Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis.

OBJECTIVES: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV). METHODS: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described. RESULTS: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity. CONCLUSIONS: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.

Interleukin-6 and soluble interleukin-6 receptor are elevated in large-vessel vasculitis: a cross-sectional and longitudinal study.

OBJECTIVES: To investigate serum levels of IL- 6 and soluble IL-6 receptor (sIL-6R) in patients with large-vessel vasculitis and their relationship with disease activity. METHODS: Sera were obtained from 33 Takayasu's arteritis (TAK) patients and 14 giant cell arteritis (GCA) patients, and from 60 age-matched normal controls (NCs). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Among TAK patients with active disease at baseline, clinical records and serum samples from 11 TAK patients were available for the longitudinal study. IL-6 and sIL-6R serum levels were evaluated using commercial ELISA kits. RESULTS: IL-6 and sIL-6R serum levels were significantly higher in both GCA and TAK patients compared to NCs. IL-6 levels in TAK patients were significantly increased irrespective of disease phase, while a significant increase in sIL-6R concentrations was only found in TAK patients with active disease. Conversely, in GCA, IL-6 levels were significantly raised only in patients with active diseases, whereas sIL-6R levels appeared to be significantly higher irrespective of disease activity. Longitudinal analysis showed that levels of sIL-6R in TAK patients were significantly higher only at baseline, compared to NCs, whereas IL-6 levels were found to be significantly increased at each follow-up time point. CONCLUSIONS: These overall results might suggest a role for sIL-6R as a potential biomarker for disease activity in TAK patients, whereas in GCA, modifications of IL-6 might better identify patients with active disease.

The usefulness of volume NT software in measuring the fetal nasal bone at 11 to 13 + 6 weeks of gestation.

OBJECTIVE: The objective of this study is to investigate the reproducibility of 3D ultrasound to measure the fetal nasal bone (NB) at first trimester. METHODS: A group of singleton viable pregnancies attending the 11 to 13 + 6 weeks aneuploidy screening at the University of Bologna were prospectively selected. For each patient, fetal NB was measured by 2D ultrasound. Subsequently, a 3D ultrasound of the fetal head was acquired, and fetal NB was measured by offline analysis using the volume nuchal translucency software. The correlation between 2D and 3D ultrasounds and the reproducibility of fetal NB measurement at 3D ultrasound were assessed. RESULTS: Overall, 161 Caucasian women were included in the study. At 3D ultrasound, NB measurement showed an excellent intraobserver [Oper 1, intraclass correlation coefficient (ICC) = 0.98; Oper 2, ICC = 0.921] and interobserver agreement (rc = 0.92). The agreement between 2D and 3D measurements was moderate (rc = 0.77). CONCLUSIONS: A 3D ultrasound supported by the volume nuchal translucency software may provide reliable measurements of the fetal NB in the first trimester.

Ultrasonographic predictors for the development of joint damage in rheumatoid arthritis patients: a single joint prospective study.

OBJECTIVES: This paper aims to evaluate if any ultrasonographic aspect of metacarpo-phalangeal (MCP) joint can be predictors for the development of new joint damage, at single joint level, in rheumatoid arthritis (RA) patients. METHODS: Two hundred and forty MCP joints of 24 patients with RA were prospectively evaluated both clinically and by ultrasound (US) at time 0, at six months and 12 months, in order to collect the following variables: presence of synovial hypertrophy and power-Doppler (PD) vascularisation both graded on a semiquantitative (0-3) scale, and the number and dimension of bone erosions. X-ray examinations were carried out at time 0 and at 12 months and lesions were graded using the Sharp/van der Heijde (S/vdH) method at single joint level. Potential prognostic determinants for joint damage obtained at the first examination and during follow-up were entered in a conditional logistic regression analysis. RESULTS: Fifteen out of seventeen (88%) of the new eroded joints on x-rays examination had persistent PD vascularity and 14/17 (82%) had persistent synovial thickening (p=0.001 and p=0.02, vs. non-eroded joints, respectively). In multiple conditional logistic regression analysis, the most important factor associated with the development of radiological joint damage was the presence of a synovial PD score ≥2 on two or more US evaluations (OR 8.51 [95%CI 1.84-39.48] for Rx new erosions and OR 8.30 [95%CI 1.97-38.9] for increased S/vdH local joint score). Both baseline synovial score ≥2 and presence of Rx erosions were also significantly associated with the development of radiological joint damage. Two predictive models for x-ray erosions and total single joint level S/vdH damage score were constructed consisting of 2 baseline plus one longitudinal variable with a ROC AUC of 0.916 (95%CI 0.867-0.965) and 0.886 (95%CI 0.814-0.957). CONCLUSIONS: At the single joint level, the presence of US determined synovial thickness and PD signal at baseline and the persistent PD signal over time have relevant prognostic value for the development of articular damage in the same MCP joints of RA patients.

