Local gentamicin-collagen sponge reduces cardiovascular implantable electronic device infections and pocket hematoma.

OBJECTIVE: Implantation or replacement of a cardiovascular implantable electronic device (CIED) may be associated with complications, such as pocket hematomas and infections. This study aims to determine whether a lyophilized gentamycin-containing collagen implant (GCCI) reduces major CIED infections and pocket hematomas after implant. SUBJECTS AND METHODS: A retrospective study was conducted among patients who underwent implantation or replacement of CIED at the Tor Vergata Polyclinic (Rome, Italy) between June 2007 and November 2019. The primary combined endpoint was infection and hematoma occurrence through 12 months of follow-up post-procedure. The rate of single infectious complications, pocket hematomas or both were also assessed. RESULTS: We compared 475 patients treated with the GCCI (GCCI group) with 714 patients who did not receive it (control group). Complications occurred in 127 patients (11%); a statistically significant reduction of infections and pocket hematomas in the GCCI group was reported when compared with control patients (1% vs. 17%; p<0.0001). A total of 20 (2%) infectious events were reported, 102 (8%) patients developed a pocket hematoma, and 5 (0.4%) had both. The rate of single complications was significantly lower in GCCI group: infection 0.2% vs. 2.6% (p=0.002), pocket hematoma 0.6% vs. 13.8% (p<0.001). The association between antiplatelet/anticoagulation therapy and hematoma development was not statistically significant. CONCLUSIONS: The GCCI is a medical device that can be used in addition to local hemostasis and prophylactic doses of systemic antibiotics with the aim of reducing infective complications and pocket hematoma after permanent CIED implantation or replacement.

The evaluation of the intracavitary effusions by a bedside ultrasound examination.

OBJECTIVE: This study aims to evaluate the bedside use of the pocket-sized ultrasound (US) device for the detection of the intracavitary effusions. METHODS: We randomly enrolled 40 patients admitted to S. Andrea Hospital of Rome. Every patient received a clinical and biochemical evaluation and a bedside US examination to detect and estimate the intracavitary (pleural, pericardial and intra-abdominal) effusions; the US measurements have been compared to the computed tomography (CT) scans (as gold standard). RESULTS: The patients presented a high prevalence of effusions: right pleural 16/40 = 40% (esteemed volume 236.3±500.7 ml, mean±standard deviation m±SD), left pleural 8/40 = 20% (127.0±377.4 ml), pericardial 12/40 = 30% (47.5±72.8 ml) and intra-abdominal effusions 5/40 = 12.5% of cases (110.9±600.6 ml). Linear regression analysis showed a significant correlation between US and CT measurements: pleural r = 0.973 p <  1×10-38, pericardial r = 0.927 p <  1×10-39, intra-abdominal space r = 0.921 p <  1×10-59. The accuracy of the bedside US at the pleural, pericardial and abdominal level was respectively 98%, 93% and 96% (Cohen's kappa coefficient 0.966, 0.841 and 0.833). CONCLUSIONS: The present study showed a high prevalence of the intracavitary effusions and a high accuracy of the bedside US. The bedside US by a pocket-sized device is promising tool for its advantages of reproducibility and non-invasiveness of the device.

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study.

BACKGROUND: In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. METHODS: We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). RESULTS: In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. CONCLUSIONS: Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

Effectiveness of the new generation transcatheter aortic valve in the real life studies. Review and meta-analysis.

OBJECTIVE: The aim of the meta-analysis was to assess post-procedural outcome of the new generation of transcatheter aortic valve implantation (TAVI) devices, focusing on the transfemoral and balloon-expandable SAPIEN 3 (Edwards Lifesciences Inc., Irvine, CA, USA), the self-expanding CoreValveTM Evolut series R and PRO (R/PRO)TM (Medtronic Inc., Minneapolis, MN, USA) and ACURATE neoTM transcatheter aortic valve (Symetis SA, a Boston Scientific company, Ecublens, Switzerland). MATERIALS AND METHODS: All observational studies were retrieved through PubMed computerized database from January 2014 until June 30th, 2019. The risk difference (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. The primary end point was 30-day mortality. Safety end points included: (i) stroke, (ii) moderate/severe paravalvular leak, and (iii) the need for new permanent pacemaker implantation. RESULTS: Meta-analysis demonstrated no significant differences as regards to either 30-day mortality or stroke for all the groups of prostheses under comparison. ACURATE neo was associated with significantly less new permanent pacemaker implantation compared to SAPIEN 3 (RD: -0.06; 95% CI -0.08 to -0.03; p<0.0001; I2=0%) or to EVOLUT R/PRO (RD: -0.06; 95% CI -0.09 to -0.02; p=0.0009; I2=0%). A significant reduction of new permanent pacemaker need was observed in the group of patients implanted with SAPIEN 3 compared to EVOLUT R/PRO (RD: -0.07; 95% CI -0.09 to -0.04; p<0.00001; I2=7%). The occurrence of moderate/severe leak was significantly increased in the group of patients implanted with ACURATE neo vs. SAPIEN 3 (RD: 0.04; 95% CI 0.02 to 0.05; p<0.00001; I2=0%). No significant differences were found between ACURATE neo vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.02; p=0.69; I2=0%) and between SAPIEN 3 vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.01; p=0.28; I2=73%). CONCLUSIONS: The results of the meta-analysis show that: (1) ACURATE neo was associated with significantly less new permanent pacemaker implantation than SAPIEN 3 and EVOLUT R/PRO; (2) SAPIEN 3 had significantly lower occurrence of moderate/severe valvular leak than ACURATE neo.

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives.

Breast cancer (BC) is a complex disease with primary or acquired incurability characteristics in a significant part of patients. Immunotherapeutical agents represent an emerging option for breast cancer treatment, including the human epidermal growth factor 2 positive (HER2+) subtype. The immune system holds the ability to spontaneously implement a defensive response against HER2+ BC cells through complex mechanisms which can be exploited to modulate this response for obtaining a clinical benefit. Initial immune system modulating strategies consisted mostly in vaccine therapies, which are still being investigated and improved. However, the entrance of trastuzumab into the scenery of HER2+ BC treatment was the real game changing event, which embodied a dominant immune-mediated mechanism. More recently, the advent of the immune checkpoint inhibitors has caused a new paradigm shift for immuno-oncology, with promising initial results also for HER2+ BC. Breast cancer has been traditionally considered poorly immunogenic, being characterized by relatively low tumor mutation burden (TMB). Nevertheless, recent evidence has revealed high tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in a considerable proportion of HER2+ BC patients. This may translate into a higher potential to elicit anti-cancer response and, therefore, wider possibilities for the use and implementation of immunotherapy in this subset of BC patients. We are herein presenting and critically discussing the most representative evidence concerning immunotherapy in HER2+ BC cancer, both singularly and in combination with therapeutic agents acting throughout HER2-block, immune checkpoint inhibition and anti-cancer vaccines. The reader will be also provided with hints concerning potential future projection of the most promising immutherapeutic agents and approaches for the disease of interest.

Meta-analysis of the impact on early and late mortality of TAVI compared to surgical aortic valve replacement in high and low-intermediate surgical risk patients.

OBJECTIVE: We studied the impact of transcatheter aortic valve implantation (TAVI) compared to the surgical aortic valve replacement (SAVR) on 30-day and one-year mortality from randomized controlled trials (RCTs) in patients with severe aortic stenosis at high or low-intermediate surgical risk. MATERIALS AND METHODS: All RCTs were retrieved through PubMed computerized database and the site https://www.clinicaltrials.gov from January 2010 until March 31st, 2019. The absolute risk reduction (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. We evaluated overall mortality rates at 30-day and one-year follow-up in the comparison between TAVI vs. SAVR. We also evaluated the role played by the site access for TAVI performed through the femoral or subclavian artery (TV-TAVI) vs. SAVR, or transapically (TA-TAVI) vs. SAVR. RESULTS: In the "as-treated population" the overall 30-day mortality was significantly lower in TAVI (p=0.03) with respect to SAVR. However, the analysis for TAVI subgroups showed that 30-day mortality was (1) significantly lower in TV-TAVI vs. SAVR (p=0.006), (2) increased, not significantly, in TA-TAVI vs. SAVR (p=0.62). No significant differences were found between TAVI vs. SAVR at one-year follow-up. CONCLUSIONS: The results of our meta-analysis suggest that TV-TAVI is a powerful tool in the treatment of severe aortic stenosis at high or low-intermediate surgical risk, with a significant lower mortality with respect to SAVR. On the contrary, SAVR seems to provide better results than TA-TAVI.

Efficacy and safety of dronedarone in patients with amiodarone-induced hyperthyroidism: a clinical study.

OBJECTIVE: The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism. PATIENTS AND METHODS: We conducted a prospective study to evaluate the use of amiodarone and dronedarone in 124 patients with a history of paroxysmal atrial fibrillation who had no additional structural heart disease. All patients received amiodarone 200 mg qd. Out of 124 patients, 56 (45%) switched to dronedarone 400 mg bid due to amiodarone-induced hyperthyroidism and the remaining 68 patients (55%), with normal thyroid function, continued to receive amiodarone. The follow-up period was 12 months, and the patients were regularly monitored. RESULTS: The primary outcome after 6 months dronedarone and amiodarone group was 56 and 68, including 38 (68%) and 54 (79.4%) (Odds ratio [OR] = 1.17, 95% confidence interval [95% CI] = 0.68-2.02) patients with sinus rhythm (SR) and 18 (32.14%) and 14 (28.6%) (odds ratio [OR] = 0.64, confidence interval [95% CI] = 0.29-1.40) patients with atrial fibrillation (AF). The secondary outcome after 12 months showed significant difference in thyroid function in the dronedarone group. Out of 46 patients, 24 (56.18%) patients reduced hyperthyroidism compared to the amiodarone group; out of 68, 6 (8.9%) patients were observed to have hyperthyroidism. At 12 months, there were 24 (43%) and 22 (62%) (odds ratio [OR] = 0.75, confidence interval [95% CI] = 0.38-1.49) patients with SR, and 32 (57%) and 26 (38%) (odds ratio [OR] = 0.67, confidence interval [95% CI] = 0.36-1.25) patients with AF. CONCLUSIONS: In our study, dronedarone appears to be a good therapeutic option in the treatment of atrial fibrillation in patients with amiodarone-induced hyperthyroidism. However, long-term studies are needed to estimate the efficacy and toxicity of both drugs.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

OBJECTIVE: Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. MATERIALS AND METHODS: Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. RESULTS: Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. CONCLUSIONS: Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Portosystemic encephalopathy in an 86-year-old patient : a clinical challenge.

Abernethy malformations are rare vascular abnormalities, classified into two types : type 1 if the portal vein is absent, type 2 when the portal blood is diverted into vena cava through a hypoplastic portal vein. These conditions present symptoms related to portosystemic shunting, and usually become clinically evident in children or young adults. Here we report the first case of Abernethy malformation diagnosed in an 86-year-old female patient affected by portosystemicencephalopaty.

Laparoscopic versus robotic radical hysterectomy after neoadjuvant chemotherapy in locally advanced cervical cancer: a case control study.

OBJECTIVE: To compare the surgical outcome of robotic radical hysterectomy (RRH) versus laparoscopic radical hysterectomy (LRH) for the treatment of locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: From August 1st 2010 to July 1st 2012 a prospective data collection of women undergoing RRH for cervical cancer stage FIGO IB2 to IIB, after neoadjuvant chemotherapy, was conducted at National Cancer Institute "Regina Elena" of Rome. All patients deemed operable underwent class C1 RRH with pelvic lymphadenectomy within 4 weeks from the last chemotherapy cycle. RESULTS: A total of 25 RRH were analyzed, and compared with 25 historic LRH cases. The groups did not differ significantly in body mass index, stage, histology, number of pelvic lymph nodes removed. The median operative time was the same in the two groups with 190 min respectively. The median estimated blood loss (EBL) was statistically significant in favor of RRH group. Median length of stay was shorter, for the RRH group (4 versus 6 days, P = 0.28). There was no significant difference in terms of intraoperative and postoperative complications between groups but in the RRH group we observed a greater number of total complications compared to the control group. CONCLUSION: This study shows that RRH is safe and feasible in LACC after NACT compare to LRH. However, a comparison of oncologic outcomes and cost-benefit analysis is still needed and it has to be carefully evaluated in the future.

Non-invasive hemodynamic analysis in cardiac resynchronization therapy patients wearing quadripolar left ventricular leads: the importance of pacing electrode selection.

AIM: Quadripolar left ventricular (LV) leads offer multiple choices for LV pacing increasing programming flexibility. Aim of this study is to assess the influence of LV pacing vector selection on hemodynamic parameters for patients who underwent cardiac resynchronization therapy (CRT) using quadripolar LV lead chronically evaluated with a non-invasive approach by Nexfin(®) system provided analysis (BMEYE B.V., Amsterdam, The Netherlands). METHODS AND RESULTS: In 16 CRT patients implanted with a quadripolar LV lead (mean follow-up 8,8 ±13,4 months after implantation), we measured Cardiac Output (CO), Mean Blood Pressure (MBP), Total Peripheral Resistance (TPR), LV dP/dt max and Stroke volume (SV) from each one of the ten available bipolar pacing configurations. All the recorded parameters showed marked differences among the ten pacing configurations, but dP/dt max, SV and TPR were those showing the wider range, depending of the selected pacing vector. The average delta for the whole group of subjects between the maximum and minimum hemodynamic values for each pacing configuration were 15.9% for SV, 21.1% for dP/dt max and 20.3% for TPR. Inter-individual analysis of data failed to identify a link between a specific pacing vector and the hemodynamic response. CONCLUSION: Our study demonstrates that different bipolar pacing configurations, even if arising from a single CS branch, substantially modify the hemodynamic effect of LV pacing in CRT patients. Moreover, the non-invasive hemodynamic analysis suggests the better pacing configuration should be established individually and could represent an important issue in optimizing CRT during follow-up.

