Heart failure in Eastern Veneto: prevalence, hospitalization rate, adherence to guidelines and social costs

Heart failure is a preminent problem of public health, requiring innovating methods of health services organization. Nevertheless, data are still not available on prevalence, hospitalization rate, adherence to Guidelines and social costs in the general Italian population. The necessity to identifying patients with heart failure derives from the efficacy of new therapeutic interventions in reducing morbidity and mortality. In this study we aimed to identify, in a subset of the Eastern Veneto population, patients with heart failure through a pharmacologic-epidemiologic survey. The study was divided in 5 phases: 1) identification of patients on furosemide in the year 2000 in the ASL 10 of Eastern Veneto general population, through an analysis of a specific pharmaceutic service database; 2) definition of the actual prevalence of heart failure in a casual sample of these patients, through data base belonging to general practitioners, cardiologists, or others. Diagnosis was based on the following criteria: a) previous diagnosis of heart failure; b) previous hospitalization for heart failure; c) clinical evidence, with echocardiographic control in unclear cases; 3) survey of hospitalizations; 4) evaluation of adhesion to guidelines, through both databases and questionnaires; 5) analysis of the social costs of the disease, with a retrospective “bottom up” approach. From a total population of 198.000 subjects, we identyfied 4502 patients on furosemide. In a casual sample of 10.661 subjects we defined a prevalence of heart failure in Eastern Veneto of 1.1%, that rised to 7.1% in octuagenarians. The prescription of life saving drugs was satisfactory, while rather poor was the indication to echocardiography and to cardiologic consultation. Hospitalization rate for DRG 127 was low: 2.1/1000 inhabitants/year in the general polulation and 12.5 /1000 inhabitants/year in patients >70 years of age. Yearly mortality was 10.3%. Social costs were elevated (15.394 €/patient/year), due to a relevant sanitary component (hospital 53%, drugs 28%) and particularly a to an indirect cost component. In conclusion, the assumption of furosemide lends itself as a good marker for identifying patients with heart failure. Patient identification is simple, cheap and cost-efficient, and can be easily reproduced in other regional areas

DIMENSIONE OTTIMALE DEGLI ENTI LOCALI E RISPARMI DI SPESA PUBBLICA

L’avvio della fase di consolidamento fiscale iniziata nel maggio 2010 come conseguenza dello scoppio della crisi dei debiti sovrani nell’Eurozona ha riacceso i riflettori del dibattito politico-economico sugli aggregati di finanza pubblica sui quali l’Italia ha assunto obblighi normativi. I lavori presentati in questo numero sono di rilevante importanza nel dibattito attualmente in corso in Italia sulla ridefinizione dei compiti da assegnare agli enti del territorio. In particolare si pone l’attenzione su come le leggi che prevedono ed incentivano la gestione delle funzioni di spesa in forma associata siano molto importanti per un’opportuna riallocazione delle funzioni comunali e provinciali. Queste, se ben attuate, possono creare spazi per risparmi di spesa dovuti sia alla riorganizzazione gestionale, sia all’applicazione di appropriate misure dei fabbisogni standard nella quantificazione dei trasferimenti verticali

Detection of clustered circulating tumour cells in early breast cancer

Circulating tumour cell (CTC) clusters have been proposed to be major players in the metastatic spread of breast cancer, particularly during advanced disease stages. Yet, it is unclear whether or not they manifest in early breast cancer, as their occurrence in patients with metastasis-free primary disease has not been thoroughly evaluated. In this study, exploiting nanostructured titanium oxide-coated slides for shear-free CTC identification, we detect clustered CTCs in the curative setting of multiple patients with early breast cancer prior to surgical treatment, highlighting their presence already at early disease stages. These results spotlight an important aspect of metastasis biology and the possibility to intervene with anti-cluster therapeutics already during the early manifestation of breast cancer.ISSN:0007-0920ISSN:1532-182

Detection of clustered circulating tumour cells in early breast cancer

Circulating tumour cell (CTC) clusters have been proposed to be major players in the metastatic spread of breast cancer, particularly during advanced disease stages. Yet, it is unclear whether or not they manifest in early breast cancer, as their occurrence in patients with metastasis-free primary disease has not been thoroughly evaluated. In this study, exploiting nanostructured titanium oxide-coated slides for shear-free CTC identification, we detect clustered CTCs in the curative setting of multiple patients with early breast cancer prior to surgical treatment, highlighting their presence already at early disease stages. These results spotlight an important aspect of metastasis biology and the possibility to intervene with anti-cluster therapeutics already during the early manifestation of breast cancer

Clinical outcomes of volume of disease on patients receiving enzalutamide abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer

Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients. Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA versus Enza for mCRPC. Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints. Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1–62.2 months] versus AA (51.6 months; 95% CI, 42.6–60.6 months; p  = 0.003). Consistently, those with LV receiving Enza showed increased rPFS (40.3 months; 95 CI, 25.0–55.7 months) than those having AA (22.0 months; 95% CI, 18.1–26.0 months; p  = 0.004). No significant difference in OS or rPFS was observed in those with HV treated with AA versus Enza ( p  = 0.51 and p  = 0.73, respectively). In multivariate analysis of patients with LV, treatment with Enza was independently associated with better prognosis than AA. Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC

Autoimmune Lymphoproliferative Syndrome (ALPS) Disease and ALPS Phenotype: Are They Two Distinct Entities?

