Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?

OBJECTIVE: Trace elements are essential for the biochemistry of the cell. Their reference values have been found to differ considerably in pregnant women stratified by age, place of residence, anthropometric status, and length of pregnancy. In optimal amounts, these elements reduce the risk of pregnancy complications. Subclinical hypothyroidism in pregnancy is associated with adverse maternal and neonatal outcomes. The aim of the study was to determine the effects of zinc (Zn), copper (Cu), magnesium (Mg), and rubidium (Rb) on pregnant women in an iodine deficiency region and find the relationship with the thyroid status and nutrition. METHODS: We evaluated the iodine status of 61 healthy pregnant women from an iodine deficient region in Bulgaria. Thyroid stimulating hormone (TSH) and thyroxin free (FT4) levels were measured using ELISA. RESULTS: We found elevated levels of copper that differed the most between the first and second trimesters; Cu and TSH were found to be positively correlated (р < 0.05). Lower Cu levels were found in pregnant women consuming pulses more than 2-3 times a week (р = 0.033). The women consuming fish more than 2-3 times a week had higher levels of Rb. We found a pronounced iodine deficiency in more than half of the examined women in the first to third trimesters, without any effect of pregnancy on the ioduria (р=0.834). All second and third trimester cases were associated with severe ioduria (< 150 µg/L). CONCLUSION: The high Cu levels were associated with subclinical hypothyroidism (SCH) and less pulse consumption during pregnancy in an iodine deficiency endemic area. SCH was found in 24% of the pregnant women in such an area while in 13% of them SCH had progressed to overt hypothyroidism.

Serum vitamin D levels and inflammatory status in COVID-19 patients.

OBJECTIVES: The coronavirus 2019 disease (COVID-19) is characterized by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of laboratory findings, depending on disease severity. BACKGROUND: We studied some laboratory parameters in correlation with vitamin D status representing the inflammatory state in hospitalized COVID-19 patients on admission. METHODS: The study included 100 COVID-19 patients with moderate (n=55) and severe (n=45) form of the disease. Complete blood count and differential blood count, routine biochemical parameters, C-reactive protein and serum procalcitonin, ferritin, human IL-6 and serum vitamin D (measured as 25-OH vitamin D) concentrations, were performed. RESULTS: According to the severity of the disease, patients with severe form had significantly lower serum vitamin D (16.54±6.51 ng/ml vs 20.37±5.63 ng/ml, p=0.0012), higher serum interleukin-6 (41.24±28.46 pg/ml vs. 24.75±16.28 pg/ml, p=0.0003), C-reactive protein (101.49± 57.15 mg/l vs 74.43±42.99 mg/l, p=0.0044), ferritin (969.89±338.37 ng/ml vs 845.96±359.91 ng/ml, p=0.0423) and LDH (1050.53±369.11 U/l vs 905.31±335.57 U/l, p=0.0222) compared to those with moderate form of the disease. CONCLUSION: The presented data provide a relationship between increased inflammatory laboratory markers, low vitamin D levels and disease severity in COVID-19 patients (Tab. 2, Fig. 3, Ref. 32).

Markers of activation of coagulation in cancer patients.

BACKGROUND: Prothrombotic tendency is characteristic of tumors. The aim of the study is to investigate the changes in the laboratory parameters for coagulation and fibrinolysis, namely in fibrinogen, thrombin-antithrombin complex (ТАТ), tissue factor (ТF), prothrombin fragment (F1+2), antithrombin III (AT III), D-dimer and screening coagulation tests in cancer patients before initiation of chemotherapy. MATERIALS AND METHODS: Levels of F1+2, fibrinogen, ТАТ, AT III, TF, D-dimer, PT, aPTT and TT were measured baseline in 80 patients with breast and lung cancer before systemic treatment. The same parameters were investigated in 65 healthy volunteers. TF, ТАТ, F1+2 were measured by ELISA; AT III, D-dimer, fibrinogen and screening coagulation tests were measured by automated coagulation system Sysmex CS 2000i.  RESULTS: Levels of F1+2, fibrinogen, ТАТ, TF, and D-dimer in cancer patients were significantly higher than those in the control group, while the levels of ATIII activity were significantly lower (p < 0.001). The highest area under the ROC curve was for D-dimer, which made it a good marker for the risk of thrombosis. CONCLUSION: Higher levels of TF, ТАТ, F1+2, fibrinogen and D-dimer and lower activity of АТ III in cancer patients support our hypothesis of an association between malignant disease and coagulation disorders. Cancer patients are at an increased risk of thrombosis wherefore antithrombotic prophylaxis may be considered (Tab. 6, Fig. 2, Ref. 34). Text in PDF www.elis.sk Keywords: coagulation, fibrinolysis, cancer.

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.

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.

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-hour 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.

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.

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.

Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis.

YKL-40, also known as human cartilage glycoprotein 39, is a member of the "mammalian chitinase-like proteins" family without chitinase activity. Increased serum concentrations are associated with inflammatory processes and several types of cancer. In this study, we evaluated YKL-40 levels in serum and synovial fluid of patients with rheumatoid arthritis in comparison with the ultrasonographic findings. YKL-40 levels were measured by enzyme-linked immunosorbent assay in 25 patients with active rheumatoid arthritis and in 40 healthy subjects. B mode and power Doppler were performed to determine synovial thickening and vascularization. Serum YKL-40 level in patients was significantly higher than the concentration in healthy controls (P < 0.01). In patients with rheumatoid arthritis, the level of the glycoprotein in synovial fluid was remarkably elevated compared to the serum level (P = 0.003). The B mode and power Doppler scores correlated to YKL-40 in serum and synovial fluid (P = 0.07). Serum YKL-40 levels were related positively to serum markers of inflammation such as C-reactive protein (P = 0.004) and erythrocyte sedimentation rate (P = 0.003). This study is the first to demonstrate a relationship between YKL-40 levels and ultrasonographic examinations in Bulgarian patients with rheumatoid arthritis. The findings suggest that YKL-40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation.

Assessment of clinical utility and predictive potential of pre-chemotherapy soluble urokinase plasminogen activator receptor: Observational single center study.

Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a prerequisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and therelevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3 - 5.11). In univariate Cox regression, suPAR was predictive of shortened progression-free survival (PFS) (hazard ratio 1.065, 95% confidence interval 1.002 - 1.13; p = 0.041). There was a trend towards shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state.

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.

Salivary mental stress biomarkers in COVID-19 patients.

Background: During the COVID-19 pandemic, mental health disorders and level of stress show a major increase compared to before the pandemic. Coronavirus-related stress is recently the leading cause of negative impacts on global mental health. Thus, maintaining positive mental health is as important as maintaining physical health during COVID-19. The aim of this study was to analyze salivary mental stress biomarkers as cortisol, alpha-amylase, and chromogranin A in hospitalized patients with COVID-19 to compare their potential relationship with stress symptoms. Material and methods: A total of 80 adult hospitalized patients with moderate COVID-19 disease and a control group (n = 80) randomly selected were conducted as participants. Saliva cortisol (sCort), saliva alpha-amylase (sAA), and saliva and chromogranin A (sCgA) were determined by the ELISA method (Bio Vendor, USA). Symptoms of stress were measured with a stress symptom checklist (SSCL). Results: The patients group presented significantly higher levels of sCort, sAA, and sCgA compared with the control group. The correlation analysis showed a positive correlation with strong strength between sCort and sAA (r = 0.934, p < 0.01), as well as sAA with sCgA (r = 0.714, p < 0.01). A moderate positive correlation was found between sCort with sCgA (r = 0.618, p < 0.05). Based on their stress scores from the SSCL the patients were associated with high stress level (30.00%) and very high stress levels (67.5%). In terms of the controls, all the participants showed a low to moderate stress level. We found significant positive correlation between levels of stress and salivary biomarkers. Conclusion: Data from our study demonstrated that salivary biomarkers are promising tools of exploring COVID-19 related stress.

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.

Longitudinal Dynamics of Coagulation and Angiogenesis Markers in Cancer Patients During and After Chemotherapy.

Hemostatic parameters have been investigated as molecular determinants of tumor progression. To analyze the dynamics of microparticle-associated tissue factor activity (MPTF), tissue factor antigen (TF-Ag), and angiopоietin-2 (ANG-2) in cancer patients before, during, and after active treatment and to explore their potential as biomarkers for metastatic occurrence and death. Blood for the analysis of MPTF, TF-Ag, ANG-2, and conventional hemostatic tests was sampled in 111 patients with various cancers at 4 consecutive visits: before first chemotherapy cycle, after 3 courses, at the sixth course, and 3 months after chemotherapy cessation. Patients were followed up until metastatic progression/death or the end of the study. MPTF did not change during chemotherapy, but increased significantly after treatment cessation. Total TF-Ag and ANG-2 decreased throughout active treatment. Significant drop of their levels was observed 3 months post therapy cessation. Progressive disease was significantly associated with higher pre-chemotherapy TF-Ag and fibrinogen. Elevated baseline levels of fibrinogen were associated with increased risk of shortened progression free survival. Cessation of chemotherapy is associated with significant change of hemostatic parameters. Pre-chemotherapy levels of TF-Ag and fibrinogen may be informative of disease state and prognosis.

Associations of serum sclerostin with bone mineral density, markers of bone metabolism and thalassaemia characteristics in adult patients with transfusion-dependent beta-thalassaemia.

Aim of the study: To assess serum sclerostin in transfusion-dependent beta-thalassaemia patients versus healthy controls and to examine its associations with bone mineral density, bone metabolism markers and beta thalassaemia alterations.Material and methods: Sixty-two transfusion-dependent beta-thalassaemia (TDßT) patients and 30 healthy controls were evaluated for serum sclerostin, osteocalcin, beta-cross laps, osteoprotegerin and serum level of receptor activator of nuclear factor kappa-Β ligand (sRANKL). Bone mineral density was measured at the lumbar spine and femoral neck. Thalassaemia characteristics were collected from the patients' medical records.Results: A significantly higher sclerostin level (median 565.50 pmol/L) was observed in the transfusion-dependent beta-thalassaemia patients vs. the healthy controls (median 48.65 pmol/L, p < .001). Sclerostin showed significant associations with the Z-scores at the lumbar spine and femoral neck, osteocalcin, beta-cross laps, osteoprotegerin, sRANKL, pretransfusion haemoglobin, liver iron concentration and female gonadal state. Significantly higher levels of sclerostin were observed in splenectomized TDßT patients and in those with fragility fractures. Age, sex, body mass index, disease severity, serum ferritin, cardiac T2* and male gonadal state did not show significant associations with sclerostin.Conclusion: Sclerostin may play a role in the bone pathophysiology of beta-thalassaemia patients and could serve as a marker of severe osteoporosis.KEY MЕSSAGESSerum sclerostin is more than 10-fold higher in adult patients with transfusion-dependent beta-thalassaemia compared to healthy controls.Serum sclerostin is negatively associated with bone mineral density and the bone synthesis markers and positively with the bone resorption indices.Serum sclerostin is significantly associated with pre-transfusion haemoglobin, liver iron concentration, splenectomy status and fragility fracture events in adult patients with transfusion-dependent beta-thalassaemia.Serum sclerostin could serve as a marker of severe osteoporosis in beta-thalassaemia patients.

Multiple Myeloma with Advanced Bone Disease and Low Tumor Burden - Different Clinical Presentation but Similar Outcome after Bortezomib-Based Therapy and Radiotherapy.

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.