Sergi Mojal

Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients

The modulation of JAK2 V617F allele burden dynamics was prospectively analysed in 47 patients (26 polycythaemia vera [PV] and 21 essential thrombocythaemia [ET]) treated with first‐line hydroxyurea (HU) and compared with the JAK2 V617F dynamics of a control group of 45 PV and ET patients. A partial molecular response (PMR), according to European Leukaemia Net criteria, was observed in 27/47 (57%) patients. Median time to PMR was 14 months (3–66) with a probability of PMR at 3 years of 57%. A significant decrease in JAK2 V617F allele load was observed at 36 months both in PV and ET patients, being the reduction in PV higher than in ET patients (P = 0·01). A haematocrit ≥0·45 L/L was associated with a higher probability of attaining a PMR (HR:3·4; 95%CI:1·02–11·6, P = 0·04). Control group showed a slight increase of JAK2 V617F allele burden over time. The reduction in the mutated allele load comparing treated patients versus controls was highly significant both in PV and ET, demonstrating a clear effect of HU on the JAK2 V617F allele burden. In conclusion, first‐line HU can attain PMR in more than 50% of newly diagnosed PV and ET patients, with a continuous decrease of the JAK2 V617F allele burden in PV patients during treatment.

HPV Testing by cobas HPV Test in a Population from Catalonia

Background HPV testing in cervical cancer screening has been proposed as an alternative or complementary to cytology in women older than 30 years. However, adequate clinical sensitivity and specificity are crucial for a new test to be implemented. Hybrid Capture 2 (HC2) has proved good clinical performance in selecting women at risk for high-grade intraepithelial lesions with a high sensitivity and specificity. cobas HPV Test has been recently launched and its performance in different clinical settings needs to be determined. Objectives The aim of this study was to evaluate the cobas HPV Test for the detection of cervical HPV infection in a population of women in Catalonia (Spain) using HC2 as a reference. Materials and Methods Cervical liquid cytology samples from 958 women have been studied. Sensitivity was analyzed in 60 samples from patients with a high-grade intraepithelial lesion (≥CIN2) on histology and specificity was determined in 898 samples from women with no ≥CIN2. All cases had HC2 and cobas HPV Test performed. Statistical analyses of sensitivity, specificity and comparison between HC2 and cobas HPV Test by a non-inferiority test were applied. Results Sensitivity of HC2 and cobas HPV Test for detecting ≥CIN2 proved identical (98.3%) while specificity was 85.3% and 86.2% respectively. The non-inferiority test demonstrated that cobas HPV Test surpassed 90% sensitivity and 98% specificity of HC2. Conclusion The cobas HPV Test results fulfilled sensitivity and specificity requirements for HPV based cervical cancer screening and for the triage of minor cytological abnormalities, allowing its introduction in clinical settings.

Angiopoietin-2 is a negative prognostic marker in small cell lung cancer

BACKGROUND Small cell lung cancer (SCLC) is a highly lethal disease due to its chemorefractory nature after initial treatment. Angiogenesis plays an important role in tumor growth, metastasis and chemoresistance. We hypothesized that angiogenesis could predict chemoresistance in SCLC patients and be potentially a therapeutic target in this disease. METHODS Serum samples from forty-three SCLC patients were prospectively obtained at diagnosis, response evaluation and progression. Angiogenesis-related cytokines (Angiopoietin-2, VEGF-A, C and D) were simultaneously quantified by Luminex Technology. Clinical data were prospectively recorder. RESULTS Significantly higher concentration of angiogenesis-related cytokines were found in SCLC patients at diagnosis compared to healthy volunteers. High baseline serum concentration of Angiopoietin-2 (sAngiopoietin-2) were associated with a worse overall survival (p=0.006) and remained independently associated with survival in the multivariate analysis (p=0.008). In addition, sAngiopoietin-2 significantly increased at progression when compared to baseline. CONCLUSION These data provide novel evidence on a role of sAngiopoietin-2 in the adverse clinical behavior of SCLC and could be a potential therapeutic target in this disease.

Renal volume and cardiovascular risk assessment in normotensive autosomal dominant polycystic kidney disease patients