The Minimal Clinically Important Difference Changes Greatly Based on the Different Calculation Methods.

BACKGROUND: The minimal clinically important difference (MCID) for patient-reported outcome measures (PROMs) expresses both the extent of the improvement and the value that patients place on it. MCID use is becoming increasingly widespread to understand the clinical efficacy of a given treatment, define guidelines for clinical practice, and properly interpret trial results. However, there is still large heterogeneity in the different calculation methods. PURPOSE: To calculate and compare the MCID threshold values of a PROM by applying various methods and analyzing their effect on the study results interpretation. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3. METHODS: The data set used to investigate the different MCID calculation approaches was based on a database of 312 patients affected by knee osteoarthritis and treated with intra-articular platelet-rich plasma. MCID values were calculated on the International Knee Documentation Committee (IKDC) subjective score at 6 months using 2 approaches: 9 methodologies referred to an anchor-based approach and 8 methodologies to a distribution-based approach. The obtained threshold values were applied to the same series of patients to understand the effect of using different MCID methods in evaluating patient response to treatment. RESULTS: The different methods employed led to MCID values ranging from 1.8 to 25.9 points. The anchor-based methods ranged from 6.3 to 25.9, while the distribution-based ones were from 1.8 to 13.8 points, showing a 4.1× variation of the MCID values within the anchor-based methods and a 7.6× variation within the distribution-based methods. The percentage of patients who reached the MCID for the IKDC subjective score changed based on the specific calculation method used. Among the anchor-based methods, this value varied from 24.0% to 66.0%, while among the distribution-based methods, the percentage of patients reaching the MCID varied from 44.6% to 75.9%. CONCLUSION: This study proved that different MCID calculation methods lead to highly heterogeneous values, which significantly affect the percentage of patients achieving the MCID in a given population. The wide-ranging thresholds obtained with the different methodologies make it difficult to evaluate the real effectiveness of a given treatment questioning the usefulness of MCID, as currently available, in the clinical research.

Living with rotationplasty--quality of life in rotationplasty patients from childhood to adulthood.

BACKGROUND: Knowledge about the long-term sequelae of rotationplasty, in adults treated surgically in childhood for Osteosarcoma in the lower limb, mainly concerns function and performance; the aim of this study is to explore the experience and the Quality of Life (QoL) of the patients who underwent Rotationplasty from 1986 to 2006 in Italy. METHODS: Quantitative test: Administration SF-36 questionnaire to 20 subjects aged ≥16 years. Qualitative test: Semi-structured interview recorded in 10 of these subjects. RESULTS: Greater well-being was found in the Mental Component Summary (MCS) scale of subjects aged over 24 years, with a score mean of 54.2 (±4.8), compared with that of those aged up to 24 years, with a mean score of 48.0 (±6.6), P = 0.04. Relational and emotional difficulty in adolescence, which had been partially overcome in adulthood, was revealed. CONCLUSIONS: The assessment of QoL by the SF-36 questionnaire was effective, and a correspondence was found between what emerged from the quantitative study and the contents of the interview. Knowing the strengths and weaknesses that were highlighted is indispensable for parents and operators when choosing among the various surgical options and to facilitate coming to terms with the injury and the "scars".

Effect of ascorbic acid-rich diet on in vivo-induced oxidative stress.

Using hyperbaric oxygen (HBO) therapy as an in vivo oxidation model, we investigated the effect of a diet enriched in ascorbic acid (AA) on HBO-induced oxidative stress. Volunteers (n 46) were allocated to the AA-rich diet group or the control group. Blood samples were collected at the basal time, after the 1-week diet before and immediately after the HBO treatment, and 1 week after the HBO treatment. AA level, total antioxidant status (TAS), hydroperoxides (HP), lymphocyte DNA oxidation and DNA repair capacity were assessed. The expression of genes involved in oxidative stress was evaluated in lymphocytes and the protein activity of the modulated genes was determined in the plasma. The AA level and the antioxidant status of plasma were increased by AA-rich food consumption. HBO exposure did not affect the AA levels or TAS, but induced HP formation in the control group. The lymphocytes isolated from dietary-supplemented subjects were resistant to ex vivo DNA oxidation, showing an increased DNA repair capacity compared with controls. A difference in gene expression pattern was observed between the groups. AA-rich foods provide dual protection against oxidative stress, enhancing plasma antioxidant levels and stimulating genes involved in cell detoxification.

