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1.  Asymmetric dimethylarginine predicts survival in the elderly 
Age  2013;35(6):2465-2475.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase implicated in several age-related biological mechanisms such as telomere shortening and cell senescence. We tested the hypothesis that ADMA blood level is an independent predictor of mortality in elderly. This is a longitudinal population-based cohort study. Participants are a representative cohort of 1,025 men and women (age range 65–102 years) living in Chianti area, Tuscany, Italy. The plasma ADMA was measured by liquid chromatography–tandem mass spectrometry. During the follow-up (95 ± 32 months), 384 individuals died, of whom 141 (37 %) died of cardiovascular (CV) causes. In adjusted analyses, the plasma ADMA was the strongest predictor of all-cause mortality (HR (0.1 μMol/L) 1.26, 95 % CI 1.10–1.44, P < 0.001) with a non-significant trend for CV mortality (HR 1.22, P = 0.07). The predictive effect of the ADMA level on mortality was statistically significant among participants with low to low-normal l-arginine levels (≤60 μMol/L), but not in those with l-arginine >60 μMol/L. Notwithstanding the association of ADMA with all-cause mortality was robust, this biomarker failed to add predictive power to a simple model based on the risk factors in the elderly (area under the ROC curve 0.85 ± 0.01 vs. 0.84 ± 0.01). ADMA is a strong independent predictor of mortality in the older population, and l-arginine modifies the effect of ADMA on survival. The mechanisms for this association should be targeted by future studies.
PMCID: PMC3824988  PMID: 23584888
ADMA; Elderly; Cardiovascular risk factor; Survival; Population study
2.  A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur guided by K-wires previously inserted under CT-guide: a case report 
BMC Surgery  2014;14:52.
In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature.
Case presentation
A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy.
Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient.
PMCID: PMC4137725  PMID: 25123066
Tumour resection; Osteotomy; Low-grade chondrosarcoma; Low-grade bone tumour; Wide margin; Navigation computer assisted
3.  The dysfunctional endothelium in CKD and in cardiovascular disease: mapping the origin(s) of cardiovascular problems in CKD and of kidney disease in cardiovascular conditions for a research agenda 
Endothelial dysfunction resulting in disintegration of vascular structure and function is a key element in the progression of chronic kidney disease (CKD). Many risk factors—traditional and non-traditional—are thought to have a role in the progression and development of cardiovascular disease (CVD) in patients with CKD. However, many risk factors await definitive confirmation of their clinical relevance obtained from intervention trials. Moreover, the investigation of the relative contribution of these factors to the twin-risk problem of CVD and progression in patients with CKD is one of the most important future challenges for nephrologists.
PMCID: PMC4089605  PMID: 25018895
biomarkers; cardiovascular disease; chronic kidney disease; endothelium
4.  The complexity of the cardio–renal link: taxonomy, syndromes, and diseases 
Bidirectional mechanisms exist that link diseases affecting the heart and kidney. This link is complex and remains poorly understood; therefore, charting the shared territory of cardiovascular (CV) and renal medicine poses major problems. Until now, no convincing rationale for delineating new syndromes existed. The multiple connections of the arterial system and the heart and kidney with other systems, from energy and protein balance to the musculoskeletal, clearly require special focus and rigorous framing. Nephrologists have yet to fully understand why the application of dialysis has had only limited success in halting the parallel burdens of CV and non-CV death in patients with end-stage renal disease. Cardiologists, intensivists, and nephrologists alike should settle whether and when extracorporeal ultrafiltration benefits patients with decompensated heart failure. These sparse but interconnected themes spanning from the basic science–clinical transition phase to clinical science, epidemiology, and medical technology already form the basis for the young discipline of ‘CV and renal medicine'.
PMCID: PMC4089616  PMID: 25028622
cardio-renal; cardiovascular risk; CKD; death; ESRD; progression of CKD
5.  Cardiovascular and renal medicine, an expanding territory 
PMCID: PMC4089640  PMID: 25028621
6.  The lingering dilemma of arterial pressure in CKD: what do we know, where do we go? 
Despite many advances in the management of hypertensive chronic kidney disease (CKD) patients, both on and off dialysis, there exist several gaps in our knowledge. Although the modern techniques to measure blood pressure (BP) indirectly have been available for a long time, among those with CKD, how to best assess hypertension and the level to which it should be lowered are mired in controversy. Other controversial areas relate to a lack of a consensus definition of hypertension among hemodialysis patients, uncertainty in the definition and assessment of volume excess, and the lack of adequately powered randomized trials to evaluate the level to which BP can be lowered in those on dialysis. This review discusses the limitations of the available evidence base and suggests areas for future research. Suggestions include evaluation of techniques to assess volume, randomized trials to target different levels of BP among hypertensive hemodialysis patients, evaluation of ambulatory BP monitoring, and non-pharmacological means to lower BP in CKD. It is hoped that among patients with CKD these data will improve the dismal cardiovascular outcomes.
PMCID: PMC4089679  PMID: 25018898
ambulatory blood pressure; cardiovascular disease; CKD; hypervolemia; outcome studies; risk factors
7.  Arterial aging and arterial disease: interplay between central hemodynamics, cardiac work, and organ flow—implications for CKD and cardiovascular disease 
Cardiovascular disease is an important cause of morbidity and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). All epidemiological studies have clearly shown that accelerated arterial and cardiac aging is characteristic of these populations. Arterial premature aging is heterogeneous. It principally involves the aorta and central capacitive arteries, and is characterized by preferential aortic stiffening and disappearance of stiffness/impedance gradients between the central and peripheral arteries. These changes have a double impact: on the heart, upstream, with left ventricular hypertrophy and decreased coronary perfusion; and, downstream, on renal and brain microcirculation (decrease in glomerular filtration and cognitive functions). Multifactorial at origin, the pathophysiology of aortic ‘progeria' and microvascular disorders in CKD/ESRD is not well understood and should be the focus of interest in future studies.
PMCID: PMC4089718  PMID: 25018896
aging; arteriosclerosis; arterial stiffness; end-stage renal disease; pressure waves
8.  Cardiovascular and non-cardiovascular mortality in dialysis patients: where is the link? 
Over the past decade, the research agenda in dialysis has been dominated by studies on risk factors associated with cardiovascular mortality. It has now become increasingly clear that in dialysis patients, non-cardiovascular causes of death are increased to the same extent as cardiovascular mortality, and therefore research efforts in this area deserve an equally prominent place on the nephrology research agenda. As previous research has suggested an association between cardiovascular disease and infections, more research on potential links between the causal pathways of cardiovascular events and infections is also warranted.
PMCID: PMC4089722  PMID: 25028623
cardiovascular disease; cardiovascular mortality; dialysis; mortality; non-cardiovascular mortality; renal replacement therapy
9.  Major pathways of the reno–cardiovascular link: the sympathetic and renin–angiotensin systems 
Chronic kidney disease is often characterized by enhanced activity of the renin–angiotensin system (RAS) and the sympathetic nervous system. Independent of their effect on blood pressure, these systems also contribute to the pathogenesis of both structural and functional cardiovascular abnormalities and contribute importantly to clinical outcome. There is much evidence that the diseased kidneys are of central importance in the pathogenesis of both abnormalities. Inhibitors of the RAS also reduce sympathetic overactivity. Future research should be aimed at addressing the pathophysiological mechanisms causing the enhanced activities. Given the fact that even a small kidney lesion can cause enhanced activity of the RAS and the sympathetic nervous system, it is likely that these pathophysiological mechanisms are operational in more disease conditions, including essential hypertension, heart failure, and obesity/metabolic syndrome.
PMCID: PMC4089777  PMID: 25018897
chronic kidney disease; hypertension; renin angiotensin; sympathetic activity
11.  Joint effect of insulin signalling genes on cardiovascular events and on whole body and endothelial insulin resistance 
Atherosclerosis  2012;226(1):140-145.
Insulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity.
Design and Setting
1. We first studied, incident cardiovascular events (a composite endpoint comprising myocardial infarction -MI-, stroke and cardiovascular death) in 733 patients (2,186 person-years, 175 events). 2. In a replication attempt, age at MI was tested in 331 individuals. 3. OGTT-derived insulin sensitivity index (ISI) was assessed in 829 individuals with fasting glucose < 126 mg/dl. 4. NOS activity was measured in 40 strains of human vein endothelial cells (HUVECs).
1. Risk variants jointly predicted cardiovascular events (HR=1.181; p=0.0009) and, when added to clinical risk factors, significantly improved survival C-statistics; they also allowed a significantly correct reclassification (by net reclassification index) in the whole sample (135/733 individuals) and, even more, in obese patients (116/204 individuals). 2. Risk variants were jointly associated with age at MI (p=0.006). 3. A significant association was also observed with ISI (p=0.02). 4. Finally, risk variants were jointly associated with insulin-stimulated NOS activity in HUVECs (p=0.009).
Insulin signaling genes variants jointly affect cardiovascular disease, very likely by promoting whole body and endothelium-specific insulin resistance. Further studies are needed to address whether their genotyping help identify very high-risk patients who need specific and/or more aggressive preventive strategies.
PMCID: PMC3529747  PMID: 23107043
genetic susceptibility; non synonymous polymorphism; insulin sensitivity; insulin dependent endothelial function
12.  Estimated Glomerular Filtration Rate, All-Cause Mortality and Cardiovascular Diseases Incidence in a Low Risk Population: The MATISS Study 
PLoS ONE  2013;8(10):e78475.
Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far.
Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD.
Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula.
At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m2 and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73m2, respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors.
These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.
PMCID: PMC3797762  PMID: 24147135
13.  Longitudinal association of body mass index and waist circumference with left ventricular mass in hypertensive predialysis chronic kidney disease patients 
Nephrology Dialysis Transplantation  2013;28(Suppl 4):iv136-iv145.
This study aimed to investigate the association of both body mass index (BMI) and waist circumference (WC) with left ventricular mass (LVM) in hypertensive predialysis chronic kidney disease (CKD) patients.
From 2004 to 2005, 206 consecutive incident adult patients from the outpatient CKD clinics of two hospitals in Greece were included. Inclusion criteria were the presence of CKD and hypertension. BMI (kg/m2), WC (cm) and LVM (g) were assessed annually for 3 years.
The mean age was 68.1 years, mean BMI 29.1 kg/m2 and mean WC was 103.7 cm. The median LVM was 245.7 g (n = 179). In the cross-sectional data, linear regression models showed that WC {β = 1.2 [95% confidence interval (CI) 0.15; 2.3]}, and not BMI [β = 2.1 (95% CI: −0.70; 4.8)], was significantly associated with LVM. After adjustment for age, sex, primary renal disease, smoking and history of cardiovascular disease, both BMI [β = 4.7 (95% CI: 2.0; 7.4] and WC [β = 1.2 (95% CI: 0.14; 2.3)] were significantly associated with LVM. These associations were pronounced in CKD stage 1–3, but not in CKD stage 4–5. In the longitudinal analysis, linear mixed models adjusting for confounders showed that both an increase in BMI [β = 2.9 (95% CI: 0.74; 5.1)] and an increase in WC [β = 1.1 (95% CI: 0.28; 1.8)] were significantly associated with an increase in LVM.
In hypertensive predialysis CKD patients, both BMI and WC were associated with LVM in CKD stage 1–3, but not in CKD stage 4–5. In the longitudinal analysis, both an increase in BMI and WC were associated with an increase in LVM. Future studies should focus on mechanisms responsible for the associations between anthropometric variables and LVM.
PMCID: PMC3814229  PMID: 24049104
body mass index; chronic kidney disease; hypertension; left ventricular mass; waist circumference
14.  Homoarginine and Mortality in Pre-Dialysis Chronic Kidney Disease (CKD) Patients 
PLoS ONE  2013;8(9):e72694.
Background and Aims
Homoarginine, a precursor of nitric oxide, is an inverse predictor of death in dialysis patients and in subjects with cardiovascular disease and normal kidney function but its relationship with clinical outcomes in chronic kidney disease (CKD) patients not yet on dialysis is unknown.
Design, setting, participants and measurements
We enrolled 168 consecutive predialysis CKD patients (Age: 70±11 yrs; 26% Diabetics; eGFR 34±18 ml/min/1.73 m2) referred to a tertiary care centre and measured laboratory data on kidney function and cardiovascular risk factors. We modeled progression to dialysis or death as a function of homoarginine, using Cox’s regression, accounting for clinical characteristics, baseline levels of kidney function, and markers of inflammation.
On crude and adjusted analyses homoarginine was directly associated with the eGFR and patients with more compromised renal function exhibited lower homoarginine levels. Furthermore homoarginine was also independently related to L-arginine, serum albumin and body mass index, and inversely related to proteinuria, C-reactive protein and age. During the study (follow up median time 4 years, inter-quartile range 1.7 to 7.0 years) 56 patients started dialysis and 103 died and homoarginine was a strong inverse predictor of the incidence rate of both outcomes (P = 0.002 and P = 0.017).
Homoarginine declines with advancing renal disease and is inversely related to progression to dialysis and mortality. The nature of the link between homoarginine and clinical outcomes is amenable to testing in clinical trials.
PMCID: PMC3762798  PMID: 24023762
15.  Pulmonary Congestion and Physical Functioning in Peritoneal Dialysis Patients 
♦ Purpose: Decline in physical function is commonly observed in patients with kidney failure on dialysis. Whether lung congestion, a predictable consequence of cardiomyopathy and fluid overload, may contribute to the low physical functioning of these patients has not been investigated.
♦ Methods: In 51 peritoneal dialysis (PD) patients, we investigated the cross-sectional association between the physical functioning scale of the Kidney Disease Quality of Life Short Form (KDQOL-SF: Rand Corporation, Santa Monica, CA, USA) and an ultrasonographic measure of lung water recently validated in dialysis patients. The relationship between physical functioning and lung water was also analyzed taking into account the severity of dyspnea measured using the New York Heart Association (NYHA) classification currently used to grade the severity of heart failure.
♦ Results: Evidence of moderate-to-severe lung congestion was evident in 20 patients, and this alteration was asymptomatic (that is, NHYHA class I) in 11 patients (55%). On univariate analysis, physical functioning was inversely associated with lung water (r = -0.48, p < 0.001), age (r = -0.44, p = 0.001), previous cardiovascular events (r = -0.46, p = 0.001), and fibrinogen (r = -0.34, p = 0.02). Physical functioning was directly associated with blood pressure, the strongest association being with diastolic blood pressure (r = 0.38, p = 0.006). The NYHA class correlated inversely with physical functioning (r = -0.51, p < 0.001). In multiple regression analysis, only lung water and fibrinogen remained independent correlates of physical functioning. The NYHA class failed to maintain its independent association.
♦ Conclusions: This cross-sectional study supports the hypothesis that symptomatic and asymptomatic lung congestion is a relevant factor in the poor physical functioning of patients on PD.
PMCID: PMC3524861  PMID: 22942271
KDQOL-SF; physical functioning; lung comets; NYHA class
16.  Cultural adaptation and validation of the “Kidney Disease and Quality of Life - Short Form (KDQOL-SF™) version 1.3” questionnaire in Egypt 
BMC Nephrology  2012;13:170.
Health Related Quality of Life (HRQOL) instruments need disease and country specific validation. In Arab countries, there is no specific validated questionnaire for assessment of HRQOL in chronic kidney disease (CKD) patients. The aim of this study was to present an Arabic translation, adaptation, and the subsequent validation of the kidney disease quality of life-short form (KDQOL-SFTM) version 1.3 questionnaire in a representative series of Egyptian CKD patients.
KDQOL-SFTM version 1.3 was translated into Arabic by two independent translators, and then subsequently translated back into English. After translation disparities were reconciled, the final Arabic questionnaire was tested by interviewing 100 pre-dialysis CKD (stage 1-4) patients randomly selected from outpatients attending the Nephrology clinic at the Main Alexandria University Hospital. Test re-test reliability was performed, with a subsample of 50 consecutive CKD patients, by two interviews 7 days apart and internal consistency estimated by Cronbach’s α. Discriminant, concept, and construct validity were assessed.
All items of SF-36 met the criterion for internal consistency and were reproducible. Of the 10 kidney disease targeted scales, only three had Cronbach’s α <0.7: quality of social interaction (0.23), work status (0.28), and cognitive function (0.60). All disease specific scales were reproducible. Results from discriminant validity showed that the study questionnaire could discriminate between patients’ subgroups. As for concept validity, the correlation between all domains of the questionnaire with overall health ratewas significant for all domains except for the work status, sexual function, emotional wellbeing, and role emotional. Furthermore, the correlation between the disease specific domains and the two composite summaries of SF-36 (physical and mental composite summaries) was significant for all domains except for sexual function with mental composite summary. Construct validity was indicated by the observation that the majority of the domains of the kidney disease targeted scale of KDQOL-SFTM 1.3 were significantly inter-correlated. Finally, principal component analysis of the kidney disease targeted scale indicated that this part of the questionnaire could be summarized into 10 factors that together explained 70.9% of the variance.
The results suggest that this Arabic version of the KDQOL-SFTM 1.3 questionnaire is a valid and reliable tool for use in Egyptian patients with CKD.
PMCID: PMC3583144  PMID: 23237591
Chronic kidney disease; Egypt; Health-related quality of life; KDQOL-SFTM 1.3; Questionnaire validation
17.  Pro-inflammatory cytokines and bone fractures in CKD patients. An exploratory single centre study 
BMC Nephrology  2012;13:134.
Pro-inflammatory cytokines play a key role in bone remodeling. Inflammation is highly prevalent in CKD-5D patients, but the relationship between pro-inflammatory cytokines and fractures in CKD-5D patients is unclear. We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients.
In 100 CKD-5D patients (66 on HD, 34 on CAPD; males:63, females:37; mean age: 61 ± 15; median dialysis vintage: 43 months) belonging to a single renal Unit, we measured at enrolment bone metabolic parameters (intact PTH, bone and total alkaline phosphatase, calcium, phosphate) and inflammatory cytokines (TNF-α, IL-6, CRP). Patients were followed-up until the first non traumatic fracture.
During follow-up (median: 74 months; range 0.5 -84.0) 18 patients experienced fractures. On categorical analysis these patients compared to those without fractures had significantly higher intact PTH (median: 319 pg/ml IQ range: 95–741 vs 135 pg/ml IQ: 53–346; p = 0.04) and TNF-α levels (median: 12 pg/ml IQ: 6.4-13.4 vs 7.8 pg/ml IQ: 4.6-11; p = 0.02). Both TNF-α (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) and intact PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005) predicted bone fractures on univariate Cox’s regression analysis. In restricted (bivariate) models adjusting for previous fractures, age, sex and other risk factors both PTH and TNF-α maintained an independent association with incident fractures.
In our bivariate analyses TNF-α was significantly associated with incident fractures. Analyses in larger cohorts and with adequate number of events are needed to firmly establish the TNF α -fracture link emerged in the present study.
PMCID: PMC3472278  PMID: 23043229
Bone fractures; CKD; Dialysis; Hyperparathyroidism; TNF-alpha; Inflammation
18.  Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial 
Nephrology Dialysis Transplantation  2012;27(9):3594-3600.
Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes.
Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients).
CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta2 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta2 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170).
In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.
PMCID: PMC3433772  PMID: 22622452
ESA resistance; haemoglobin; haemodialysis; online haemofiltration; online haemodiafiltration
19.  Arthroscopic guided biopsy and radiofrequency thermoablation of a benign neoplasm of the tibial spines area: a treatment option 
Lesions located in the area of the tibial spines are rare. In most cases, treatment follows histological diagnosis, but when imaging and clinical data are considered to be "very" characteristic for benign lesions, such as chondroblastoma or osteoid osteoma, treatment may be performed without biopsy. Traditional curettage requires opening the joint, which presents a high risk of contamination of the joint itself and surrounding structures, such as the popliteal area, with possible contamination of the neurovascular bundle when performing curettage with the posterior approach. In this case, the re-excision of a local recurrence would be extremely difficult.
We describe a technique using arthroscopic guidance for radiofrequency thermoablation of a benign lesion in the tibial spines area. We report on an illustrative case. The patient so treated, reported immediate relief from the pain, and after two weeks, was free of pain. The biopsy performed before the treatment confirmed the radiological diagnosis of chondroblastoma. At one year of follow-up, the patient is without pain, with a 0-130°range of motion, has no activity limitations and is apparently free of disease.
This technique allows a radiofrequency thermoablation of a lesion in the tibial spines area and in the posterior tibial surface to be performed without opening the joint, monitoring the tibial plateau surface, probably decreasing the risk of cartilage damage. Unfortunately, in the case presented, the high pressure from the arthroscopy's pump broke the tibial plateau surface creating a communication to the tibial tunnel used for thermoablation.
PMCID: PMC3349528  PMID: 22475175
Radiofrequency thermoablation; Tibial spines; Osteoid osteoma; Chondroblastoma; Arthroscopic guided biopsy; I declare that we have no commercial interest in the subject under study and that we have not received any financial or material support
20.  The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals 
Diabetes  2011;60(3):1000-1007.
Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals.
A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; n = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (n = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (n = 169 from Italy, n = 170 from the U.S.).
Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80–2.70) in GHS, 2.31 (95% CI 1.22–4.34) in TVAS, and 1.36 (95% CI 0.88–2.10) in CREED, and 1.56 (95% CI 1.15–2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, P = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (P = 0.035 for interaction).
The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding.
PMCID: PMC3046818  PMID: 21282363
21.  Ectopic primary type A thymoma located in two thoracic vertebras: a case report 
BMC Cancer  2010;10:322.
The thymus arises in the ventral portion of the third and fourth pharyngeal pouch. It descends into the anterior mediastinum at 6th week of gestation. Any errors occurring during this process can cause dissemination of aberrant nodules that are responsible for most atypical thymomas.
Case Presentation
The authors report a unusual case of type-A thymoma located in D10 and D11 vertebral bodies.
The histology showed a uniform growth of short, spindle shaped, mitotically inactive cells. A few small, normal lymphocytes were seen scattered or in small groups. The immunohistochemical investigation for neuroectodermal, neuroendocrine, vascular and muscular markers were negative. It also confirmed the presence of CD3+, CD5+ T lymphocytes and the absence of immature T-lymphocyte markers.
The case described shows a thymic hystogenesis for spindle cell tumours. To our knowledge no other cases of vertebral thymomas have been described in international literature.
PMCID: PMC2903530  PMID: 20573206
22.  Mazabraud’s syndrome: a new case and review of the literature 
International Orthopaedics  2008;33(3):605-610.
The association between muscular myxomas and fibrous dysplasia is a rare condition known as Mazabraud’s syndrome, as reported by Henschen (Verh Dtsch Ges Pathol 21:93–97, 1926) and Mazabraud A and Girard (Rev Rhum Mal Osteoartic 24(9–10):652–659, 1957). We report a case of a 32-year-old woman with multiple myxomas in her right thigh and monomelic fibrous dysplasia. A review of the international literature referring to 67 cases to date was carried out. The syndrome is characterised by the following features: females are twice as likely to be affected as males; the lower limbs are the most frequently affected, fibrous dysplasia is more common in the femur and the pelvis and myxomas in the quadriceps muscle; myxoma is multiple in more than 70% of cases. Although there has never been any continuity between tumours and bone lesions, a significant correlation between dysplastic bone and myxoma has been revealed.
PMCID: PMC2903125  PMID: 18214477
23.  Chordoma: clinical characteristics, management and prognosis of a case series of 25 patients 
BMC Cancer  2010;10:22.
Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported.
We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008.
Twenty-five consecutive patients with sacral (11 patients), spine (13 patients), and skull base (1 patient) chordoma went to our observation. Six patients (24%) had primary disease, 14(56%) a recurrent disease, and 5(20%) a metastatic spreading. Surgery was the primary option for treatment in 22 out of 25 patients. Surgical margins were wide in 5 (23%) and intralesional in 17(77%) patients; 3 out of 4 in-house treated patients obtained wide margins. After first surgery, radiotherapy (protons or high-energy photons) were delivered to 3 patients. One out of the 5 patients with wide margins is still without evidence of disease at 20 months from surgery; 2 patients died without evidence of disease after 3 and 36 months from surgery. Sixteen out of 17 (94%) patients with intralesional margins underwent local progression at a median time of 18 months with a 2-year local progression-free survival of 47%. The 5-year metastasis-free survival rate was 78.3%. Seventeen patients with locally advanced and/or metastatic disease expressing platelet-derived growth factor receptor (PDGFR) β were treated with imatinib mesylate. A RECIST stabilization of the disease was the best response observed in all treated cases. Pain relief with reduction in analgesics use was obtained in 6 out of 11 (54%) symptomatic patients. The 5- and 10-year survival rates of the entire series of patients were 76.7 and 59.7%, respectively.
Despite progress of surgical techniques and the results obtained with targeted therapy, more effort is needed for better disease control. Specific experience of the multidisciplinar therapeutic team is, however, essential to succeed in improving patients' outcome.
PMCID: PMC2828414  PMID: 20109225
24.  An osteoporotic hip fracture in a 14-year-old girl undergoing chemotherapy and operated for knee osteosarcoma 
Non-weight-bearing, pre- and postsurgical immobilization, neoadjuvant and adjuvant chemotherapy are known to act on bone turnover, causing osteoporosis over short and long time periods. Treatment of fracture insurgence is very difficult because it really depends on being able to choose the right time (i.e., when immunodeficiency is less important). We report a case of spontaneous neck femur fracture during adjuvant chemotherapy in a young girl treated with resection and prosthesis reconstruction for distal femur osteosarcoma. Possible prevention and the correct approach and surgical timing are emphasized considering immunodeficiency following chemotherapy.
PMCID: PMC2744736  PMID: 19644649
Chemotherapy osteoporosis; Juvenile osteoporosis; Osteoporosis fracture children; Methotrexate complications
25.  The 2007 ERA-EDTA Registry Annual Report—a Précis 
NDT Plus  2009;2(6):514-521.
PMCID: PMC2779783  PMID: 19936072
incidence; prevalence; renal replacement therapy; survival

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