Evaluation of predictor variables of diagnostic [18F] FDG-PET/CT in fever of unknown origin.

BACKGROUND: Fever of unknown origin (FUO) is defined as an illness having fever which lasts at least 3 weeks of duration and is higher than 38.3 ºC on several measurements. The causes are infections, malignancies, noninfectious inflammatory diseases and miscellaneous. If [18F]FDG-PET/CT helps the final diagnosis, it is called contributory. The aim of the study is to evaluate the predictor variables effecting a contributory PET/CT for the diagnosis. METHODS: This is a retrospective cohort study conducted between June 2006 and May 2015 including 76 patients. The evaluated predictor variables are age, sex, ESR, CRP, fibrinogen, ferritin, albumin, haemoglobin level, platelet count, total leukocyte count, neutrophil percentage, lymphocyte percentage, ALP, LDH, ALAT, ASAT, GGT, total bilirubin, CK, RF, ANA, urinanalysis, chest radiography, abdominal US, lymphadenopathy, duration of fever, comorbid diseases and previous therapies. RESULTS: ESR (P=0.001), CRP (P=0.001), fibrinogen (P=0.009), lymphopenia (P<0.001), neutrophilia (P<0.001), ferritin (P<0.001), leukocytosis (P=0.003), duration of fever before PET/CT (<3 months) were found to be statistically significant for positive contribution of PET/CT results to the diagnosis. CONCLUSIONS: [18F]FDG-PET/CT is helpful and contributory for the diagnosis of FUO in patients having higher levels of CRP, ESR, ferritin, fibrinogen, leukocytosis, neutrophilia and shorter durations of fever (<3 months).

A case of tension pneumothorax during hyperbaric oxygen therapy in an earthquake survivor with crush injury complicated by ARDS (adult respiratory distress syndrome).

Pneumothorax (PTX) is rarely reported in patients receiving hyperbaric oxygen (HBO2) therapy. Patients with air-trapping lesions in the lungs and those with a history of spontaneous PTX, lung disease, mechanical ventilation or chest trauma are at an increased risk for PTX during HBO2 therapy. A 28-year-old male earthquake survivor was referred to our center for multiple wounds 21 days after being rescued from the debris. He had been intubated and put on mechanical ventilation for three days because of adult respiratory distress syndrome (ARDS). At initial presentation, he was conscious, well-oriented and hemodynamically stable. The initial six HBO2 treatments were uneventful. On the seventh HBO2 treatment, the patient lost consciousness and developed cardiopulmonary arrest near the end of decompression. The HBO2 specialist accompanying the patient inside the chamber immediately initiated CPR. A diagnosis of tension PTX was made. After the patient was removed from the chamber, a chest tube was inserted, which improved the symptoms. Although rare, tension PTX can occur during HBO2 therapy. Early diagnosis and intervention are crucial for saving a patient's life. Increased vigilance is required during treatment of patients with risk factors for PTX.

Serum neuron-specific enolase and S-100ß levels as prognostic follow-up markers for oxygen administered carbon monoxide intoxication cases.

Serum neuron-specific enolase (NSE) and S-100ß levels are considered novel biochemical markers of neuronal cell injury. In this study, the initial and post-treatment levels of NSE and S-100ß were compared in carbon monoxide (CO) poisoning patients, who received normorbaric oxygen (NBO) or hyperbaric oxygen (HBO) therapy. Forty consecutive patients with acute CO poisoning were enrolled in this prospective, observational study. According to their clinical symptoms and observations, twenty patients were treated with NBO, and the other twenty with HBO. Serum S-100ß and NSE levels were measured both at time of admission and 6 h later (post-treatment). Serum NSE and S-100ß values decreased significantly in both of the therapeutic modalities. The initial and post-treatment values of NSE and S-100ß in NBO or HBO patients were comparable. A clear negative correlation was observed between the decrease of NSE and S-100ß levels and initial blood carboxyhemoglobin levels. In conclusion, the present results suggested the use of serum S-100ß and NSE levels as indicators for brain injury. Due to the significant increase of their values with oxygen therapy, they may also be useful as prognostic follow-up markers. However, the current findings reflected no difference between the efficacy of NBO or HBO therapy.

The effect of hyperbaric oxygen therapy on ischemia-modified albumin levels in people with diabetes with foot ulcers.

INTRODUCTION: Hyperbaric oxygen (HBO2) treatment accelerates the healing process of diabetic foot ulcers (DFU) by increasing tissue oxygenation in hypoxic tissues. Ischemia-modified albumin (IMA) is produced as a result of serum albumin flowing through ischemic tissues. We aimed to investigate the effect of HBO2 therapy on IMA levels in patients with DFU. METHODS: Thirty (22 male, eight female) patients with DFU were enrolled into this study. HBO2 therapy was performed five times a week. Blood samples were drawn before the first treatment, after the 10th (IMA10) and 20th (IMA20) hyperbaric sessions. RESULTS: Pretreatment IMA levels [median (25%-75% quartiles)] of the patients were 0.010 (0.002-0.150) absorbance units (ABSU). Compared to pretreatment values, IMA levels did not change significantly after the 10th session [0.006 (0.003-0.025) ABSU] and 20th session [0.009 (0.005-0.019) ABSU] (p = 0.527). We found statistically significant negative correlations between diabetic age and IMA10 (r = -0.448, p = 0.013) and IMA20 (r = -0.414, p = 0.023). CONCLUSION: In contrast to our expectations, IMA levels did not change with HBO2 therapy in patients with DFU. We think that IMA levels did not decrease due to the production of free oxygen radicals during HBO2 therapy. Further studies with larger groups may give more accurate results.

Predictive Value of Soluble CD14, Interleukin-6 and Procalcitonin For Lower Extremity Amputation in People with Diabetes with Foot Ulcers: A Pilot Study.

OBJECTIVE: The aim of this pilot study was to determine clinical and laboratory factors that predict amputation surgery and to evaluate the predictive value of soluble CD14 (sCD14), interleukin-6 (IL-6), and procalcitonin (PCT) in patients with diabetic foot ulcers (DFUs). METHODS: Twenty-seven (20 males, 7 females) Diabetic Foot Ulcers (DFU) patients admitted to our department were consecutively enrolled. The patients' demographics and wound characteristics were noted. IL-6, PCT, and sCD14 were measured at admission. RESULTS: Six of the 27 patients (22%) eventually underwent lower extremity amputation. Compared to the non-amputation group, a previous history of amputation (p=0.017), the presence of gangrene (p=0.044), the Wagner grade (p=0.011), the IL-6 concentration (p=0.018), the white blood cell count (WBC) (p=0.036), and the erythrocyte sedimentation rate (ESR) (p=0.042) were significantly high in the amputation group. However, the sCD14 and PCT concentration were not significantly different. CONCLUSION: We have shown for the first time that IL-6 may have predictive value for lower extremity amputation in patients with DFU. Further studies are needed to confirm its predictive value in this patient group.

Mean corpuscular volume is associated with endothelial dysfunction and predicts composite cardiovascular events in patients with chronic kidney disease.

AIM: Mean corpuscular volume (MCV) is a measure of size of red blood cells. Recently a few studies showed an association of macrocytosis with all-cause mortality. We aimed to assess the relationship of MCV with cardiovascular (CV) morbidity and mortality in patients with chronic kidney disease (CKD), and the effect of MCV on endothelial function. METHODS: This is an observational cohort study with a prospectively maintained cohort of patients with stage 1-5 CKD. Estimated glomerular filtration rate (eGFR), flow mediated dilatation (FMD) and laboratory values were measured at baseline. Multivariate linear and Cox regression analyses were used to predict independent associations of FMD and composite CV events, respectively. RESULTS: A total of 309 patients were included in the study. In contrast to anaemia MCV did not show a significant change among CKD groups. MCV was an independent predictor of FMD in addition to serum haemoglobin, CRP, diabetes, systolic blood pressure (SBP) and eGFR. Median MCV value was 85 fl. Kaplan-Meier analysis showed that at 38 months the survival rate was 97.6% in the group with MCV < 85 compared to 81.6% in the arm with MCV ≥ 85 (P < 0.001, log-rank test). Cox regression analysis showed MCV as a predictor of composite CV events independent of major confounding factors. CONCLUSION: This is the first study in the literature showing an independent association of MCV and FMD. Our results also determined MCV as an independent predictor of composite CV events independent of anaemia, inflammation, diabetes and eGFR in patients with CKD.