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte homeostasis classically due to mutation of FAS, FASL, and CASP10 genes (ALPS-FAS/CASP10). Despite recent progress, about one-third of ALPS patients does not carry classical mutations and still remains gene orphan (ALPS-U, undetermined genetic defects). The aims of the present study were to compare the clinical and immunological features of ALPS-FAS/CASP10 versus those of ALPS-U affected subjects and to deepen the genetic characteristics of this latter group. Demographical, anamnestic, biochemical data were retrieved from medical record of 46 ALPS subjects. An enlarged panel of genes (next-generation sequencing) was applied to the ALPS-U group. ALPS-U subjects showed a more complex phenotype if compared to ALPS-FAS/CASP10 group, characterized by multiorgan involvement (P = 0.001) and positivity of autoimmune markers (P = 0.02). Multilineage cytopenia was present in both groups without differences with the exception of lymphocytopenia and autoimmune neutropenia that were more frequent in ALPS-U than in the ALPS-FAS/CASP10 group (P = 0.01 and P = 0.04). First- and second-line treatments were able to control the symptoms in 100% of the ALPS-FAS/CASP10 patients, while 63% of ALPS-U needed >2 lines of treatment and remission in some cases was obtained only after target therapy. In the ALPS-U group, we found in 14 of 28 (50%) patients 19 variants; of these, 4 of 19 (21%) were known as pathogenic and 8 of 19 (42%) as likely pathogenic. A characteristic flow cytometry panel including CD3CD4-CD8-+TCRαβ+, CD3+CD25+/CD3HLADR+, TCR αβ+ B220+, and CD19+CD27+ identified the ALPS-FAS/CASP10 group. ALPS-U seems to represent a distinct entity from ALPS-FAS/CASP10; this is relevant for management and tailored treatments whenever available

Enhancement of the uptake and cytotoxic activity of doxorubicin in cancer cells by novel cRGD-semipeptide-anchoring liposomes

Novel liposemipeptides hanging cyclic azabicycloalkane-RGD or aminoproline-RGD terminals were synthesized and incorporated into liposomal nanoparticles cAba/cAmpRGD-LNP5 3C/3D. Liposomes with similar composition and lacking semipeptide conjugates were constructed for comparison (LNP, 3A), and physical encapsulation of the anticancer doxorubicin drug in both targeted and untargeted liposomes was accomplished. Microstructural analysis performed by dynamic light scattering (DLS), small-angle neutron scattering (SANS), and electron paramagnetic resonance (EPR) revealed that the conjugated nanoparticles presented an average size of 80 nm and were constituted by 5 nm thick unilamellar liposome bilayer. Flow cytometry and fluorescent microscopy studies showed that 3C-DOXO and 3D-DOXO efficiently delivered the drug into the nuclei of both quiescent and proliferating cells even in a high serum concentration environment. The uptake of doxorubicin when carried by liposomes was faster than that of the free drug, and 30 min incubation was sufficient to load cell nuclei with doxorubicin. Targeted liposomes significantly induced cell death of human breast adenocarcinoma MCF7 cells (IC50 = 144 nM, 3C-DOXO; IC50 = 274 nM, 3D-DOXO), about 2- to 6-fold more potent than free doxorubicin or 3A-DOXO controls (IC50 = 527 and 854 nM, respectively). These results suggest that cAba/cAmpRGD liposomal nanoparticles hold promise for the rapid and efficient delivery of chemotherapeutic agents to αVβ3-expressing tumor cells

Narrative medicine educational project to improve the care of patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of pulmonary function. Often patients do not adhere to inhaled therapies and this leads clinicians to switch treatments in order to improve control of the symptoms. Narrative medicine is a useful approach that helps healthcare professionals to think over the doctor–patient relationship and how patients live with their disease. The aim of this training project was to teach pulmonologists the basics of narrative medicine: to carefully listen to patients and to practice reflective writing in their relationship with them. Training on narrative medicine and parallel charts was provided through a webinar and a weekly newsletter. Across 362 narratives, written by 74 Italian pulmonologists, 92% of patients had activity limitations at their first visit. The main factor influencing the effectiveness and adherence to therapy was a positive doctor–patient relationship; indeed, if such relationship is difficult, only 21% of patients are able to resume all their activities. After learning the narrative approach, clinicians became aware of the need to spend more time listening to patients, to reflect through writing and to understand more deeply the motivations that lead people towards adherence to new therapies