ENDOTHELIAL DYSFUNCTION IN TRANSIENT ISCHEMIC ATTACK IN THE VERTEBRAL-BASILAR SYSTEM

2019 ◽  
pp. 17-24
Author(s):  
S. I. Henyk ◽  
V. A. Gryb ◽  
L. T. Maksymchuk ◽  
O. O. Doroshenko ◽  
Ya. I. Henyk
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Immunosorbent Assay ◽  
Transient Ischemic Attack ◽  
Stage I ◽  
Stage Iii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Circulatory Insufficiency ◽  
Significant Difference ◽  
Ischemic Attack

Transient ischemic attack (TIA) in the vertebral-basilar system (VBS) is characterized by an acute onset of focal neurological symptoms due to short-term local ischemia of the brain. According to various authors, temporary neurological manifestations of circulatory insufficiency in VBS can progress to complete stroke within 2-5 years in 30-50% of patients, leading to disability of about 80% of patients. Its diagnosis is associated with some difficulties due to the variability of clinical manifestations, clinical similarity with other diseases and, as a consequence, incorrect therapeutic tactics. The aim of the study was to investigate changes of endothelial function in TIA in VBS by determining the levels of homocysteine (HC) and vascular endothelial growth factor (WEGF) at different stages of neurological deficiency (ND). 78 patients with TIA in VBS were examined. The questionnaire developed by us was used to determine the stage of ND in TIA. The level of HC was determined by enzyme-linked immunosorbent assay. WEGF was determined using the "sandwich" method of enzyme-linked immunosorbent assay. In the group of patients with stage I ND, a tendency to HC increase in 1.1 times was detected compared with almost healthy persons (AHP), stage II - HC increased in 1.5 times (p <0.05), and stage III - in 1.9 times (p <0.05). Also significant difference (1.8 times) was revealed at stage III compared to the index of stage I (p <0.05). WEGF at the 1st stage of ND significantly increased in 1,7 times in comparison with AHP (p <0.05), at the 2nd stage there was a tendency to increase (in 1.2 times), at the 3d stage there was a significant increase in WEGF in comparison with AHP (in 2.9 times) (p <0.05), and compared with indicators of I (in 1.8 times) (p <0.05) and II stages (2.6 times) (p <0 , 05). We have shown that TIA in VBS is accompanied by endothelial dysfunction (increase in HC and WEGF), which is more pronounced with aggravation of the ND. To evaluate the prognosis of the disease, we recommend using a questionnaire for determination the stage of ND in TIA in VBS and to identify markers of endothelial function such as HC and WEGF.

ENDOTHELIAL DYSFUNCTION IN TRANSIENT ISCHEMIC ATTACK IN THE VERTEBRAL-BASILAR SYSTEM

2019 ◽  
pp. 17-24
Author(s):  
С. І. Геник ◽  
В. А. Гриб ◽  
Л. Т. Максимчук ◽  
О. О. Дорошенко ◽  
Я. І. Геник
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Immunosorbent Assay ◽  
Transient Ischemic Attack ◽  
Stage I ◽  
Stage Iii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Circulatory Insufficiency ◽  
Significant Difference ◽  
Ischemic Attack

Transient ischemic attack (TIA) in the vertebral-basilar system (VBS) is characterized by an acute onset of focal neurological symptoms due to short-term local ischemia of the brain. According to various authors, temporary neurological manifestations of circulatory insufficiency in VBS can progress to complete stroke within 2-5 years in 30-50% of patients, leading to disability of about 80% of patients. Its diagnosis is associated with some difficulties due to the variability of clinical manifestations, clinical similarity with other diseases and, as a consequence, incorrect therapeutic tactics. The aim of the study was to investigate changes of endothelial function in TIA in VBS by determining the levels of homocysteine (HC) and vascular endothelial growth factor (WEGF) at different stages of neurological deficiency (ND). 78 patients with TIA in VBS were examined. The questionnaire developed by us was used to determine the stage of ND in TIA. The level of HC was determined by enzyme-linked immunosorbent assay. WEGF was determined using the "sandwich" method of enzyme-linked immunosorbent assay. In the group of patients with stage I ND, a tendency to HC increase in 1.1 times was detected compared with almost healthy persons (AHP), stage II - HC increased in 1.5 times (p <0.05), and stage III - in 1.9 times (p <0.05). Also significant difference (1.8 times) was revealed at stage III compared to the index of stage I (p <0.05). WEGF at the 1st stage of ND significantly increased in 1,7 times in comparison with AHP (p <0.05), at the 2nd stage there was a tendency to increase (in 1.2 times), at the 3d stage there was a significant increase in WEGF in comparison with AHP (in 2.9 times) (p <0.05), and compared with indicators of I (in 1.8 times) (p <0.05) and II stages (2.6 times) (p <0 , 05). We have shown that TIA in VBS is accompanied by endothelial dysfunction (increase in HC and WEGF), which is more pronounced with aggravation of the ND. To evaluate the prognosis of the disease, we recommend using a questionnaire for determination the stage of ND in TIA in VBS and to identify markers of endothelial function such as HC and WEGF.

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P&lt;0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P&lt;0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

scholarly journals Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension

2021 ◽  
Vol 22 (1) ◽  
pp. 147032032199949
Author(s):  
Miaomiao Sang ◽  
Yu Fu ◽  
Chenmin Wei ◽  
Jing Yang ◽  
Xueting Qiu ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Primary Aldosteronism ◽  
Cardiovascular Events ◽  
Statistical Significance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microvascular Endothelial ◽  
Pai 1 ◽  
Microvascular Endothelial Function

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.

Abstract P426: Platelet Glycoprotein IIb/IIIa Inhibitors as an Adjunct to Stent Placement of Carotid Stenosis in Symptomatic Patients

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sachin M Bhagavan ◽  
Ammad Ishfaq ◽  
Muhammad F Ishfaq ◽  
Mukaish Kumar ◽  
Shruthi Pulimamidi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hospital Mortality ◽  
Carotid Stenosis ◽  
Transient Ischemic Attack ◽  
Stent Placement ◽  
Severe Disability ◽  
Platelet Glycoprotein ◽  
Carotid Stent ◽  
Significant Difference ◽  
Ischemic Attack

Background: Intra-arterial or intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors have been used as adjunct to stent placement of carotid stenosis in patients with ischemic stroke or transient ischemic attack. Objective: To determine the proportion of patients with ischemic stroke or transient ischemic attack who received platelet GP IIb/IIIa inhibitors as adjunct to carotid stent placement and associated outcomes. Methods: We analyzed data from Cerner Health Facts® which collected data from participating facilities from January 1, 2000 to July 1, 2018. We identified patients with ischemic stroke or transient ischemic attack who underwent carotid stent placement for carotid stenosis and received Abciximab, Eptifibatide, or Tirofiban. Outcome was defined by discharge destination and classified into none to minimal disability, moderate to severe disability, or death. Results: A total of 8.4 % of 4567 patients with ischemic stroke or transient ischemic attack who underwent carotid stent placement for carotid stenosis received platelet GP IIb/IIIa inhibitors. Patients who received platelet GP IIb/IIIa inhibitors were more likely to experience cerebral ischemia (14.8% versus 7.5%) and undergo intubation/mechanical ventilation (4.4% versus 2%). There was a significant difference between patients who did or did not receive platelet GP IIb/IIIa inhibitors in terms of in hospital mortality rates (2.7% versus 1.2%, p=0.0152), none to mild disability (67.3% vs 75.7%, p=0.0003), and moderate to severe disability (30.1% vs 23.1%,p=0.0024). Conclusions: Adjunct use of platelet GP IIb/IIIa inhibitors in patients undergoing carotid stent placement for symptomatic carotid stenosis was associated with increased rates of in hospital mortality and moderate to severe disability.