The relationship between microalbuminuria, left ventricular hypertrophy, retinopathy, and sex hormone status in newly diagnosed hypertensive women.

An increased incidence of hypertension (HT) in postmenopausal female population has been shown in previous studies and this has been ascribed to an association with altered status of estrogen (E2) and other female sex hormones. Hypertension is associated with certain target organ damage (TOD) and related clinical conditions. The aim of this study was to determine the relationship between microalbuminuria, left ventricular hypertrophy (LVH), retinopathy, and sex hormone status in newly diagnosed hypertensive women. A total of 66 hypertensive women (39 postmenopausal and 27 premenopausal) were included in the study. Along with the tests recommended in the HT guidelines, LVH, hypertensive retinopathy, and microalbuminuria were investigated in all the patients. Sex hormones (follicle stimulating hormone, luteinizing hormone, progesterone, and E2) of the patients were also measured. The results show that there was no statistically significant difference between the two groups in regard to TOD except microalbuminuria. The frequency of microalbuminuria in premenopausal group patients was higher than that of the postmenopausal group patients (P = .038). This study suggests that TOD caused by HT is a very important health problem, seeming to be related with female sex hormones.

The relationship between some of the cardiovascular risk factors and arterial stiffness parameters in essentially hypertensive patients.

Hypertensive patients have strong evidence of endothelial dysfunction. We aimed to explore the relationships between cardiovascular risk factors and arterial stiffness parameters in hypertensive patients. The study population included 109 hypertensive patients (63 females, 46 males). Arterial stiffness measures including pulse wave velocity, augmentation index, and central aortic pressure were applied. Augmentation index and central aortic pressure were found to be significantly higher (P < .001 and P = .03, respectively) in women. The higher augmentation index and central aortic pressure values were observed in women than in men. These data offer new evidences for the role of sex hormones in the pathogenesis of atherosclerosis in women.

Skinfold thickness as a predictor of arterial stiffness: obesity and fatness linked to higher stiffness measurements in hypertensive patients.

Hypertensive patients have strong evidence of endothelial dysfunction. Some novel endothelial dysfunction parameters such as pulse wave velocity (PWV), augmentation index (AIx), and central aortic pressure (CAP) have been investigated as predictive markers of atherosclerosis. It is well known that obesity has relationships with endothelial dysfunction and atherosclerosis. We aimed to investigate relationships between anthropometric measurements and arterial stiffness parameters in essentially hypertensive patients. The study population included 100 patients (56 females, 44 males) newly or formerly diagnosed as essentially hypertensive in an outpatient clinic. Arterial stiffness measurements, including PWV, AIx, CAP, and body mass index (BMI); waist circumference, hip circumference; waist/hip ratio; and triceps, biceps, subscapular, and suprailiac skinfold thicknesses were also applied to all the study patients. Then, the relationships between BMI, anthropometric measurements, and arterial stiffness parameters were investigated. The mean systolic arterial blood pressure of the study population was 135.85 ± 15.27 mm Hg and the mean diastolic arterial blood pressure of the study population was 84.17 ± 9.58 mm Hg. The parameters such as PWV, AIx, and CAP measured for arterial stiffness had correlations between BMI and different anthropometric measurements. The statistically significant correlations were present between PWV and triceps skinfold thickness (TST) (r = 0.377, P < .001) and it was also seen when regression analysis was performed (PWV = 6.41 + [0.072 × TST]; R(2) = 0.142, F[1-98] = 16.23, P < .001). Triceps skinfold thickness among these correlations may be used to estimate the carotid-femoral PWV, which is an indicator of subclinical organ damage due to hypertension.

