RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

Background High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. Methods Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m 2 and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. Results Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P P = .009). The best threshold for CI-AKI prevention was a mean intraprocedural phase UFR ≥450 mL/h (area under curve 0.62, P = .009, sensitivity 80%, specificity 46%). Performance of percutaneous coronary intervention (hazard ratio [HR] 4.13, 95% CI 1.81-9.10, P P = .012), and total furosemide dose >0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P Conclusions RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

Cardiac resynchronization therapy-defibrillator improves long-term survival compared with cardiac resynchronization therapy-pacemaker in patients with a class IA indication for cardiac resynchronization therapy: Data from the Contak Italian Registry

Aims In candidates for cardiac resynchronization therapy (CRT), the choice between pacemaker (CRT-P) and defibrillator (CRT-D) implantation is still debated. We compared the long-term prognosis of patients who received CRT-D or CRT-P according to class IA recommendations of the European Society of Cardiology (ESC) and who were enrolled in a multicentre prospective registry. Methods and results A total of 620 heart failure patients underwent successful implantation of a CRT device and were enrolled in the Contak Italian Registry. This analysis included 266 patients who received a CRT-D and 108 who received a CRT-P according to class IA ESC indications. Their survival status was verified after a median follow-up of 55 months. During follow-up, 73 CRT-D and 44 CRT-P patients died (rate 6.6 vs. 10.4%/year; log-rank test, P = 0.020). Patients receiving CRT-P were predominantly older, female, had no history of life-threatening ventricular arrhythmias, and more frequently presented non-ischaemic aetiology of heart failure, longer QRS durations, and worse renal function. However, the only independent predictor of death from any cause was the use of CRT-P (hazard ratio, 1.97; 95% confidence interval, 1.21–3.16; P = 0.007). Conclusion The implantation of CRT-D, rather than CRT-P, may be preferable in patients presenting with current class IA ESC indications for CRT. Indeed, CRT-D resulted in greater long-term survival and was independently associated with a better prognosis

KRAS Mutations Testing in Colorectal Carcinoma Patients in Italy: From Guidelines to External Quality Assessment

BACKGROUND: Monoclonal antibodies directed against the epidermal growth factor receptor (EGFR) have been approved for the treatment of patients with metastatic colorectal carcinoma (mCRC) that do not carry KRAS mutations. Therefore, KRAS testing has become mandatory to chose the most appropriate therapy for these patients. METHODOLOGY/PRINCIPAL FINDINGS: In order to guarantee the possibility for mCRC patients to receive an high quality KRAS testing in every Italian region, the Italian Association of Medical Oncology (AIOM) and the Italian Society of Pathology and Cytopathology -Italian division of the International Academy of Pathology (SIAPEC-IAP) started a program to improve KRAS testing. AIOM and SIAPEC identified a large panel of Italian medical oncologists, pathologists and molecular biologists that outlined guidelines for KRAS testing in mCRC patients. These guidelines include specific information on the target patient population, the biological material for molecular analysis, the extraction of DNA, and the methods for the mutational analysis that are summarized in this paper. Following the publication of the guidelines, the scientific societies started an external quality assessment scheme for KRAS testing. Five CRC specimens with known KRAS mutation status were sent to the 59 centers that participated to the program. The samples were validated by three referral laboratories. The participating laboratories were allowed to use their own preferred method for DNA extraction and mutational analysis and were asked to report the results within 4 weeks. The limit to pass the quality assessment was set at 100% of true responses. In the first round, only two centers did not pass (3%). The two centers were offered to participate to a second round and both centers failed again to pass. CONCLUSIONS: The results of this first Italian quality assessment for KRAS testing suggest that KRAS mutational analysis is performed with good quality in the majority of Italian centers

The liquid biopsy in the management of colorectal cancer patients: Current applications and future scenarios

The term liquid biopsy refers to the analysis of biomarkers in any body fluid, including blood, urine and cerebrospinal fluid. In cancer, liquid biopsy testing allows the analysis of tumor-derived DNA, RNA, miRNA and proteins that can be either cell-free or contained in circulating tumor cells (CTC), extracellular vesicles (EVs) or platelets. A number of studies suggest that liquid biopsy testing could have a relevant role in the management of colorectal cancer (CRC) patients at different stages of the disease. Analysis of cell-free DNA (cfDNA), CTC and/or miRNA can provide relevant information for the early diagnosis of CRC and the identification of minimal residual disease and, more generally, the evaluation of the risk of recurrence in early CRC patients. In addition, liquid biopsy testing might allow the assessment of prognostic and predictive biomarkers in metastatic CRC patients, and the monitoring of the response to treatment and of the clonal evolution of the disease. While a number of elegant studies have shown the potential of liquid biopsy in CRC, the possibility to use this approach in the daily clinical practice is still limited. The use of non-standardized methods, the small cohorts of patients analyzed, the lack of demonstration of a clear clinical benefit are the main limitations of the studies with liquid biopsy in CRC reported up to now. The potential of this approach and the steps that need still to be taken to translate these preliminary findings in the clinic are discussed in this review

