR, while antibodies in the natural format are often available. To overcome the limitation, we designed a CAR that uses an antibody in its natural configuration for binding. Such CAR consists of two chains, the immunoglobulin light and heavy chain with their constant regions, whereby the heavy chain is anchored to the membrane and linked to an intracellular signalling domain for T-cell activation. The two chains form a stable heterodimer, a so-called dual chain CAR (dcCAR), and bind with high affinity and in a specific manner to their cognate antigen. By specific binding, the dcCAR activates engineered T cells for the release of pro-inflammatory cytokines and for target cell lysis. We provide evidence by three examples that the dcCAR format is universally applicable and thereby broadens the CAR cell therapy towards a larger variety of targets for which an scFv antibody is not available.

[Differential diagnosis of Graves' orbitopathy. Case report]. / Az endokrin orbitopathia differenciáldiagnosztikája.

Graves' orbitopathy is the extrathyroidal manifestation of Graves' disease, which is the most common cause of exophthalmos. As eye symptoms usually coincide with the development of thyrotoxicosis, the diagnosis of the disease is rarely difficult. The aim of the authors was to summarize the differential diagnosis of Graves' orbitopathy based on literature review and presentation of their own four problematic cases on this topic. They conclude that symptoms similar to endocrine orbitopathy are present in other disorders. Endocrinologists need to be aware of these other conditions to avoid treatment failures.

Vascular endothelial growth factor levels in tears of patients with retinal vein occlusion.

PURPOSE: We measured vascular endothelial growth factor (VEGF) levels in tear fluid and serum in patients with retinal vein occlusion (RVO). PATIENTS AND METHODS: Eight patients with RVO due to secondary macular oedema were examined. VEGF levels were measured by enzyme-linked immunosorbent assay. All patients had a full ophthalmic examination (visual acuity, slit lamp biomicroscopy, perimetry, and fluorescein angiography). Central retinal thickness (CRT) was examined using optical coherence tomography (OCT). Tear and serum samples were collected and examinations were performed at diagnosis and 1 and 4 weeks later. RESULTS: VEGF levels in the tears of RVO eyes were significantly higher than in fellow eyes at diagnosis and after both 1 and 4 weeks (paired t test, p1 = 0.01, p2 = 0.02, p3 = 0.006). We found a weak but significant positive correlation between VEGF levels in tear fluid and serum of patients with RVO (r = 0.21), while this correlation tended to be stronger between the fellow eyes and serum levels (r = 0.33). CONCLUSION: To the best of our knowledge, we are the first to report an increased level of VEGF in the tear fluid of patients with RVO. Alterations of VEGF levels in tears may be useful for determining stages of RVO. This non-invasive and objective method may also be helpful for estimating the severity of macular oedema and efficacy of treatment.

The investigation of GSTP1, APC and RASSF1 gene promoter hypermethylation in urine DNA of prostate-diseased patients.

OBJECTIVES: Prostate cancer (PCa) represents one of the most complicated human tumors and, like many others malignancies, arises from progressive genetic and epigenetic alterations. Among all recognized epigenetic alterations, aberrant DNA methylation (hypo- and hypermethylation) is the most important and the best characterized change in PCa. BACKGROUND: We analyzed GSTP1, APC and RASSF1 gene promoter hypermethylation in urine DNA of ten previously non-treated prostate-diseased patients. METHODS: For the purpose, the quantitative real-time methylation specific PCR (MSP) with primers designed for amplification of methylated bisulfite-converted human DNA, followed by melting procedure, was currently optimized. RESULTS: GSTP1 gene promoter hypermethylation was detected in 2 and 1 out of 5 patients with biopsy-confirmed PCa using the primers covering the 3´ and 5´ CpG regions of the promoter, respectively. The APC gene promoter hypermethylation was found in neither of PCa or non-PCa patients and the RASSFI gene promoter hypermethylation was found in some non-PCa and not in all PCa patients. CONCLUSIONS: Our results suggest that GSTP1 gene promoter hypermethylation can be detected in urine DNA of PCa patients with real-time MSP followed by melting. This enables evaluation of its potential as a useful biomarker in the diagnosis and prognosis of PCa (Tab. 1, Fig. 1, Ref. 9).

Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer.

BACKGROUND AND PURPOSE: This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. MATERIALS AND METHODS: Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. RESULTS: The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. CONCLUSION: The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases.

Brain metastasis from non-small cell lung cancer (NSCLC): prognostic importance of the number of involved extracranial organs.

BACKGROUND AND PURPOSE: This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 × 4 Gy or 10 × 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung + bone vs. lung+lymph nodes vs. other combinations) extracranial organs. RESULTS: The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥ 4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥ 70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. CONCLUSION: The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement.

[Novel treatment opportunities in Graves' orbitopathy]. / Új lehetoségek az endokrin orbitopathia kezelésében.

Graves' orbitopathy is the most common extrathyroidal manifestation of Graves' disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves' orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves' orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted.

A new survival score for patients with brain metastases from non-small cell lung cancer.

BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) is the most common primary tumor in patients developing brain metastasis. This study was performed to develop and validate a survival score particularly for this group of patients. PATIENTS AND METHODS: In this study, the data of 514 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastasis from NSCLC were retrospectively analyzed. The patients were divided into a test group (n = 257) and a validation group (n = 257). In the multivariate analysis of the test group, gender, performance status, and extracranial metastases were independent predictors of survival and, therefore, included in the scoring system. The score for each of the three factors was obtained from the 6-month survival rate (in %) divided by 10. The total scores that represented the sum of the three scores were 5, 8, 9, 11, 12, or 15 points. Three prognostic groups were formed according to the total scores. RESULTS: The 6-month survival rates in the test group were 9 % for 5-9 points (group A), 54 % for 11-12 points (group B), and 79 % for 15 points (group C). In the validation group the 6-month survival rates were 14, 56, and 78 %, respectively. The comparisons between the prognostic groups A, B, and C of the test and the validation group did not reveal any significant differences. CONCLUSION: This new score appears valid and reproducible. It can help predict the survival of patients with brain metastasis from NSCLC.

A simple survival score for patients with brain metastases from breast cancer.

BACKGROUND AND PURPOSE: Personalized cancer treatment considers the patient's survival prognosis. Therefore, it is important to be able to estimate the patient's survival time, particularly in a palliative situation such as brain metastasis. This study aimed to create and validate a survival score for patients with brain metastasis from breast cancer, which is the second most common primary tumor in these patients. PATIENTS AND METHODS: Data of 230 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastasis from breast cancer were retrospectively analyzed. Patients were assigned to a test (n = 115) or a validation group (n = 115). According to the results of the multivariate analysis of the test group, Karnofsky Performance Score and extracranial metastases were included in the scoring system. The score for each factor was obtained from the 6-month survival rate (in %) divided by 10. Total scores represented the sum of these scores and were 4, 7, 9, or 12 points. Three prognostic groups were formed. RESULTS: The 6-month survival rates in the test group were 10 % for 4-7 points, 55 % for 9 points, and 78 % for 15 points (p < 0.001). In the validation group the corresponding 6-month survival rates were 11, 54, and 75 %, respectively (p < 0.001). The comparisons between the prognostic groups of the test and the validation group did not show significant differences. CONCLUSION: This simple survival score appears valid and reproducible. It can be used to estimate the survival time of patients with brain metastasis from breast cancer receiving WBRT alone.

Brain metastasis. Prognostic value of the number of involved extracranial organs.

BACKGROUND AND PURPOSE: This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis. MATERIAL AND METHODS: The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs. RESULTS: The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 51, 30, 16, 13, and 10%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95% confidence interval 1.18-1.34; p<0.001). According to the multivariate analysis, age (p<0.001), gender (p=0.002), and KPS (p<0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved. CONCLUSION: The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis.

Complete scrotal urinary bladder hernia with both ureters and small intestine presenting as dysuria, bilateral ureterohydronephrosis, and acute renal insufficiency.

We report a case of a complete scrotal bladder hernia with both ureters presenting as dysuria, bilateral ureterohydronephrosis, and acute renal insufficiency. A 37-year-old man with a recurrent large scrotal mass after two surgeries, suffering with small urinary symptoms as a dysuria and nocturia, was examined before the third surgery on an outpatient basis. Urological examination revealed a negative urine, bilateral large ureterohydronephrosis on USG, and serum creatinine 231-250 µmol/l. CT displayed the urinary bladder completely herniated into the scrotum with distal parts of both ureters and small intestine, and bilateral large ureterohydronephrosis. After admission to urological department on retrograde cystography a completely herniation of the urinary bladder with residual urine more than 250 ml was confirmed. A permanent catheter was indwelled. The hernia was explored with urinary bladder repositioning. Because bilateral ureteral obstruction on USG did not retreat, a bilateral percutaneous nephrostomy was done. The patient's serum creatinine markedly improved, also hernia and ureterohydronephrosis was repaired with normally moisten without residual urine (Fig. 2, Ref. 26).

Primary obstructed megaureter (POM) in children.