Investigation of the aortic pulse wave velocity in patients with Gilbert's syndrome.

Arterial stiffness is currently the "gold standard" measure of aortic (carotid-femoral) pulse wave velocity (PWV), which is an important independent predictor of risk of developing a cardiovascular event. Gilbert's syndrome is a congenital disorder characterized by intermittent and non-hemolytic elevation of indirect bilirubin levels due to the deficiency of the enzyme UDP-glucuronyl transferase in the liver and many prospective studies found an inverse relationship between bilirubin levels and cardiovascular events in these patients. We aimed to investigate serum bilirubin levels and arterial stiffness parameters in patients with Gilbert's syndrome in this study. A total of 53 cases, consisting of 26 patients with a diagnosis of Gilbert's syndrome and 27 healthy control subjects, were included in the study. Serum bilirubin levels, other routine blood chemistry, and arterial stiffness measurements were recorded. The mean ages of Gilbert's syndrome and the control group were 31.5 ± 9.7 and 36.8 ± 11.1 years, respectively. PWV measurements were significantly lower in Gilbert syndrome patients (6.68 and 7.3 m/s in patients and controls; respectively) (P < .05). In correlation analysis in Gilbert's syndrome patients, PWV had a significant correlation with total and indirect bilirubin levels (r = -0.370, P = .009/r = -0.495, P = .003, respectively). Gilbert's syndrome patients have lower PWV measurements compared to healthy subjects, and the total and indirect bilirubin levels are also associated with PWV measurements. These findings may indicate the decreased atherosclerotic disease incidence in Gilbert's syndrome patients.

The comparative effects of valsartan and amlodipine on vWf levels and N/L ratio in patients with newly diagnosed hypertension.

High levels of circulating Von Willebrand factor (vWf) and increased neutrophil to lymphocyte (N/L) ratio may reflect vascular inflammation in hypertensive patients. In present study, we aimed to investigate the effects of valsartan as an angiotensin II receptor antagonist and amlodipine as a calcium channel blocker on the vWf levels and N/L ratio in patients with essential hypertension. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5-10 mg/day) as group A (n = 20 mean age = 51.85 ± 11.32 y) and angiotensine II receptor blocker (valsartan, 80-320 mg/day) as group B (n = 26 mean age = 49.12 ± 14.12 y). Endothelial dysfunction and vascular inflammation were evaluated with vWf levels and N/L ratio in hypertensive patients before treatment and after treatment in the 12th week. No statistically significant differences were found among the groups in terms of age, sex, and body mass index (BMI). There was a significant decrease in vWf levels (P < .001) and N/L ratio after treatment (P = .04, P < .001, respectively) in both the groups. Von Willebrand factor levels and N/L ratio are very important markers having a role in vascular inflammation and antihypertensive treatment with amlodipine and valsartan may improve cardiovascular outcomes by decreasing these biomarkers.

The comparative effects of valsartan and amlodipine on vascular microinflammation in newly diagnosed hypertensive patients.

Pentraxin 3 (PTX3) is a new candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors. We aimed to investigate the effects of valsartan and amlodipine on the PTX3 and C-reactive protein (CRP) levels in patients with essential hypertension. Patients with a newly diagnosed essential hypertension were admitted to our internal medicine outpatient clinic. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5-10 mg/day) as group A (n = 22; mean age ± standard deviation [SD]: 52 ± 11 year) and angiotensine II receptor blocker (valsartan, 80-320 mg/day) as group B (n = 28; mean age ± SD: 50 ± 14 year). Endothelial dysfunction and systemic inflammation were evaluated with PTX3 and CRP. There was a significant decrease in the level of PTX3 after treatment in two groups (P < .05). Although there was a significant decrease in the level of CRP after treatment in amlodipine group, there was no significant decrease in the levels of PTX3 and CRP after treatment in two groups. There were no significant differences in the systolic and diastolic blood pressure reduction between the two treatment groups. In the treatment of hypertension, prior knowledge of the level of plasma PTX3 could be important in antihypertensive drug choice. C-reactive protein and PTX3 are the markers that have role in vascular inflammation and are found associated with the prognosis of cardiovascular outcomes in many trials. In our study, PTX and CRP levels were decreased when compared to baseline levels.

