Non-urgent patients in the Emergency Departement

The non-urgent patients in the Emergency Departement (ED) are a widespread challenging problem. In the present study we investigated the relationship between the non-urgent patients in ED and the primary care services in an urban area (Mestre- Venezia). An alternative management of these patients supported by a group of family doctors in a separate laboratory, close to the ED, and using the ED triage system, has also been studied. The management of these patients in terms of waiting time, percent of patients who have left the ED without being seen and inappropriate dismissions, was sactisfactory. Otherwise 50% of the patients were sent to an urgent specialistic advisory in spite of their non-urgent problem presented. The involvement of primary care providers and a reasonable limit to an unjustified specialistic advisory are requiered to achieve a reliable alternative management for non-urgent patients in ED

Tp53 deletion in B lineage cells predisposes mice to lymphomas with oncogenic translocations

Inactivating Tp53 mutations are frequent genetic lesions in human tumors that harbor genomic instability, including B lineage lymphomas with IG translocations. Antigen receptor genes are assembled and modified in developing lymphocytes by RAG/AID-initiated genomic rearrangements that involve the induction of DNA double strand breaks (DSBs). Although TP53 inhibits the persistence of DSBs and induces apoptosis to protect cells from genomic instability and transformation, the development of spontaneous tumors harboring clonal translocations has not been reported in mice that only lack wild-type Tp53 protein or express Tp53 mutants. Tp53-deficient (Tp53-/-) mice succumb to T lineage lymphomas lacking clonal translocations but develop B lymphoid tumors containing immunoglobulin (Ig) translocations upon combined inactivation of DSB repair factors, RAG mutation or AID overexpression; mice expressing apoptosis-defective Tp53 mutants develop B cell lymphomas that have not been characterized for potential genomic instability. As somatic rather than germline inactivating mutations of TP53 are typically associated with human cancers and Tp53 deletion has cellular context dependent effects upon lymphocyte transformation, we generated mice with conditional Tp53 deletion in lineage-committed B lymphocytes to avoid complications associated with defective Tp53 responses during embryogenesis and/or in multi-lineage potential cells and, thereby, directly evaluate the potential physiological role of Tp53 in suppressing translocations in differentiated cells. These mb1-cre:Tp53flox/flox mice succumbed to lymphoid tumors containing Ig gene rearrangements and immuno-phenotypes characteristic of B cells from various developmental stages. Most mb1-cre:Tp53flox/flox tumors harbored clonal translocations, including Igh/c-myc or other oncogenic translocations generated by the aberrant repair of RAG/AID-generated DSBs. Our data indicate that Tp53 serves critical functions in B lineage lymphocytes to prevent transformation caused by translocations in cell populations experiencing physiological levels of RAG/AID-initiated DSB intermediates, and provide evidence that the somatic TP53 mutations found in diffuse large B-cell lymphoma and Burkitt's lymphoma may contribute to the development of these human malignancies

Home telemonitoring for patients with acute exacerbation of chronic obstructive pulmonary disease: A randomized controlled trial

BACKGROUND: Although a number of studies have suggested that the use of Telemonitoring (TM) in patients with Chronic Obstructive Pulmonary Disease (COPD) can be useful and efficacious, its real utility in detecting Acute Exacerbation (AE) signaling the need for prompt treatment is not entirely clear. The current study aimed to investigate the benefits of a TM system in managing AE in advanced-stage COPD patients to improve their Health-Related Quality of Life (HRQL) and to reduce utilization of healthcare services. METHODS: A 12-month Randomised Controlled Trial (RCT) was conducted in the Veneto region (Italy). Adult patients diagnosed with Class III-IV COPD in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification were recruited and provided a TM system to alert the clinical staff via a trained operator whenever variations in respiratory parameters fell beyond the individual's normal range. The study's primary endpoint was HRQL, measured by the Italian version of the two Short Form 36-item Health Survey (SF36v2). Its secondary endpoints were: scores on the Hospital Anxiety and Depression Scale (HADS); the number and duration of hospitalizations; the number of readmissions; the number of appointments with a pulmonary specialist; the number of visits to the emergency department; and the number of deaths. RESULTS: Three hundred thirty-four patients were enrolled and randomized into two groups for a 1 year period. At its conclusion, changes in the SF36 Physical and Mental Component Summary scores did not significantly differ between the TM and control groups [(-2.07 (8.98) vs -1.91 (7.75); p\u2009=\u20090.889 and -1.08 (11.30) vs -1.92 (10.92); p\u2009=\u20090.5754, respectively]. Variations in HADS were not significantly different between the two groups [0.85 (3.68) vs 0.62 (3.6); p\u2009=\u20090.65 and 0.50 (4.3) vs 0.72 (4.5); p\u2009=\u20090.71]. The hospitalization rate for AECOPD and/or for any cause was not significantly different in the two groups [IRR\u2009=\u20090.89 (95% CI 0.79-1,04); p\u2009=\u20090.16 and IRR\u2009=\u20090.91 (95% CI 0,75 - 1.04); p\u2009=\u20090.16, respectively]. The readmission rate for AECOPD and/or any cause was, however, significantly lower in the TM group with respect to the control one [IRR\u2009=\u20090.43 (95% CI 0.19-0.98); p\u2009=\u20090.01 and 0.46 (95% CI 0.24-0.89); p\u2009=\u20090.01, respectively]. CONCLUSION: Study results showed that in areas where medical services are well established, TM does not significantly improve HRQL in patients with COPD who develop AE. Although not effective in reducing hospitalizations, TM can nevertheless facilitate continuity of care during hospital-to-home transition by reducing the need for early readmission

The Molecular Scaffold Kinase Suppressor of Ras 1 Is a Modifier of Ras(V12)-Induced and Replicative Senescence

In primary mouse embryo fibroblasts (MEFs), oncogenic Ras induces growth arrest via Raf/MEK/extracellular signal-regulated kinase (ERK)-mediated activation of the p19(ARF)/p53 and INK4/Rb tumor suppressor pathways. Ablation of these same pathways causes spontaneous immortalization in MEFs, and oncogenic transformation by Ras requires ablation of one or both of these pathways. We show that Kinase Suppressor of Ras 1 (KSR1), a molecular scaffold for the Raf/MEK/ERK cascade, is necessary for Ras(V12)-induced senescence, and its disruption enhances primary MEF immortalization. Ras(V12) failed to induce p53, p19(ARF), p16(INK4a), and p15(INK4b) expression in KSR1(−/−) MEFs and increased proliferation instead of causing growth arrest. Reintroduction of wild-type KSR1, but not a mutated KSR1 construct unable to bind activated ERK, rescued Ras(V12)-induced senescence. On continuous culture, deletion of KSR1 accelerated the establishment of spontaneously immortalized cultures and increased the proportion of cultures escaping replicative crisis. Despite enhancing escape from both Ras(V12)-induced and replicative senescence, however, both primary and immortalized KSR1(−/−) MEFs are completely resistant to Ras(V12)-induced transformation. These data show that escape from senescence is not necessarily a precursor for oncogenic transformation. Furthermore, these data indicate that KSR1 is a member of a unique class of proteins whose deletion blocks both senescence and transformation

Performance assessment across different care settings of a heart failure hospitalisation risk-score for type 2 diabetes using administrative claims

Predicting the risk of cardiovascular complications, in particular heart failure hospitalisation (HHF), can improve the management of type 2 diabetes (T2D). Most predictive models proposed so far rely on clinical data not available at the higher Institutional level. Therefore, it is of interest to assess the risk of HHF in people with T2D using administrative claims data only, which are more easily obtainable and could allow public health systems to identify high-risk individuals. In this paper, the administrative claims of > 175,000 patients with T2D were used to develop a new risk score for HHF based on Cox regression. Internal validation on the administrative data cohort yielded satisfactory results in terms of discrimination (max AUROC = 0.792, C-index = 0.786) and calibration (Hosmer-Lemeshow test p value < 0.05). The risk score was then tested on data gathered from two independent centers (one diabetes outpatient clinic and one primary care network) to demonstrate its applicability to different care settings in the medium-long term. Thanks to the large size and broad demographics of the administrative dataset used for training, the proposed model was able to predict HHF without significant performance loss concerning bespoke models developed within each setting using more informative, but harder-to-acquire clinical variables