Effect of dual-chamber minimal ventricular pacing on paroxysmal atrial fibrillation incidence in myotonic dystrophy type 1 patients: A prospective, randomized, single-blind, crossover study

Background: Atrial fibrillation (AF) is a common finding in the myotonic dystrophy type 1 (DM1) population. Pacemakers (PMs) may facilitate the diagnosis and management of frequent subclinical asymptomatic AF episodes. Objective: The purpose of this study was to evaluate the effect of minimal ventricular pacing on paroxysmal AF incidence in DM1 patients during a 24-month follow-up period. Methods: We enrolled 70 DM1 patients (age 43.4 ± 13.8 years; 39 women) who underwent dual-chamber PM implantation. Patients were randomized to minimizing ventricular pacing features (ON) or not (OFF). Patients crossed over to the opposite pacing programming 12 months later. We counted the number of DM1 patients with at least 1 episode of AF, the AF total duration, and the burden recorded by PM diagnostics during the MVP ON and OFF phases. Results: Twenty-five DM1 patients (41.7%) showed at least 1 AF episode. Seven patients (11.7%) demonstrated AF episodes during MVP ON phase and 25 patients (41.7%) during MVP OFF phase (P <.001). Thirty-five patients had no AF during MVP ON or OFF phase, 3 patients had AF episodes only during MVP ON phase, 21 patients had AF episodes only during MVP OFF phase, and 4 patients had AF episodes during MVP ON and OFF phases. Activation of the MVP algorithm was associated with a 44% reduction in relative risk of developing AF. Furthermore, during the MVP ON phases, the study population showed a shorter total AF duration and a lower AF burden. Conclusion: MVP is an efficacy strategy for reducing the risk of AF in DM1 patients who have undergone PM implantation

CETP TaqIB polymorphism, serum lipid levels and risk of atrial fibrillation: A case-control study.

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoproteins (HDL) to triglyceride (TG)-rich lipoproteins. A consistent number of investigations has suggested an association between the TaqIB polymorphism of the CETP gene, plasma HDL-C levels and the risk of cardiovascular disease, but the results are controversial. The aim of this study was to determine if the TaqIB polymorphism might be related to the presence of atrial fibrillation (AF). We conducted a case-control study, enrolling 109 Caucasian unrelated patients coming from Salento (Southern Italy) with documented AF and 109 controls selected from the same ward. The CETP TaqIB genotypes were determined by RFLP-PCR. The subjects with the B2B2 genotype seem to be more susceptible to AF development (OR=2.28, 95% CI 1.06-4.89, p=0.032). The AF incidence is higher if we consider only the female subgroup (OR=5.14, 95% CI 1.57-16.82, p=0.0061). In the AF female subgroup the B2B2 patients had a statistically significant decrease of HDL-C levels (1.50 ± 0.35 vs 2.07 ± 0.42; p=0.012) and statistically higher TG levels (1.34 ± 0.46 vs 0.77 ± 0.14; p=0.027) and TG/HDL-C ratio (2.14 ± 0.80 vs 0.88 ± 0.23; p=0.007) when compared to B2B2 female control subjects. When we analyzed the linkage between the TaqIB polymorphism and the promoter variant (-629C/A), we found that 100% of the B2 alleles of the TaqIB polymorphism were associated with the A alleles of the -629 promoter polymorphism in our subjects.This study suggests that in post-menopausal women atrial fibrillation could be promoted by the association of CETP B2B2/AA genotype with higher triglycerides values

Cetuximab in first line treatment of metastatic colorectal cancer

The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC) in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS) perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER) vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI), compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to recommend cetuximab as preferred option for the first-line treatment of mCRC KRAS wild-type patients in Italy

Cetuximab in first line treatment of metastatic colorectal cancer

<p>The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC) in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS) perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER) vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI), compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to recommend cetuximab as preferred option for the first-line treatment of mCRC KRAS wild-type patients in Italy.</p