An additional LDL-lowering effect of amlodipine; not only an antihypertensive?

Hypertension is a modifiable risk factor for cardiovascular diseases and is associated with several metabolic disorders like dyslipidemia. Higher levels of triglyceride and low-density lipoprotein (LDL) are quite strong factors for the development of cardiovascular diseases. In this study, we investigated the effects of valsartan and amlodipine on the lipid profile in patients with newly diagnosed essential hypertension. We observed a beneficial effect of amlodipine on the lipid profile with a significant reduction of LDL compared to valsartan. In the treatment of hypertension, prior knowledge of the plasma cholesterol levels can be important in antihypertensive drug choice.

Amlodipine increases vitamin D levels more than valsartan in newly diagnosed hypertensive patients: pointing to an additional effect on bone metabolism or a novel marker of inflammation?

Hypertension is a major challenge for public health. Appropriate antihypertensive treatment seem to provide a better life with lower morbidity and mortality rates. Another pathologic condition, osteoporosis, mainly affects postmenouposal women, and constitutes a growing body of risks after a particular age. As bone is a dynamic organ system that is directly related to calcium and phosphor metabolism, imbalance in these two parameters upon aging or menopause finally may lead to osteoporosis. Today, both osteoporosis and high blood pressure are major morbidities, especially in the elderly population. There are some intriguing results on the effects of antihypertensive agents on bone metabolism in the literature. In this study, we aimed to investigate the effects of widely used antihypertensive agents, valsartan and amlodipine on vitamin D levels in newly diagnosed hypertensive population. We found that amlodipine increased vitamin D levels significantly in patients with a newly diagnosed hypertension on a 12-week treatment duration compared to valsartan.

Findings of biopsy-proven chronicity and end-stage renal failure associated with oral sodium phosphate solution.

Bowel purgatives containing oral sodium phosphate (OSP) solution are used frequently in general practice and they have the potential of causing acute kidney injury especially in patients with some identified risk factors. Kidney injury may lead to chronicity and end-stage renal disease. Here we present, with renal biopsy findings, an elderly patient suffering from end-stage renal failure due to OSP solution.

Evaluation of the oxidative effect of long-term repetitive hyperbaric oxygen exposures on different brain regions of rats.

Hyperbaric oxygen (HBO(2)) exposure affects both oxidative and antioxidant systems. This effect is positively correlated with the exposure time and duration of the treatment. The present study aims enlightening the relation of HBO(2) with oxidative/antioxidant systems when administered in a prolonged and repetitive manner in brain tissues of rats. Sixty rats were divided into 6 study (n = 8 for each) and 1 control (n = 12) group. Rats in the study groups were daily exposed 90-min HBO(2) sessions at 2.8 ATA for 5, 10, 15, 20, 30 and 40 days. One day after the last session, animals were sacrificed; their whole brain tissue was harvested and dissected into three different regions as the outer grey matter (cortex), the inner white matter and cerebellum. Levels of lipid peroxidation and protein oxidation and activities of superoxide dismutase and glutathione peroxidase were measured in these tissues. Malondialdehyde, carbonylated protein and glutathione peroxidase levels were found to be insignificantly increased at different time-points in the cerebral cortex, inner white matter and cerebellum, respectively. These comparable results provide evidence for the safety of HBO treatments and/or successful adaptive mechanisms at least in the brain tissue of rats, even when administered for longer periods.

Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin- and trastuzumab-induced cardiotoxicity.

Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N-(3-(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague-Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as serum levels of creatine phosphokinase (CK-MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH-Px activities were significantly reduced in rats with DOX- or DOX+TRAST-induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK-MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX- and DOX+TRAST-treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.

Ozone therapy and hyperbaric oxygen treatment in lung injury in septic rats.

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1ß and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1ß, lung GSH-Px and histologic outcome.

The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy.

OBJECTIVES: Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. MATERIALS AND METHODS: Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). RESULTS: TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = -0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). CONCLUSION: TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.