[Effectiveness of the transparent sterile dressing vs standard to fix the peripheral venous catheter (PVC) on the incidence of phlebitis. A randomized controlled trial]. / Efficacia della medicazione sterile trasparente rispetto a quella standard per il fissaggio del catetere venoso periferico (CVP) sull'incidenza delle flebiti.Trial randomizzato e controllato.

UNLABELLED: Effectiveness of the transparent sterile dressing vs standard to fix the peripheral venous catheter (PVC), on the incidence of phlebitis. A randomized controlled trial. INTRODUCTION: The type of dressing could contribute to the incidence of phlebitis, infiltration and accidental removals but the results of the studies are contrasting and samples are limited. AIM: To compare the effectiveness of a transparent polyurethane sterile dressing on the rate of phlebitis associated to peripheral venous catheter (PVC) vs a non sterile sticking plaster in use in current practice (standard dressing). DESIGN: Randomized controlled trial. Participants. 1061 PVCs (703 patients, adults and children) at a research orthopedic hospital in the north of Italy; 540 PVCs allocated to receive the sterile and 521 the standard dressing. RESULTS: 96 PVCs were excluded for phlebitis, 48 (9.6%) in the sterile and 48 (10.1%) in the standard dressing group, RR 0.96 (95%CI 0.697 - 1.335). Accidental removal of the PVCs was more frequent with the sterile dressing (9.6% vs 6.3%) but the number of catheters removed without complications was larger in the standard dressing group (48.9% vs 54.9% P=0.0503). Eighty-five PVCs were replaced for detachment of the dressing (50, 9.2% sterile and 35, 6.7% standard dressing). The cheapest transparent sterile dressing costs 32 cents while the standard 9 cents. CONCLUSIONS: A sticking non sterile plasters is not influential on the rate of phlebitis and ensures an good fix of the PVC compared the transparent sterile dressing to of polyurethane film.

Use of polyurethane foam inside plaster casts to prevent the onset of heel sores in the population at risk. A controlled clinical study.

AIM: The aim of this study was to test the effectiveness of polyurethane foam in contact with the heel inside a plaster cast to decrease the rate of pressure sores in the population at most risk. BACKGROUND: The rate of pressure sores caused by the plaster cast is reported to be 14-15% in the paediatric population, 33.3% in patients having undergone chemotherapy for bone tumours and 43% in orthopaedic patients who already have sore skin when the cast is applied (grade 1 lesion) to the heel. DESIGN: Controlled clinical trial. METHODS: From November 2007-January 2009, all consecutive subjects requiring lower limb casts having undergone chemotherapy and/or presenting heel soreness received polyurethane foam in contact with the skin of the heel before applying the cast. The results were compared with those of patients with the same risk factors but were not administered the foam and were enrolled from May 2005-August 2006. RESULTS: In total, 156 patients were enrolled, 85 in the control group and 71 in the experimental group. In the experimental group, 2 of the 56 patients (3.6%) with sore skin developed a pressure sore compared with 21 of 49 (42.9%) in the control group without polyurethane foam (p < 0.0005). In the experimental group, one of the 24 patients (4.2%) patients undergoing chemotherapy developed a pressure sore compared with 18 of 54 (33.3%) in the control group (p = 0.005). CONCLUSIONS: Placing polyurethane foam in contact with the skin of the heel inside a plaster cast prevents the formation of pressure sores. RELEVANCE TO CLINICAL PRACTICE: This study provides evidence that using polyurethane foam to prevent sores even inside plaster casts in populations at most risk is a simple and cost-effective strategy and decreases the discomfort, pain and risks in these patients.

Nightmare disorder and REM sleep behavior disorder in inflammatory arthritis: Possibility beyond neurodegeneration.

OBJECTIVES: To investigate the prevalence of REM sleep behavior disorder (RBD) in patients with inflammatory arthritis (IA) to ascertain if RBD could be an internal red flag signaling a fluctuating state of inflammation based on the theory of "protoconsciousness". MATERIALS & METHODS: One hundred and three patients with a confirmed diagnosis of IA were consecutively recruited. The patients underwent general (IA activity, functional status, laboratory tests) and neurological evaluations. A neurologist investigated RBD and REM sleep parasomnias in a semi-structured interview. Sleep quality was assessed with the Pittsburgh Sleep Quality Index, while the risk of obstructive sleep apnea syndrome (OSAS) was evaluated with the Berlin questionnaire. Beck Depression Inventory II and State-Trait Anxiety Inventory investigated depression and anxiety. RESULTS: Patients had a mean age of 53.7 ± 14.6 years, 65% were women; 57.3% were in a clinically active phase of IA. Two women fulfilled ICSD-3 criteria for RBD appearing 11 years after and 20 years before IA onset respectively. 31 patients scored positive for nightmare disorder (ND), 8 for recurrent isolated sleep paralysis. 65 (63.1%) patients reported poor sleep quality and 25 (24.3%) resulted at high risk for OSAS. 32 (31.0%) patients scored positively for depression or anxiety. CONCLUSIONS: The prevalence of RBD in patients with IA did not differ from that in the general population, whereas ND presented a 2-fold increased prevalence. Whether RBD can be considered a red flag signaling an internal danger remains an open question, while ND may be a new player in this intriguing relation.

Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study.

Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2'-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor beta, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor beta (VEGFbeta)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor beta, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFbeta can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFbeta, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

Radiographic involvement of metacarpophalangeal and radiocarpal joints in hand osteoarthritis.

To evaluate, by means of a longitudinal study, radiographic involvement of metacarpophalangeal and radio-carpal joints in hand osteoarthritis, its relationship with erosive disease and its progression, 368 patients with hand osteoarthritis were enrolled. All patients underwent hand X-rays. On the basis of the presence of central erosions in interphalangeal joints, patients were divided into three groups: 0-no central erosions, 1-one joint with central erosion, and 2-two or more joints with central erosions. A longitudinal study on 44 patients and nine normal controls, whose X-rays were available after 3.9 years, was performed. The radiological involvement of metacarpophalangeal and radio-carpal joints was evaluated using Kellgren-Lawrence and OARSI scores. Low number of joints showed Kellgren-Lawrence values ≥2 group 0, 42/1290 (3.3%); group 1, 10/410 (2.4%); and group 2, 36/1980 (1.8%). Low score values were obtained for all radiographic items. Only metacarpophalangeal joint space narrowing score showed significant increase from groups 0 to 2. Subsequent adjustment for age, gender, and BMI did not confirm the statistical significance. Marginal erosions were rarely found (6.7% of joints). Metacarpophalangeal and radio-carpal radiographic per patient scores significantly worsened at follow-up, but no significant increase in joints with Kellgren-Lawrence score ≥2 was found. In normal controls, no significant radiographic worsening was found. Only a minority of metacarpophalangeal joints shows a Kellgren-Lawrence value ≥2. Metacarpophalangeal and to lesser extent radiocarpal joints had significant worsening at follow-up. Metacarpophalangeal joint involvement in hand osteoarthritis is mild but progressive. Radiocarpal involvement is negligible.

Transvaginal evisceration after hysterectomy: is vaginal cuff closure associated with a reduced risk?

OBJECTIVE: To evaluate the overall incidence of transvaginal evisceration following hysterectomy and to assess the risk associated with indication, route of surgery, age and vaginal cuff closure technique. MATERIALS AND METHODS: A database was used to identify all patients undergoing hysterectomy from 1995 to 2001 at our institution and all the patients admitted for vaginal evisceration during the same period. Each vaginal evisceration was analyzed for time of onset, trigger event, presenting symptoms, details of prolapsed organs and type of repair surgery. RESULTS: Of the 3593 patients enrolled in the study, 63.5% underwent abdominal hysterectomy, 33.0% vaginal hysterectomy, and 3.5% laparoscopic hysterectomy. Ten patients (0.28%) presented to the emergency room with vaginal evisceration. No statistical differences in evisceration rates were seen according to the route of surgery. No differences were found between the 1440 patients who had closure of the vaginal cuff and the 2153 who had an unclosed cuff closure technique. CONCLUSIONS: Our data suggest that, in young patients, sexual intercourse is to be considered the main trigger event before the complete healing of the vaginal cuff while, in elderly patients, the evisceration is a spontaneous event. Uterine prolapse was not associated with a higher rate and the route of surgery or vaginal cuff closure technique did not influence the dehiscence rate.

Rehabilitation Complexity Scale: Italian translation and transcultural validation.