Abstract Cardiovascular disease, closely related to an early appearance of hypertension, is the most common mortality cause among autosomal dominant polycystic kidney disease patients (ADPKD). The development of hypertension is related to an increase in renal volume. Whether the increasing in the renal volume before the onset of hypertension leads to a major cardiovascular risk in ADPKD patients remains unknown. Observational and cross-sectional study of 62 normotensive ADPKD patients with normal renal function and a group of 28 healthy controls. Renal volume, blood pressure, and renal (urinary albumin excretion), blood vessels (carotid intima media thickness and carotid-femoral pulse wave velocity), and cardiac (left ventricular mass index and diastolic dysfunction parameters) asymptomatic organ damage were determined and were considered as continuous variables. Correlations between renal volume and the other parameters were studied in the ADPKD population, and results were compared with the control group. Blood pressure values and asymptomatic organ damage were used to assess the cardiovascular risk according to renal volume tertiles. Even though in the normotensive range, ADPKD patients show higher blood pressure and major asymptomatic organ damage than healthy controls. Asymptomatic organ damage is not only related to blood pressure level but also to renal volume. Multivariate regression analysis shows that microalbuminuria is only associated with height adjusted renal volume (htTKV). An htTKV above 480 mL/m represents a 10 times higher prevalence of microalbuminuria (4.8% vs 50%, P < 0.001). Normotensive ADPKD patients from the 2nd tertile renal volume group (htTKV > 336 mL/m) show higher urinary albumin excretion, but the 3rd tertile htTKV (htTKV > 469 mL/m) group shows the worst cardiovascular risk profile. Normotensive ADPKD patients show in the early stages of the disease with slight increase in renal volume, higher cardiovascular risk than healthy controls. An htTKV above 468 mL/m is associated with the greatest increase in cardiovascular risk of normotensive ADPKD patients with normal renal function. Early strategies to slow the progression of the cardiovascular risk of these patients might be beneficial in their long-term cardiovascular survival.

Cervista HPV HR Test for Cervical Cancer Screening A Comparative Study in the Catalonian Population

CONTEXT Almost all cervical cancers are related to the human papillomavirus (HPV). Future strategies for cervical cancer screening will be based on HPV detection. The Hybrid Capture 2 (HC2) test is currently the most widely used method to screen for HPV. OBJECTIVE To test the performance of the Cervista HPV HR test for cervical screening. DESIGN We examined 875 cervical samples by HC2 and Cervista. Of these, 64 were high-grade cervical intraepithelial neoplasia (CIN 2+) cases and were used to test the sensitivity of the assay. The remaining 811 were non-CIN 2+ cases, which were used to compare specificity. The noninferiority score test was used, with at least 0.90 for sensitivity and 0.98 for specificity and with a κ value of 0.7. RESULTS Sensitivity and specificity were, respectively, 100% and 86.4% for the HC2 test, and 98.4% and 85.2% for the Cervista test. The agreement between the two assays was 91.7% (802 of 875; κ = 0.743; 95% confidence interval, 0.688-0.798). The noninferiority score test (relative sensitivity of 90%, T = 2.85, P = .002; and relative specificity of 98%, T = 2.75, P = .003) demonstrated that the Cervista results were not inferior to those of the HC2 test. Intralaboratory and interlaboratory reproducibility was determined by evaluating 513 and 507 samples, respectively. These reproducibilities showed κ values of 0.886 (95% confidence interval, 0.845-0.927) and 0.907 (95% confidence interval, 0.886-0.948), respectively. CONCLUSIONS Our results demonstrate that the Cervista HPV HR test shows the same specificity as the HC2 assay. We therefore conclude that the Cervista HPV HR test is suitable for cervical cancer screening purposes.

Factores predictivos de nefropatía no diabética en pacientes diabéticos: Utilidad de la biopsia renal

BACKGROUND AND OBJECTIVES Diabetic renal lesions can only be diagnosed by kidney biopsy. These biopsies have a high prevalence of non-diabetic lesions. The aims of the study were to determine the predictability of non-diabetic nephropathy (NDN) in diabetics and study differences in survival and renal prognosis. In addition, we evaluated histological lesions and the effect of proteinuria on survival and renal prognosis in patients with diabetic nephropathy (DN). MATERIAL AND METHODS A descriptive, retrospective study of kidney biopsies of diabetics between 1990 and 2013 in our centre. RESULTS 110 patients were included in the study: 87 men (79%), mean age 62 years (50-74), mean serum creatinine 2.6mg/dl (0.9-4.3) and proteinuria 3.5g/24hours (0.5-6.5). 61.8% showed NDN, 34.5% showed DN and 3,6% showed DN+NDN. The most common NDN was IgA nephropathy (13,2%). In the multivariate analysis, creatinine (OR: 1.48, 1.011-2.172, p=0.044), proteinuria/24hours (OR: 0.813, 0.679-0.974, p=0.025), duration of diabetes (OR: 0.992, 0.987-0.998, p=0.004), age (OR: 1.068, 95% CI: 1.010-1.129, p=0.022), and diabetic retinopathy (OR: 0.23, 0.066-0.808, p=0.022) were independently associated with NDN. We did not find any differences in survival or renal prognosis. Concerning patients with DN, increased nodular mesangial expansion (p=0.02) and worse renal prognosis (p=0.004) were observed in nephrotic proteinuria as compared to non-nephrotic proteinuria. We did not find differences in patient survival. CONCLUSIONS The most common cause of NDN was IgA nephropathy. Higher creatinine levels, shorter duration of diabetes, absence of diabetic retinopathy, lower proteinuria, and older age were risk factors for NDN. Patients with DN and nephrotic-range proteinuria had worse renal prognosis.

Bloqueo del sistema renina-angiotensina-aldosterona en pacientes con enfermedad renal diabética avanzada

BACKGROUND AND OBJECTIVES Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. MATERIALS AND METHODS Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. RESULTS Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. CONCLUSIONS Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m2. In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade.