Multipli mijelom s uznapredovalom koštanom bolešću i niskim tumorskim opterećenjem – različite kliničke manifestacije ali sličan ishod nakon terapije na osnovi bortezomiba i radioterapije

There is a small but well recognized group of patients with multiple myeloma (MM), characterized by multiple bone lesions and low tumor burden, the so-called macrofocal form of MM (MF-MM). The aim of the study was to analyze the incidence, clinical manifestation, therapeutic outcome and prognosis of patients with MF-MM treated with bortezomib-based therapy and radiotherapy, in comparison to classic MM. There were 148 MM patients treated with bortezomibbased regimens, with 15 (10.1%) of them meeting the criteria for MF-MM. Comparative analysis involved disease- and therapy-related variables and markers of bone metabolism in MF-MM and classic MM groups. Event-free survival (EFS) and median survival (MS) were analyzed. Patients in MF-MM and classic MM groups had similar mean age and sex distribution. Patients with MF-MM had advanced myeloma bone disease (MBD), significantly lower clonal plasma cell infiltration in bone marrow, and lower paraprotein level. These patients were predominantly in an early International Staging System stage, showed non-secretory and light-chain variants, and significant association with extramedullary plasmacytomas. EFS was 20 months in MF-MM group versus 13 months in classic MM group (nonsignificant difference). MS was 42 months in both MF-MM and classic MM groups. MF-MM presents with imbalance of the minimal tumor burden and massive bone involvement. Along with advanced skeletal manifestations, these patients showed features of preserved bone marrow and no end-organ damages. Following bortezomib-based therapy and radiotherapy, the EFS and MS did not differ between MF-MM and classic MM groups.Postoji manja, ali dobro prepoznata skupina bolesnika s multiplim mijelomom (MM) koja je obilježena višestrukim oštećenjima kostiju i niskim tumorskim opterećenjem, tzv. makrofokalni oblik MM (MF-MM). Cilj ovoga istraživanja bio je analizirati incidenciju, kliničke manifestacije, ishod terapije i prognozu u bolesnika s MF-MM liječenih terapijom na osnovi bortezomiba i radioterapijom u usporedbi s klasičnim MM. Ukupno je 148 bolesnika s MM liječeno terapijom na osnovi bortezomiba, od kojih je 15 (10,1%) ispunjavalo kriterije za MF-MM. Usporedbena analiza obuhvatila je varijable povezane s bolešću i terapijom te biljege koštanog metabolizma u skupinama bolesnika s MF-MM i klasičnim MM. Analizirano je preživljenje bez ispada (event-free survival, EFS) te medijan preživljenja (median survival, MS). Distribucija prema srednjoj dobi i spolu bila je slična u skupinama s MF-MM i klasičnim MM. Bolesnici s MF-MM imali su uznapredovalu mijelomsku bolest kostiju, značajno niži stupanj infiltracije klonskih plazma stanica u koštanoj srži te nižu razinu paraproteina. Ovi bolesnici bili su pretežito u ranom stadiju prema Međunarodnom sustavu stadija bolesti, imali su ne-sekrecijske i lako-lančane varijante te značajnu pridruženost ekstramedularnih plazmacitoma. EFS je bio 20 mjeseci u skupini s MF-MM prema 13 mjeseci u skupini s klasičnim MM (neznačajna razlika). MS je bio 42 mjeseca u objema skupinama bolesnika. MF-MM se manifestirao kao neravnoteža minimalnog tumorskog opterećenja i velikim zahvaćanjem kostiju. Uz uznapredovale skeletne manifestacije, ovi bolesnici su imali očuvanu koštanu srž i izostanak oštećenja krajnjih organa. Nakon terapije zasnovane na bortezomibu i radioterapije nije bilo razlike u EFS i MS između skupina bolesnika s MF-MM i klasičnim MM

Changes in intima media thickness, ankle brachial index and flow mediated dilation in pre hypertensive individuals

Introduction: Prehypertension (PH) is a state being on the frontier between the physiological referent arterial pressure values and pathological ones. The opinion concerned with its treatment is contradictory. Vascular alteration is an object of interest.Material and methods:  Intima Media Thickness (IMT), Ankle Brachial Index (ABI) and Flow Mediated Dilation (FMD) indices were examined in 103 individuals with PH and 45 normotensives. Anthropometric and clinical chemical methods were also applied. The statistical processing was carried out by ÐœS Excel 2000 and SPSS 11.0.Results: The pre hypertensives` metabolic profile was unfavorable, they are overweight and have bigger waist size, reflecting in higher cardiovascular risk. The percentage of FMD is reduced as an expression of endothelial function. Structural vascular alterations are not registered - ITM and ABI values are of no significant difference in the two followed up groups.Conclusion: The therapeutic approach in prehypertensives should be directed to reestablishment of the endothelial function.

Evaluation of Anxiety, Depression, and Biological Markers in Health Professionals with Burnout 

Introduction: Medical profession is a stress factor for the development of burnout, symptoms of anxiety and depression as a result of 24-hour work, delayed work-life balance gratification and challenges associated with patient care. Aim: This study aimed to verify the rates of burnout, anxiety, and depression presented by health professionals working 24-hour shifts under emergency conditions. Saliva cortisol and glycated hemoglobin were also studied as stress-related biomarkers. Materials and methods: Ninety-five medical professionals – physicians, biologists, chemists, and laboratory technicians were compared to a control group working outside medicine. Burnout was measured by the Maslach Burnout Inventory. Anxiety and depression were measured by the State-Trait Anxiety Inventory and the Zung Depression Scale. Salivary cortisol and glycated hemoglobin were analyzed by the immunoassay methods. Results: The level of burnout in the subscale of emotional exhaustion was high in 95.6% of medical professionals. In the subscale of personal accomplishment, 100% had high scores. Regarding the State-Trait Anxiety Inventory, 22.2% and 68.9% of the medical specialists showed a positive score (≥40) for S-anxiety and T-anxiety scale, respectively. 11.1% indicated greater anxiety (score ≥ 55) for T-anxiety. In relation to the depression scale, 31.1% had mildly depressive states and 8.9% had moderately depressive states. Participants with a high level of emotional exhaustion presented higher results for saliva cortisol and glycated hemoglobin compared to the control group. A significant positive correlation existed between the two dimensions - emotional exhaustion and depression (r=0.683, p<0.01).Conclusions: Our study may be relevant for further research in order to decrease the negative aspects of professional stress

Burnout Syndrome in Physicians—Psychological Assessment and Biomarker Research

Background and objectives: Burnout is a syndrome typically occurring in work environments with continuous and chronic stress. Physicians are at increased risk for burnout, as a result of 24-h work, delayed work−life balance gratification, and the challenges associated with patient care. The aim of the present study was to evaluate the psychological parameters of burnout symptoms in relation to biomarkers of stress among physicians with different medical specialties. Materials and methods: A total of 303 physicians were contacted as potential participants. A comparison group of 111 individuals working outside medicine was used as a control to verify the results. The physicians were specialists in internal medicine, general surgery, pathology, and primary care. Serum cortisol, salivary cortisol, adrenocorticotropic hormone (ACTH), insulin (IRI), and prolactin levels were analyzed by chemiluminescence enzyme immunoassay (Access 2, Beckman Coulter). Fasting glucose in serum and glycated hemoglobin (HbA1C) in whole blood were measured using the automatic analyzer AU 480 Beckman Coulter system. Symptoms of burnout were measured with the Maslach Burnout Inventory (MBI). Results: The group with burnout presented significantly higher levels of serum and saliva cortisol, ACTH, prolactin, fasting glucose, and HbA1C compared with the control group. The correlation analysis between biomarkers showed a positive correlation with moderate strength between serum and saliva cortisol (r = 0.516, p = 0.01),as well as serum and saliva cortisol with ACTH (r = 0.418; r = 0.412, p = 0.01) and HbA1C (r = 0.382; r = 0.395, p = 0.01). A weak positive correlation was found between serum and saliva cortisol with prolactin (r = 0.236; r = 0.267, p < 0.01) and glucose (r = 0.271; r = 0.297, p < 0.01). In the multiple logistic regression model, saliva cortisol, HbA1C, and age were significantly associated with burnout (chi-square = 16.848, p < 0.032). Conclusion: Our findings demonstrated the interest of exploring biomarkers of stress related to burnout in health professionals

The role of fibrinogen in acute ischaemic stroke

Aim. This study aimed to explore associations between fibrinogen and acute ischaemic stroke, neurological impairment, cerebral ischaemia, and clinical evaluation of stroke patients.Materials and methods. The study involved 153 patients categorised into two groups: patients with acute ischaemic stroke, and patients with risk factors but who had not had a stroke. Blood samples were collected to analyse the serum level of fibrinogen. The time from stroke onset to blood test was noted. The National Institutes of Health Stroke Scale was used to determine the neurological disability of the stroke patients upon hospital admission and upon discharge. Cerebral CT was performed on the same group of patients during the first 24 h after stroke onset and evidence of early ischaemic lesions was recorded. The stroke cases were divided into subgroups according to the TOAST classification.Results. Patients with ischaemic stroke had a significantly increased mean level of fibrinogen (> 4g/l). Analysis of stroke subtypes shows that patients with undetermined cause of stroke and patients with atherosclerotic stroke had a significantly higher median level of fibrinogen compared to patients with some other types of stroke. No significant connection was found between fibrinogen level and neurological deficit. A positive linear relationship was established between fibrinogen and blood sample time. A negative relation was established between the clinical evolution of ischaemic stroke patients and fibrinogen level. A significant relation between fibrinogen level and the presence of ischaemic lesions on cerebral CT was observed: patients with a fibrinogen level > 3.41g/l showed a 3.29-times increased risk of ischaemic lesions.Conclusion. Fibrinogen is a reliable biomarker that could characterise acute ischaemic stroke

YKL-40 IN SERA OF BREAST TUMOR PATIENTS

YKL-40, also known as human cartilage glycoprotein 39, is a member of the “mammalian chitinase-like proteins”, but lacking of chitinase activity. Increased variations in serum concentrations are associated with inflammatory processes and several types of cancer.In this study we evaluated serum YKL-40 levels in healthy controls and in women with benign and malignant breast tumors. YKL-40 serum levels were measured by enzyme-linked immunosorbent assay – ELISA in 32 patients. The effect of the various factors was analyzed using correlation and regression analyses simultaneously determining the size and direction of correlation. The level of statistical significance of null hypothesis was P<0.05. Our study showed that serum YKL-40 level in breast carcinoma was significantly higher than the concentration in healthy controls (p<0.01). The changes in protein levels were higher than 25%. Serum YKL-40 increased with age (rxy=0.46). The correlation between glycoprotein quantity and age was positive, but feeble.This investigation is first in Bulgaria to demonstrate significantly elevated serum YKL-40 level in breast carcinoma compared to women with benign breast tumors and healthy controls. Longitudinal studies are needed to confirm YKL-40 as a potential and reliable biomarker

A single-center study of bone mineral density in adult patients with severe hemophilia A in correlation with markers of bone metabolism

Introduction: Osteopenia and osteoporosis are well-known hemophilia A comorbidities. The pathogenesis of bone turnover alteration resulting in reduced bone mass includes impaired osteoblastic differentiation and disinhibition of RANKL-induced osteoclastogenesis as a result of a low FVIII level. Aim: To evaluate the bone mineral density (BMD) in adult patients with severe hemophilia A and assess a possible correlation with the bone remodeling biomarkers OPG/RANKL, CTX-1, osteocalcin, and Vit D. Materials and methods: 28 male subjects with severe hemophilia A and 33 age-matched controls were recruited. The biomarkers were tested with the ELISA assay and BMD with DEXA of the lumbar spine (LS) and total hip (TH). Results: The patients had lower LS-BMD (−0.955±0.145 vs. 1.118±0.079, p=0.05) and TH-BMD (−0.840±0.147 vs. 0.951±0.075, p=0.05) than those of the controls. The TH T-scores were −1.41±0.91 vs. 0.4±0.49 (p=0.05) and the LS T-scores −1.16±1.046 vs. 0.14±0.72 (p=0.05). 66.6% of patients under 50 years had osteopenia and 8.3% had osteoporosis. Fifty percent of those over 50 years old had osteopenia and 20% had osteoporosis. We found significantly higher OPG levels (123.69±107.05 vs. 41.98±18.95, p=0.05) than that in controls and lower sRANKL levels (23.49±29.39 vs. 131.32±201.27, p=0.05) and sRANKL/OPG ratio (0.27±0.35 vs. 5.28±10.01, p=0.05) than those in controls. A positive correlation was found between sRANKL and the BMD T-score of lumbar spine (p=0.001) in the patient group. Conclusions: sRANKL level and ratio can be used as predictors of low BMD

Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis

Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease

Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent

Background and objectives: The clinical use of non-steroidal anti-inflammatory drugs is limited due to high incidence of adverse drug reactions. The pyrrole heterocycle is included in the chemical structure of a number of drugs with various activities and shows relatively good tolerability and safety. The objectives of our study were to evaluate the analgesic and anti-inflammatory activity, as well as possible organ toxicity, of 2-[3-acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid (compound 3g), a novel N-pyrrolylcarboxylic acid structurally similar to celecoxib. Materials and methods: All experiments were performed on 6-week-old male Wistar rats divided into parallel groups (n = 8). Antinociception was assessed using animal pain models with thermal and chemical stimuli (paw withdrawal, tail-flick, and formalin tests). Criteria for the analgesic effect were increased latency in the paw withdrawal and tail-flick tests and decreased paw licking time in the formalin test compared to animals treated with saline (control). Anti-inflammatory activity was measured using a carrageenan-induced paw edema model; the criterion for anti-inflammatory effect was decreased edema compared to control. Blood samples were obtained after animals were sacrificed to assess possible organ toxicity. Statistical analysis was performed with IBM SPSS 20.0. Results: 2-[3-Acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid had analgesic action against chemical stimulus after single and multiple administration and against thermal stimulus after single administration. Compound 3g significantly suppressed carrageenan-induced paw edema after both single and continuous administration. After continuous administration, hematological tests showed that compound 3g decreased leukocyte and platelet levels and elevated serum creatinine levels. Conclusions: Antinociception with the tested compound is most likely mediated by spinal, peripheral, and anti-inflammatory mechanisms. Possible tolerance of the analgesic action at the spinal level develops after continuous administration. Anti-inflammatory activity is significant and probably the leading cause of antinociception. After multiple administration, compound 3g showed signs of potential nephrotoxicity and antiplatelet activity, as well as suppression of leukocyte levels

Use of saliva stress biomarkers to estimate novice male endoscopist’s stress during training in a high-end simulator

Objective: Simulated endoscopic training can be challenging and stressful for the novice trainee. The absence of a reliable stress detection method during simulated endoscopic training makes estimating trainees’ mental stress difficult to quantify. This study concomitantly measures the responses of four saliva stress biomarkers and compares them to the video score (VS) achieved by novice endoscopists in a reproducibly stressful simulation environment. Methods: Thirty-six male endoscopy naïve surgery residents were enrolled. After an orientation phase, a saliva specimen was collected for cortisol (sC), alpha-amylase (sAA), Chromogranin A (sCgA), and immunoglobulin A (sIgA) measurements (baseline phase, BL). Thereafter, the simulation exercise phase (E) started, practicing in the Fundamentals of Endoscopic Surgery Skills module (GI-Bronch Mentor). Immediately after, a second saliva sample for measuring the above-cited biomarkers was collected. The whole experiment was videotaped, and the VS was calculated. The percentage (E-BL)diff of each of the four saliva biomarkers was calculated and examined for correlation to VS. Results: sCgAdiff showed the best correlation with VS, followed by sAAdiff. Conclusions: sCgA and sAA, are saliva stress biomarkers that are easy to collect non-invasively and showed the best correlation with novice endoscopist’s performance in our simulation setting, and therefore, they could be used for monitoring stress