PURPOSE: The aim of the present study was translation, cultural adaption and validation of the extended version 12 of the Rehabilitation Complexity Scale (RCS-E) in a sample of patients with stroke and total hip replacement. METHOD: The cross-cultural validation required RCS-E forward-backward translation, revision by an expert committee and its application in an Intensive Rehabilitation setting through a retrospective collection of data from clinical records. The evaluation of the psychometric properties was carried out by analyzing the correlations between RCS-E score and other measures (Functional Independence Measure, Braden, Morse, Cumulative Illness Rating Scale) and the assessment of reliability in terms of reproducibility (inter-observer agreement) and repeatability (intra-observer agreement). RESULTS: The backward and forward processes of translation of the scale did not create problems of interpretation of terms. Some adaptation was required for the items nursing (N), medical care (M) and therapeutic intensity (TI) due to differences on the national health system structure. The Italian version of the scale proved to be valid, reliable with high reproducibility and repeatability. CONCLUSIONS: The Italian version RCS-E has been successfully validated, showing good psychometric properties, which partly reproduce the results obtained for the original version. However, some assumption was made for some items thus preventing possible comparison with other countries. IMPLICATIONS FOR REHABILITATION: Admittance at an Intensive Rehabilitation care setting in Italy requires to evaluate the complexity of rehabilitation needs. The Rehabilitation Complexity Scale (RCS-E) has proved to be reliable for assessing clinical complexity and consequently for planning rehabilitation needs. The Italian version of RCS-E has been successfully validated, showing good psychometric properties, which reproduce the results obtained for the original version. The items included in the therapy intensity subscale do not fit the Italian health system rules for intensity of rehabilitation care and needs adaptation.

Is total laparoscopic surgery for endometrial carcinoma at risk of local recurrence? A long-term survival.

BACKGROUND: Loco-regional recurrences after laparotomic surgery for early endometrial carcinoma have an incidence of 3-8%. This study examined the pattern of recurrences and survival after full laparoscopic hysterectomy. PATIENTS AND METHODS: Between January 1997 and December 2002, 113 consecutive patients with pre-operative Stage I endometrial cancer, self-referred to two different surgical teams, were treated by the laparoscopic approach by one team and by the laparotomic approach by the other team. RESULTS: Nineteen patients were treated by total laparoscopic hysterectomy (TLH) by the endoscopic group, and 94 were treated by total abdominal hysterectomy (TAH) by the oncologic group. Sixteen patients (84.2%) in the laparoscopic group and 79 patients (84.0%) in the laparotomic group had Stage I disease. The mean age and mean weight did not differ in the two groups. With a mean follow-up of 52.2 months for the TLH group and 43.6 months for the TAH group, one recurrence (5.3%) was observed in the former group and 9 recurrences (10.6%) in the latter group. No significative differences were observed for disease-free survival and overall survival. CONCLUSION: Total laparoscopic hysterectomy does not increase the risk of local recurrence and does not affect survival for patients with early stage endometrial carcinoma.

Measuring functional performance at discharge from hospital after total joint arthroplasty as a pre-requisite for planning early rehabilitation: a prognostic study.

BACKGROUND: The autonomy achieved by discharge after total knee and hip arthroplasty is important for planning early rehabilitation. PURPOSE: Describe functional performance using the Iowa Level of Assistance (ILOA) scale and investigate possible prognostic factors. METHODS: A prospective cohort study design was used. Autonomy at discharge was measured using the ILOA scale. Postoperative factors such as time to remove surgical drains, the length of hospitalization, preoperative physical therapy, and the number of physiotherapy treatments were collected. RESULTS: The sample was composed of 452 patients: 191 men (42.3%) and 261 women (57.7%). The mean ILOA score was 12.34 (SD = 5.4), representing a level of autonomy of 68.4%. Gait speed was the activity with the highest score and it ranged from 0.26 m/s to 0.32 m/s. Based on univariate and multivariate analysis, gender and age were the only significant variables to influence achieving autonomy at discharge. CONCLUSION: The rehabilitative program in its acute phase should be planned with particular attention paid to elderly women, unifying the physiotherapy protocol for total hip arthroplasty (THA) and total knee arthroplasty (TKA), reviewing the modalities of preoperative treatment sessions and with a specific training for the speed gait.

Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study.

Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow-up. The impact of tumor-host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP-2 and to pro-survival proteins NFIB and c-Fos. Kaplan-Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co-overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12-44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor-host endpoints for new biological treatments.

Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.

OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage. MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated. RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.