Small lymphocytic lymphoma.

1989 ◽  
Vol 7 (5) ◽  
pp. 598-606 ◽  
Author(s):  
W H Morrison ◽  
R T Hoppe ◽  
L M Weiss ◽  
V J Picozzi ◽  
S J Horning
Keyword(s):  
Clinical Course ◽  
Bone Marrow Involvement ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Stage I ◽  
Stage Iii ◽  
Small Lymphocytic Lymphoma ◽  
Significant Difference ◽  
Ann Arbor ◽  
Leukemic Phase

The clinical course of 54 patients with small lymphocytic lymphoma (SL) was reviewed. The majority of patients had disseminated lymphoma at the time of diagnosis; 14 patients (26%) presented with Ann Arbor stage I and II disease. Five- and 10-year survival for all patients was 76% and 49%. The only clinicopathologic features identified that predicted a shortened survival were the presence or absence of systemic (B) symptoms (15% v 63% at 10 years, P = .01) and a diffuse rather than pseudofollicular nodal architecture (47% v 87% at 10 years, P = .04). Initial bone marrow involvement was not an adverse prognostic factor for patients who presented with stage III and IV disease. Ten patients developed a marked lymphocytosis consistent with progression to a leukemic phase (chronic lymphocytic leukemia [CLL]). These ten patients had a median initial lymphocyte count of 2,790, compared with 1,580 for those patients who did not progress to CLL (P = .0001). Developing CLL did not adversely affect survival (P = .48). Thirty-seven patients were treated with various combinations of radiation and chemotherapy; 17 patients received no initial therapy. Ten-year freedom from relapse (FFR) for stage I and II patients treated with irradiation was 80% and 62%; FFR for stage III and IV treated patients was 11%. Despite the marked differences in FFR, no statistically significant difference in survival could be demonstrated between the various stages. Selected patients with advanced SL received no initial therapy; these patients had a 10-year survival that was not statistically different from the immediately treated stage III and IV patients. Patients with stage I and II SL should be treated with irradiation; prolonged FFR and possibly cure of the disease can be achieved in these patients.

Sleep-Related Leg Movements in Patients with Transient Ischemic Attack and Controls

2018 ◽  
Vol 79 (3-4) ◽  
pp. 171-176 ◽  
Author(s):  
Mirjam H. Schipper ◽  
Korné Jellema ◽  
Diego Alvarez-Estevez ◽  
Johan Verbraecken ◽  
Roselyne M. Rijsman
Keyword(s):  
Cardiovascular Diseases ◽  
Transient Ischemic Attack ◽  
Sleep Apnea Syndrome ◽  
Control Group ◽  
Periodic Leg Movements ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Significant Difference ◽  
Ischemic Attack ◽  
Leg Movements

Background: Periodic leg movements during sleep (PLMS) have been associated with an increased risk for cardiovascular diseases and there is a high prevalence of PLMS found in patients with obstructive sleep apnea syndrome (OSAS). We evaluated patients with transient ischemic attack (TIA) for PLMS and respiratory related leg movements (RRLM), versus a control group without TIA. Methods: Twenty-five patients with TIA and 34 patients with no vascular diagnosis were referred for polysomnography. Diagnosis of PLMS was made if the periodic leg movement index (PLMI) was ≥5 and clinical significant as PLMI ≥15. Results: There was no significant difference in PLMI ≥5 and ≥15 between patients with and without TIA. In the absence of OSAS, 2 out of 5 TIA patients (40%) had a PLMI ≥15 compared to 1 of the 19 patients without TIA (5%; p = 0.037). There was no increase in RRLMs when OSAS was present. Conclusions: TIA patients did not have higher PLMI compared to controls, and in the presence of OSAS, there was no increase in RRLMs compared to patients without TIA. In selective patients, PLMS could be associated with cardiovascular diseases, since PLMS was clinically more often found in the TIA group without OSAS.

Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

1988 ◽  
Vol 6 (11) ◽  
pp. 1722-1727 ◽  
Author(s):  
W J Curran ◽  
M J Kornstein ◽  
J J Brooks ◽  
A T Turrisi
Keyword(s):  
Relapse Rate ◽  
Salvage Therapy ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Subtotal Resection ◽  
Total Resection ◽  
Mediastinal Irradiation ◽  
Significant Difference

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

scholarly journals DIFFERENCES OF SALIVA LEPTIN LEVELS IN CHILDREN WITH CHRONIC KIDNEY DISEASE ON HEMODIALYSIS AND HEALTHY CHILDREN (STUDY IN CHILDREN WITH GINGIVITIS)

2018 ◽  
Vol 11 (4) ◽  
pp. 192
Author(s):  
Berthauli Esther Nurmaida ◽  
Heriandi Sutadi ◽  
Sarworini B Budiardjo ◽  
Eka Laksmi Hidayati
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Immunosorbent Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Significant Difference ◽  
The Difference

 Objectives: Analyze the difference of salivary leptin in between healthy children with gingivitis and hemodialysis (HD) children with gingivitis.Methods: A total of 20 children, ages 11–16-year-old with gingivitis, were chosen as subjects; 10 were on HD and 10 were healthy children. The level of salivary leptin was measured using the enzyme-linked immunosorbent assay method.Results: The results showed a significant difference of salivary leptin levels between the children on HD (61,300 ± 4151 pg/ml) and the healthy children (57,200 ± 3173 pg/ml).Conclusions: There is a significant difference in the salivary leptin levels in children on HD with gingivitis and healthy children with gingivitis.

scholarly journals Analysis of Radiation Therapy for the Control of Merkel Cell Carcinoma of the Head and Neck Based on 36 Cases and a Literature Review

2008 ◽  
Vol 87 (11) ◽  
pp. 634-643 ◽  
Author(s):  
Brian D. Lawenda ◽  
Michelle G. Arnold ◽  
Valerie A. Tokarz ◽  
Joshua R. Silverstein ◽  
Paul M. Busse ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Head And Neck ◽  
Local Control ◽  
Clinical Stage ◽  
Local Control Rate ◽  
Stage I ◽  
Stage Iii ◽  
Regional Control ◽  
Kaplan Meier ◽  
Significant Difference

Merkel cell carcinoma (MCC) is a rare and aggressive epidermal cancer. We conducted a retrospective study and literature review to investigate the impact that radiation therapy has on local, regional, and distant control as part of the oncologic management of MCC of the head and neck and to further elucidate the role of radiation therapy with regard to regional control for the clinically uninvolved neck. We reviewed all registered cases of head and neck MCC that had occurred at four institutions from January 1988 through December 2005. Treatment and outcomes data were collected on patients with American Joint Committee on Cancer stage I, II, and III tumors. Local, regional, and distant control rates were calculated by comparing variables with the Fisher exact test; Kaplan-Meier analysis was used to report actuarial control data. Stage I to III head and neck MCC was identified in 36 patients— 22 men and 14 women, aged 43 to 97 years (mean: 71.6) at diagnosis. Patients with stage I and II tumors were combined into one group, and their data were compared with those of patients with stage III tumors. Twenty-sixpatients(72%) had clinical stage I/II disease and 10 patients (28%) had clinical stage III disease. Median follow-up was 41 months for the stage I/II group and 19 months for the stage III group. Based on examination at final follow-up visits, local recurrence was seen in 7 of the 36 patients (19%), for a local control rate of 81 %. The 2-year actuarial local control rate for all stages of MCC was 83%; by treatment subgroup, the rates were 95% for those who had undergone radiation therapy to the primary site and 69%) for those who had not— a statistically significant difference(p = 0.020). Based on information obtained at final follow-ups, 10 of the 36 patients (28%) experienced a regional recurrence, for a regional control rate of 72%. The 2-year actuarial regional control rate among all patients was 70%; by subgroup, rates were 82%) for patients who had undergone regional node radiation therapy and 60% for those who had not— not a statistically significant difference (p = 0.225). Nine patients (25%) overall developed a distant metastasis, for a distant control rate of 75%. Salvage therapies included chemotherapy and/or radiation therapy to the metastatic site, but neither had any significant effect on survival. Regardless of treatment, the Kaplan-Meier survival curves leveled off at 30 months with 82% survival for the stage I/II group and at 19 months with 60% survival for the stage III group. We conclude that radiation therapy to the primary tumor site (either following resection or definitively) results in a local control rate of more than 90% in patients with head and neck MCC. We also found a trend toward improved regional control of the clinically negative neck with the addition of radiation therapy.

Serum Levels of OPG and MIP-1α in Untreated Multiple Myeloma Patients. Correlations with Staging, Survival and Bone Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5074-5074
Author(s):  
Argyro Papadogiannis ◽  
Marie-Cristine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Tatiana Tzenou ◽  
Antonios G. Antoniadis ◽  
...  
Keyword(s):  
Bone Disease ◽  
Staging System ◽  
Serum Levels ◽  
High Serum ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Bone Lesions ◽  
Disease Biology ◽  
Significant Difference

Abstract Cytokines, such as MIP-1a (macrophage inhibiting factor) and OPG (osteoprotegerin) are assumed to play a role in MM disease biology and bone disease, by mechanisms that are still under investigation. MIP-1a is constitutively secreted by myeloma cells, plays a possible role in the development of MM bone lesions, enhance MM cell adhesion to stromal cells and its serum levels have been recently related to survival in MM. OPG is a soluble decoy receptor which acts as a soluble receptor antagonist that prevents osteoclasts activation and the development of bone disease. Reported findings on serum OPG levels in MM patients are controversial as well as its possible role in the biology of the disease. In order to investigate the possible relationship of MIP-1a and OPG levels in MM patients with prognosis and bone disease, we determined by ELISA serum MIP-1a and OPG levels in 20 MGUS, 82 MM patients and 27 healthy individuals (HI). Both cytokines were determined by ELISA (R&D, Quantikine, USA) in frozen sera collected at dignosis, before treatment. The median age of MM patients was 69 years (44–84) and 50% were males. MM patients’ stage was as follows: 23 stage I, 28 stage II, 31 stage III according to Durie-Salmon staging system and 27 stage I, 17 stage II, 35 stage III according to the International Scoring System (ISS). In HI median MIP-1a was 28 pg/ml (15–54) and median OPG 1600 pg/ml (450–4600). In subjects with MGUS, median MIP-1a was 34 pg/ml (17–58) and median OPG 2300 pg/ml (820–6200). In MM patients, median pretreatment serum MIP-1a was 32 pg/ml (16–100) and OPG 3000 pg/ml (820–25000). No statistical significant difference was observed between HI, MGUS and MM patients with regard to MIP-1a levels but for OPG levels differences between HI and MM patients and between MGUS and MM patients were both significant (0.01 and 0.05 respectively). No relationship was found between MIP-1a or OPG levels and bone disease. However, there was a trend for longer survival in patients with MIP-1a or OPG levels lower than median (5-year overall survival 60 ± 12 vs 38 ± 14, p=0.08 and 66 ± 13 vs 29 ± 13, p=0.07 respectively). In addition MIP-1a levels were correlated with ISS stage: MIP-1a levels were 28.3±11.3 in ISS stage 1, 29.8±11.1 in ISS stage 2, 39±19.2 in ISS stage 3 (p=0.02). In conclusion, in our experience serum OPG levels are higher in MM patients than in MGUS or HI, MIP-1a levels are correlated with the ISS stage and both high serum MIP-1a and OPG levels at diagnosis are related with a shorter survival.

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