Body composition phenotype: Italian Mediterranean Diet and C677T MTHFR gene polymorphism interaction.

OBJECTIVES: Strategies to improve weight maintenance are focused on considering the genetic makeup and its interaction with dietary intake, with the aim to identify vulnerable individuals that will benefit from a variety of more personalized dietary recommendations. The aim of the study was to examine the impact of the C677T MTHFR gene Polymorphism on body composition changes induced by a balanced hypocaloric Italian Mediterannean diet (IMD). SUBJECTS AND METHODS: Participation in the study included a complete screening of anthropometry and body composition by Dual-energy X-ray absorptiometry (DXA), and a genotyping for the C677T MTHFR polymorphism. 70 Italian Caucasian obese were enrolled and 56 of them completed the screening at baseline and 12 weeks after the nutritional intervention. RESULTS: T(+) carriers had a higher content of Total Body Fat (TBFat), and Lean (TBLean), reflecting on higher weight and BMI, than T(-) carriers. After IMD, the 28.6% and 71.4% of total subjects decreased weight and TBFat (Kg), respectively. The relative changes were: delta % = -9.09±3.85 for weight; delta % = -15.79±8.51 for TBFat; delta % = -3.80±5.60 for TBLean. The 5.3% of subjects who reached the end point of intervention, and the 8.9% who reduced TBFat (%) below the cut-off of preobesity, were T(-) carriers. A loss of TBLean (Kg) was observed in the 5.1% and 23.5% of T(-) and T(+) carriers. CONCLUSIONS: MTHFR genetic variations analysis would be an innovative tool for the nutritional assessment, in order to predict the therapeutic response of obese subjects, in terms of fat and lean mass loss.

Effects of dark chocolate in a population of normal weight obese women: a pilot study.

BACKGROUND: Normal weight obese (NWO) syndrome is defined as an excessive body fat associated with a normal body mass index and characterized by a higher risk for cardiovascular morbidity and mortality. Recent studies have demonstrated that dark chocolate (DC) has beneficial effects in the prevention of cardiovascular diseases (CVD) due to its anti-inflammatory and antioxidant properties. AIM: The aim of the present study was to investigate the effects of DC consumption on lipid profile, inflammatory markers, biochemical parameters, and blood pressure, in NWO women. MATERIALS AND METHODS: 15 women affected by NWO syndrome, aged 20-40 years, were included in the study. After a DC-free washout period, subjects received DC (100 g/die) containing 70% cocoa for 7-days. Body composition by Dual energy-X-ray absorptiometry (DXA) was performed at baseline. Blood pressure, anthropometric measurements, biochemical parameters and plasma levels of some cytokines were measured before and after DC consumption. RESULTS: After DC consumption, we observed a significant increase in the HDL cholesterol level (Delta% = +10.41±13,53; p ≤ 0.05), a significant decrease of total cholesterol/HDL cholesterol ratio (Delta %= -11.45±7.03; p ≤ 0.05), LDL/HDL cholesterol ratio (Delta % = -11.70±8.91; p ≤ 0.05), and interleukin-1 receptor antagonist (IL-1Ra) (Delta % = -32.99±3.84; p ≤ 0.05). In addition, a reduction in abdomen circumference was observed. We also found a positive correlation between changes in atherogenic indices, and IL-1Ra, abdomen reduction. CONCLUSIONS: Our findings suggest that regular consumption of DC could be useful in maintaining a good atherogenic profile, due to the favourable effects on HDL cholesterol, lipoprotein ratios and inflammation markers.

A multicenter phase II randomized trial of docetaxel/gemcitabine versus docetaxel/capecitabine as first-line treatment for advanced breast cancer: a Gruppo Oncologico Italia Meridionale study.

OBJECTIVE: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. METHODS: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m(2) on day 1, gemcitabine 1,000 mg/m(2) on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m(2) on day 1, capecitabine 1,250 mg/m(2) twice daily on days 1-14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. RESULTS: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6-57.8]; arm B, 38.9% (95% CI 23-54.8). Median progression-free survival was 10.9 months (95% CI 8.1-13.7) in arm A and 10 months (95% CI 8.8-11.2) in arm B. Overall survival was 26 months (95% CI 22.0-30.0) in arm A and 28 months (95% CI 23.4-32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3-4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. CONCLUSIONS: Both regimens were active and well tolerated in advanced breast cancer.

Biological progression of breast cancer and clinical implications.

The classic view of tumor progression is that genetic mutation introduced in differentiated or progenitor cells causes tumors, through the acquisition of advantages for survival, and leading to phenotypic heterogeneity. Another theory (stem cell hypothesis) considers that tumor progression derives from cells within the tumor with stem cell characteristics of self-renewal and multiple differentiation potential. It is still unknown the timing of expression of various biological characteristics of breast cancer during the progression cascade, and the existence of clonal heterogeneity within primary tumor and synchronous or asynchronous distant metastases contributes to treatments failures.

[Specificity of action of anticancer agents]. / Specificità d'azione dei farmaci antineoplastici.

Since the first cancer chemotherapy use, efforts have been made in identifying drugs with an antitumor specific action, but cancer is a very complex situation to be cured with a single agent, and to increase drugs selective cytotoxicity new agent combinations, or innovative cellular cycle related schedule, or the use of pro-drugs have been developed. Notwithstanding some relevant improvements in results, chemotherapy remains often a palliative approach. The improved knowledge of the biology of cancer, and of molecular mechanisms and specific targets, has recently modified the approach to various tumors. In particular, the identification of a single and specific genetic alteration in some tumors such as myeloid chronic leukaemia or gastrointestinal stromal tumors (GIST) led to the development of imatinib, a "target" drug with a multikinase inhibitor activity towards the specific genetic alteration; this unique opportunity is not applicable to other tumors, because usually tumors have multiple genetic alterations with very complex molecular pathways. The development of drugs with a multitarget action is probably the best approach to the majority of human cancers, but other possibility are the combination of multiple agents, each with known selective activity towards a specific molecular target, or the choice of a chemotherapic drug in combination with one or more molecularly targeted drugs. The knowledge of the multiple and extremely complex molecular pathways of the neoplastic cells will hopefully drive oncologic science towards a more "exact" science, with the use of "personalized" treatment in each cancer patient.

Use of a comprehensive numerical model to improve biventricular pacemaker temporization in patients affected by heart failure undergoing to CRT-D therapy.

Cardiac resynchronization therapy by biventricular pacemaker/ICD implantation is a validated therapy for patients affected by heart failure with asynchrony of ventricular contraction. Considering the large number of parameters which play a role in cardiac resynchronization therapy, a comprehensive numerical model of cardiocirculatory system could be a useful tool to support clinical decisions. A variable elastance model of ventricles was updated to model the interventricular septum and to simulate the interventricular and the intraventricular desynchrony, and the effect of the biventricular stimulation. In addition, a numerical model of the biventricular pacemaker, which drives the beginning of the heart chambers and interventricular septum contraction, was also developed. In order to validate the model, five patients affected by dilated cardiomyopathy were analysed by echocardiography and electrocardiography before implantation, 24 h and 3 months after the implantation. The developed numerical model permits to reproduce clinical data and to estimate the trend of parameters that are difficult to measure (i.e. left ventricular systolic elastance). Furthermore, the model permits to study the effect of different biventricular pacemaker temporizations on hemodynamic variables.

[Psyche and cancer]. / Psiche e cancro.

Although the relationship between psyche and cancer dates back many centuries, and several studies were conducted on this topic during the last decades, the role of psychological factors in the development of cancer is still controversial. Although a lot of factors have been considered, attention has been focused mainly on stress, which has been evaluated also in experimental models. Generally, the results of case-control studies have been contradictory, and at times more stressfull events have been recorded in patients with benign tumors than in those with cancer. On the contrary, a higher incidence of stress-related cancers has not been documented in cohort studies. Since cancer is a genetic disease, it is difficult to hypothesize that psychological factors may permanently alter nucleotide sequence giving rise to multiple mutations needed for cancer development. At present, there is no sufficient evidence to affirm that psychological factors may contribute without doubt to cancer development.

Recent advances in the adjuvant treatment of early breast cancer.

The majority of breast cancers are actually diagnosed at an early stage. Selection of the best treatment in the adjuvant setting represents a paramount step to reduce the risk of recurrence and cancer-specific mortality. At the present time decision making is based on individualized risk assessment, that takes into account patient and tumor clinical-pathological characteristics. New available tools, such as gene expression profiling, offer the potential to provide accurate prognostic and predictive information, but they require further validation. The present article provides an overview of current strategies in adjuvant breast cancer setting, and addresses a number of unresolved questions related to the role of taxanes, trastuzumab and hormonal treatment.