UNLABELLED: The aim of this study was to analyze the results of surgical and conservative treatment of non-refluxing POM. In the period 2000-2009, 45 children (52 ureters) were treated, the average age was 5.8 months (±10.33), 24 children (26 ureters) by surgery (I) and 21 children (26 ureters) by conservative means (II). The average follow-up period was 73.8 (±32.91) and 30.85 months (±23.1) resp. Urine examination, USG, DTPA99mTc, biochemical testing, micturating cystouretography in all patients were performed. Significant difference was present in the occurrence of hydronephrosis of 0th, 3rd and 4th grade, p10 mm, p<0.01; and in the occurrence of normal and prolonged time T ½, p<0.01. The health condition was adjusted in 13 (54.20 %), improved on DTPA99mTc in 5 (20.85 %), non-improved in 3 (12.50 %), deteriorated in 1 (4.15 %) and unknown in 2 (8.3 %) patients. In the IInd group a significant difference was in case of occurrence of hydronephrosis of 0th, 2nd and 3rd grade, (p<0.01, or p=0.037 and p=0.011) and in occurrence of normal ureter, with ureter 0-5 mm and dilated ureter 5-10 mm, p<0.01. The condition at the end of the follow-up period was assessed DTPA99mTc as adjusted in 11 (52.39 %) patients, improved in 6 (28.57 %), unimproved in 3 (14.28 %) and no patient was assessed as having deteriorated and unknown in 1 (4.76 %). CONCLUSION: In patients with an impaired separate kidney function, early surgical treatment helps to minimize damage to the kidney function and prevents future complications (Tab. 6, Fig. 3, Ref. 32).

The recurrent primary retroperitoneal liposarcoma.

AIM: Describe a patient with multiple recurrences of the primary recurrent liposarcoma. CLINICAL CASE: A 60-years-old man complained of weight loss (BMI 18.4) with a palpable huge retroperitoneal tumour, which displaced left kidney, and was confirmed on USG and CT. Laboratory examination showed anaemia and pathological blood tests. Chest X-ray initially showed a negative finding. A complete transperitonealy surgical extirpation of the tumour with left side nephrectomy was performed on June 28, 2007. The tumour mass weight was 1900 g. It was lying on the posterior face of the kidney in diameters 170x120x120 mm, completely capsulated by thin grey-pink capsula with peripheral fat tissue on the section grey-pink, lobulary shaped, in ¾ parts with central necrotic changes. Histopathologically was confirmed the primary dedifferentiated (non-lipogenous) liposarcoma low grade of malignancy. Nephrectomy specimen was confirmed as age related finding. There was no evidence of positives surgical margins. Despite oncological and surgical treatment, followed repeated recurrence with eight transperitoneal surgeries in the retroperitoneum and abdomen with extirpation of the metastases, left side hemicolectomy, splenectomy and repeated extirpation tumour metastases from abdomen and radix mesenterii. Last tumour weighed 2900 grams. Patient died on January 9, 2011, after the eight surgeries on multiorgans failure due to hemorrhagic shock and persistent atrial fibrilaton by cardiopulmonary insufficiency. As a speciality, he was treated without transfusion because as Jehovah´s witness he refused blood derivates. CONCLUSION: Despite complex surgical and oncological treatment, the prognosis in patient with recurrent liposarcoma was fatal (Tab. 1, Fig. 5, Ref. 50).

What is the significance of a microscopically positive resection margin in the curative-intent treatment of rectal adenocarcinoma? A retrospective study.

PURPOSE: The aim of this study was to analyze the characteristics of patients with rectal cancer operated with a microscopic positive margin (R1) and thus avoid these situations or adapt treatment in these particular cases. METHODS: We reviewed all the pathology data of resected specimens from patients with rectal or recto-sigmoid cancer operated with curative intent at the Institute of Oncology "Prof. Dr. Ion Chiricuta" between 2000-2011 (763 patients in 12 years) and the pathology files of patients from other institutions referred for adjuvant treatment to our hospital (318 patients). We included patients with anterior resection, Hartmann's procedure and abdomino-perineal resection, but we excluded patients with local excision and patients with R2/R1 at first, but R0 after re-resection (56 patients). We have identified 31 patients with R1, but had to exclude one case from analysis because this patient was lost to follow-up. RESULTS: With surgery alone the local relapse (LR) was unavoidable. In the neoadjuvant chemoradiation (CRT) group 85.7% of the patients did not develop LR despite of R1. In the adjuvant CRT cohort 50% of the patients were LR-free at 2 years after conventional radiotherapy (p<0.01). CONCLUSION: Based on these results it is concluded that a clear resection margin is extremely important for the local control of rectal cancer, because it cannot be always compensated by adjuvant CRT. In R1 cases neoadjuvant CRT seems to offer better prognosis than adjuvant CRT. To avoid R1 and its consequences a good quality control of total mesorectal excision (TME) is needed and CRT should be done before and not after surgery. R1 after primary surgery needs to be compensated by re-resection if possible, otherwise probably high dose radiotherapy with chemotherapy is needed.

[Unfavourable cardiovascular consequences of adult growth hormone deficiency]. / A felnottkori növekedésihormon-hiány szív- és érrendszeri szövodményei.

The growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis plays a crucial role in maintaining the normal function of the cardiovascular system. Results of the last decades demonstrated that GH-IGF-1 takes part in regulating peripheral resistance and contributes to preserving physiological cardiac mass and left ventricular function. Vasculoprotective functions of the GH-IGF-1 axis are believed to counteract atherosclerosis. Unlike in childhood, when GH-deficiency results in growth retardation, GH deficiency does not cause specific symptoms in adults. Adult growth hormone deficiency (AGHD) is characterized by a clustering of cardiometabolic risk factors resulting in a clinical picture similar to the metabolic syndrome. Besides visceral obesity, dyslipidemia and insulin resistance, novel cardiovascular risk factors, such as chronic low-grade inflammation, oxidative stress and prothrombotic state have also been reported in AGHD and may contribute to the increased cardiometabolic risk. Based on a growing body of evidence, long-term GH-replacement improves lipid profile significantly and has a favorable impact on body composition, endothelial function, left ventricular mass as well as the novel, non-traditional cardiometabolic risk factors. Increased mortality associated with the disease is now considered to be multicausal and as such cannot be solely attributed to the GH-deficiency. The etiology of GH-deficiency, treatment of the underlying pathology as well as the inadequate treatment of coexisting hormonal deficiencies might also be responsible for the increased mortality. Nevertheless, in hypopituitarism, adequate replacement therapy including GH-substitution may result in a mortality that is comparable to the general population. Orv Hetil. 2023; 164(41): 1616-1627.

Microsomal epoxide hydrolase polymorphisms, cigarette smoking and prostate cancer risk in the Slovak population.

Polymorphisms in tobacco carcinogen metabolizing enzymes may generate interindividual variations towards the risk of developing prostate cancer. One of these enzymes is microsomal epoxide hydrolase (EPHX1) which metabolizes polycyclic aromatic hydrocarbons, or PAH, carcinogens found in cigarette smoke. The activity of this enzyme is affected by two polymorphisms, a substitution of Tyr113 by His in exon 3 and a substitution of His139 by Arg in exon 4. The aim of this study was to use a population-based case-control study to investigate whether or not such genetic polymorphisms in EPHX1 gene can modify the relationship between smoking status and the risk of developing prostate cancer. We used restriction fragment length polymorphism, or PCR-RFLP to determine EPHX1 genotypes in subjects comprising 194 patients with histologically verified prostate cancer and 305 healthy individuals as control. We found no overall association between prostate cancer risk and functional polymorphisms of EPHX1 gene in exon 3 and exon 4. We further analysed the association between the EPHX1 genotypes and smoking. Smokers carrying the exon 3 Tyr/Tyr and Tyr/His genotypes were at no significant risk compared to non-smokers with the "rapid" Tyr/Tyr genotype. By contrast, a significant interaction of smoking and the exon 4 polymorphism was present.

[Is there a relationship between inflammatory markers, oxidative stress and postoperative atrial fibrillation?]. / Existuje vztah medzi zápalovými markermi, oxidacným stresom a pooperacnou fibriláciou predsiení?

INTRODUCTION: Atrial fibrillation (AF) is one of the most common complications following heart surgery. The aim of this work was to verify the relationship between inflammatory markers, oxidative stress and postoperative arrhythmia. METHODS: 45 patients with ischemic heart disease (12 women and 33 men, mean age 62.3 ± 9.4 years) underwent surgical myocardial revascularization. The extracorporeal circulation (ECC) was used in 30 patients, without ECC was 15 patients. During the first 3 postoperative days was determining the incidence and duration of the AF, laboratory markers of inflammation (CRP, leukocytes, TNFα), malondialdehyde (MDA). RESULTS: Demographic data and associated disease were in this patients similar. The incidence of AF we documented in 30 patients (66.7%). In patients with postoperative AF were significantly higher levels of inflammatory markers (leukocytes 13.6 ± 3.6 vs 11.3 ± 3.6; 14.7 ± 3.9 vs 12.5 ± 2.9; 13.7 ± 4.1 vs 11.4 ± 13.7; p 0.05; CRP 138.1 ± 41.1 vs 69.9 ± 25.8; p 0.001; TNFα 11.3 ± 14.3 vs 8.7 ± 3.6; 12.1 ± 14.5 vs 8.7 ± 3.1; p 0.05) compared with patients who were free from AF. Values of MDA were not significantly different. CONCLUSION: Patients with post-operative atrial fibrillation were higher levels of inflammatory markers compared with patients with sinus rhythm but no significant differences in the levels of oxidative stress.