Clinical Characteristics and Course of Patients Entering Cardiac Rehabilitation with Chronic Kidney Disease: Data from the Italian Survey on Cardiac Rehabilitation

This survey shows the clinical risk profile, resource utilization, pharmacologic treatment, and course of cardiac rehabilitation (CR) programs in patients with chronic kidney disease (CKD). Data from 165 CR units in Italy were collected online from January 28 to February 10, 2008. The study cohort consisted of 2281 patients: 200 CKD patients and 2081 non-CKD patients. CKD patients were older and showed more comorbidity and complications during CR, a more complex clinical course and interventions with less functional evaluation, and a different pattern of drug therapy at hospital discharge. CKD patients had higher mortality during CR programs due to heart failure, respiratory insufficiency, and cognitive impairment. These findings suggest that patients with CKD should not be denied access to CR, provided careful attention to clinical status, possible complications, optimization of drug therapy, and close followup

Clinical Characteristics and Course of Patients Entering Cardiac Rehabilitation with Chronic Kidney Disease: Data from the Italian Survey on Cardiac Rehabilitation

This survey shows the clinical risk profile, resource utilization, pharmacologic treatment, and course of cardiac rehabilitation (CR) programs in patients with chronic kidney disease (CKD). Data from 165 CR units in Italy were collected online from January 28 to February 10, 2008. The study cohort consisted of 2281 patients: 200 CKD patients and 2081 non-CKD patients. CKD patients were older and showed more comorbidity and complications during CR, a more complex clinical course and interventions with less functional evaluation, and a different pattern of drug therapy at hospital discharge. CKD patients had higher mortality during CR programs due to heart failure, respiratory insufficiency, and cognitive impairment. These findings suggest that patients with CKD should not be denied access to CR, provided careful attention to clinical status, possible complications, optimization of drug therapy, and close followup

Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. Conclusion: The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue

Erratum to: Respiratory diphtheria due to Corynebacterium ulcerans transmitted by a companion dog, Italy 2014

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delta C-13 signatures of organic aerosols:Measurement method evaluation and application in a source study

Analysis of the stable carbon isotope 13C in organic carbon (OC) can give insight into sources and atmospheric processing of carbonaceous aerosols, provided the 13C source signatures are known. However, only few data on 13C signatures of OC emitted by common sources of carbonaceous aerosol are available in Europe. We present and evaluate an improved version of a measurement method to obtain δ13C signatures on organic aerosols desorbed from filter samples at three different desorption temperatures (200 °C, 350 °C and 650 °C) and apply it in a source study. With our calibration approach, the reproducibility of a L-Valine reference material desorbed at a single temperature step of 650 °C shows a standard deviation of 0.19‰ over a period of more than one year. The average δ13C value for this reference material over 248 measurements is −24.10‰, which shows only a slight bias to the nominal value of −24.03‰. Repeated analysis of ambient filter samples desorbed at three temperature steps show typical standard deviations of about 0.3‰ for all temperature steps (200 °C, 350 °C and 650 °C). Isotopic fractionation due to partial thermal desorption during the individual temperature steps was tested on single compound reference materials. It showed significant isotopic fractionation only at temperature steps, in which a very minor fraction of the compound was desorbed. Possible isotope effects caused by charring of organic material were investigated and found to be not significant. The thermal desorption method was applied to various source filter samples from the region of Naples, Italy. We analyzed two different biomass burning sources, exhaust from a city bus and traffic emissions collected in a tunnel and compared these to ambient filter samples from the same region. δ13C signatures of the total OC show values in a narrow range of about −28‰ to −26‰ for all sources, which does not allow a source apportionment only based on 13C. Nevertheless, the results add information to a source inventory of δ13C, where information of 13C in organic aerosol from specific emission sources are rare. City bus emissions show little variation of δ13C over the temperature steps, whereas biomass burning aerosol is enriched in 13C for OC desorbed at 650 °C. For PM10 samples in the urban tunnel an enrichment in δ13C at the 650 °C temperature steps was observed, which is likely caused by the contribution of carbonate carbon to the carbonaceous material desorbed at this temperature step

Ranolazine attenuates trastuzumab-induced heart dysfunction by modulating ROS production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Burden of Respiratory Syncytial Virus in the European Union:estimation of RSV-associated hospitalizations in children under 5 years

Background No overall estimate of respiratory syncytial virus (RSV)-associated hospitalizations in children aged under 5 years has been published for the European Union (EU). We aimed to estimate the RSV hospitalization burden in children aged under 5 years in EU countries and Norway, by age group. Methods We collated national RSV-associated hospitalization estimates calculated using linear regression models via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands, and Scotland, 2006-2018. Additional estimates were obtained from a systematic review. Using multiple imputation and nearest neighbor matching methods, we estimated overall RSV-associated hospitalizations and rates in the EU. Results Additional estimates for 2 countries (France and Spain) were found in the literature. In the EU, an average of 245 244 (95% confidence interval [CI], 224 688-265 799) yearly hospital admissions with a respiratory infection per year were associated with RSV in children aged under 5 years, with most cases occurring among children aged under 1 year (75%). Infants aged under 2 months represented the most affected group (71.6 per 1000 children; 95% CI, 66.6-76.6). Conclusions Our findings will help support decisions regarding prevention efforts and represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunization programs in Europe.The study estimated that an average of 245 244 children aged under 5 years are hospitalized annually due to RSV in the EU, with the highest hospitalization rates in children aged less than 2 months (71.6 per 1000 children)

Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers

Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection