L'area critica di Medicina Interna

L'evoluzione organizzativo-funzionale della Medicina Interna: l'Area Critica di terapia semintensiva - valore innovativo e missionF. Ventrella, S. Ventrella, A. Greco Emogasanalisi ed ossigenoterapia controllata in Area Critica di Medicina InternaM. Pipino, A. Paglia, R.F.P. Bufo, A. Mascolo Edema polmonare acuto e CPAPC. Tieri, C. Di Gennaro, F. Ventrella La ventilazione non invasiva in Area Critica di Medicina InternaS. Cicco, L. Iamele, F. Ventrella Il monitoraggio multiparametrico in Area Critica di Medicina InternaA. Greco, A. Castrovilli, R. Gargano, F. Ventrella Ecografia bed-side in Area Critica di Medicina InternaS. Cappello, M. Micati Protocolli di trattamento dell'iperglicemia nel paziente ospedalizzato criticoM. Errico, G.P. Sorice Alterazioni dell'acqua e del sodio nei pazienti criticiA. Belfiore, C. Stasi, C. Appice, X. Mersini Le alterazioni della potassiemia nel paziente critico di Medicina InternaM. Graziuso L'ictus ischemico: inquadramento e selezione per la trombolisi. Gestione delle gravi complicanze acute: coma, crisi ipertensiva, iperpiressia, turbe della deglutizione, convulsioniC. Coppola, B. Farneti, F. Girolamo, G. Rinaldi, F. Ventrella Lo shock in Area Critica di Medicina InternaM. Dagostino, A. Greco L'embolia polmonare in Area Critica di Medicina InternaF. Mastroianni, F. Ventrell

Risk factors for incident depression in patients at first acute coronary syndrome

The association between depression and acute coronary syndrome (ACS) is well-established and the first seems to impact meaningfully on cardiac prognosis. Nonetheless only a few studies have evaluated the relationship between incident depression, defined as new cases in patients with no history of depression, and ACS. Therefore the aim of this study is to analyse the risk factors of incident depression in a sample of patients who were presenting their first ACS. 304 consecutive patients were recruited. The presence of major (MD) and minor (md) depression was assessed with the Primary Care Evaluation of Mental Disorders (PRIME-MD), whereas its severity was evaluated with the Hospital Anxiety and Depression Scale (HADS). Evaluations were collected both at baseline and at 1, 2, 4, 6, 9 and 12 month follow ups. Out of 304 subjects (80.6% males), MD was diagnosed in 15 (4.9%) and md in 25 patients (8.2%). At baseline risk factors for a post-ACS depressive disorder were being women (MD only), widowed (md only) and having mild anhedonic depressive symptoms few days after the ACS. Clinicians should keep in mind these variables when facing a patient at his/her first ACS, given the detrimental effect of depression on cardiac prognosis

Emphysematous cystitis in an elderly male diabetic patient: a case report. A complicated urinary tract infection

Emphysematous Cystitis (EC) is a rare form of complicated urinary tract infection, characterized by the presence of gas in the bladder and in its wall. Diabetes Mellitus (DM) is the major risk factor. Clinical manifestations in EC can range from asymptomatic form to severe sepsis and fatal events. Abdominal imaging is requested to diagnose EC and evaluate its severity. Early diagnosis and appropriate management improve the outcome. We report a case of incidental EC diagnosis in an 82-yearold diabetic male who was investigated for severe anemia

High MYC Levels Favour Multifocal Carcinogenesis

The term “field cancerisation” describes the formation of tissue sub-areas highly susceptible to multifocal tumourigenesis. In the earlier stages of cancer, cells may indeed display a series of molecular alterations that allow them to proliferate faster, eventually occupying discrete tissue regions with irrelevant morphological anomalies. This behaviour recalls cell competition, a process based on a reciprocal fitness comparison: when cells with a growth advantage arise in a tissue, they are able to commit wild-type neighbours to death and to proliferate at their expense. It is known that cells expressing high MYC levels behave as super-competitors, able to kill and replace less performant adjacent cells; given MYC upregulation in most human cancers, MYC-mediated cell competition is likely to pioneer field cancerisation. Here we show that MYC overexpression in a sub-territory of the larval wing epithelium of Drosophila is sufficient to trigger a number of cellular responses specific to mammalian pre-malignant tissues. Moreover, following induction of different second mutations, high MYC-expressing epithelia were found to be susceptible to multifocal growth, a hallmark of mammalian pre-cancerous fields. In summary, our study identified an early molecular alteration implicated in field cancerisation and established a genetically amenable model which may help study the molecular basis of early carcinogenesis

A neurogenic model of adult brain cancer in Drosophila

Glioblastoma multiforme (GBM) is the most common brain cancer of the adult, with a very poor prognosis. It is characterised by a subset of undifferentiated and highly tumourigenic cells, called GBM stem cells (GSC), responsible for cancer aggressiveness and relapse. Despite the obvious anatomical differences between humans and flies, the structural and functional analogy of the respective nervous systems and the conservation of the cellular and molecular aberrations at the basis of the disease make Drosophila an excellent model for human brain cancer. Inactivation of the tumour suppressor gene PTEN is frequent in primary GBMs, resulting in the inhibition of the polarity protein Lgl1 due to aPKC hyperactivation. Dysregulation of this molecular axis is sufficient to reprogramme human neural progenitors into GSC. First, we have proved that the PTEN/aPKC/Lgl axis is conserved in Drosophila. Second, we have disrupted this conserved axis specifically in type II neuroblasts, a cell population with a lineage comparable to that of mammalian neural stem cells, obtaining aggressive tumours which persist and keep growing in the adult, leading the animals to premature death. This neurogenic model recapitulates many phenotypical traits of human brain cancers, included high proliferation rate, accumulation of undifferentiated neural cells, local invasiveness and genetic instability. With the aim to identify crucial gene expression aberrations of this devastating disease, we are going to analyse fly brain cancers by RNAseq. Following data analysis, the most relevant targets will undergo functional characterisation in patient-derived GMB cell lines showing an impairment of the PTEN/aPKC/Lgl molecular axis. The manipulated cell lines will also be injected intracranially in SCID mice to observe major changes in cancer growth and aggressiveness

A neurogenic model of adult brain cancer in Drosophila

Primary brain cancers are characterised by high cellular heterogeneity, with a subset of undifferentiated and highly tumourigenic cells responsible for cancer aggressiveness and relapse. Despite obvious anatomical differences between humans and flies, the structural and functional analogy of the respective nervous systems and the conservation of the cellular and molecular aberrations at the basis of the disease make Drosophila an excellent model for human brain cancer. Early inactivation of the tumour suppressor gene PTEN is frequent in primary glioblastoma, the most aggressive form of adult brain cancer whose origin is still controversial. This results in the inhibition of the polarity protein Lgl due to aPKC hyper-activation. Dysregulation of this molecular axis is sufficient to reprogramme human neural progenitors into cancer stem cells. After having confirmed that the PTEN/aPKC/Lgl axis is conserved in Drosophila, we have disrupted it in type II neuroblasts, a cell population with a lineage comparable to that of mammalian neural stem cells, obtaining aggressive tumours that persist and keep growing in the adult, leading the animals to premature death. This neurogenic model recapitulates many phenotypic traits of human brain cancers, included high proliferation rate, accumulation of undifferentiated neural cells and local invasiveness

Adherence to Mediterranean Diet, Malnutrition, Length of Stay and Mortality in Elderly Patients Hospitalized in Internal Medicine Wards

This investigation aimed to explore the adherence to a Mediterranean Diet and its relationship with length of stay and in-hospital mortality, circulating interleukins, body composition, and frailty, in elderly patients hospitalized in internal medicine wards. Thus, a cross-sectional study in 194 acute hospitalized, community-dwelling elderly patients was performed. Adherence to a Mediterranean Diet was evaluated by the Italian Mediterranean Index (IMI). Length of stay, but not in-hospital mortality rate, was higher in patients with a low IMI score, as compared to subjects with high IMI score. Markers of systemic inflammation, as well as circulating interleukin-6 and tumor necrosis factor alpha, were higher in patients with a low IMI score, with respect to patients with high IMI score. Furthermore, patients with low IMI score had increased fat mass and reduced lean mass, together with a higher prevalence of frailty, as compared to those presenting with high IMI score. In a multivariate logistic regression model, an IMI score < 3 resulted as an independent predictor of longer length of stay. In conclusion, low adherence to a Mediterranean Diet in elderly patients hospitalized in internal medicine wards is associated with higher length of stay and related to unfavorable changes in circulating pro-inflammatory markers and body composition

Tumour growth and tracheogenesis are separable cancer hallmarks in Drosophila

Clonal analysis is common practice in Drosophila. In particular, induction of cell clusters carrying both loss-of-function alleles of neoplastic tumour suppressors and activated forms of oncogenes has successfully been exploited to study cooperative tumourigenesis in different organs. This strategy has allowed to collect a number of morphological and molecular details on the phenotypic traits associated with cancer evolution. We previously identified Myc as a target of the Hippo pathway in Drosophila, and found out that its expression is sufficient to rescue the growth deficit of cells mutant for polarity genes, releasing their malignant potential. We also previously characterised cancer-associated tracheogenesis, a process analogue to mammalian neo-angiogenesis, as an intrinsic trait of Drosophila epithelial tumours. Here we expand on previous work, showing that tumour growth and tracheogenesis are separable traits in Drosophila epithelia. While in situ cancer expansion is mainly supported by Myc, this is not the case for migration and tracheogenesis, which mostly depend on Fos activity. These proteins are strategically found at the crossroads of the Hippo, JNK and Ras/MAPK pathways, which current literature recognises as key players in cancer progression

p53 Modulates MYC-Mediated Cell Competition in Different Cancer Contexts

Cell competition was originally described in Drosophila as a physiological process based on the comparison of relative fitness between neighbouring cells. At the end of the process, suboptimal cells, called losers, are committed to die while stimulating proliferation of the most performant cells, called winners, so maintaining tissue homeostasis. In Drosophila and mammalian development, cells showing high MYC activity behave like winners, growing at the expense of the surrounding cells which succumb by apoptosis, so unveiling a leading role for this oncoprotein in eliciting cell competition. Since MYC protein is upregulated in a large fraction of human cancers, cell competition has been speculated to play a role in human tumourigenesis. Consistently with this hypothesis, we found massive apoptotic death of stromal cells in proximity to MYC-upregulating cancer cells in a relevant number of human tumour samples, and showed that modulation of MYC activity in human cancer cell lines is sufficient to subvert their competitive drive. In Drosophila, MYC-overexpressing cells have been demonstrated to be unable to execute cell competition in a p53 loss-of-function background. With the aim to find a role for p53 in MYC-mediated cell competition, we first stained the same cancer samples as above for p53. Interestingly, the tumour regions that did not show significant signs of competitive interactions were also found negative for p53 staining, disclosing a possible function for this protein in promoting cancer-associated cell competition. Further experiments in a\uac Drosophila cancer model helped us define a dose-dependent role of p53 in MYC-overexpressing winner cells, and functional assays in co-cultures of human cancer cells confirmed that p53 function is necessary for the winner cells to execute cell competition. Altogether, our findings reveal a pro-oncogenic role of p53, that appears to cooperate with MYC in driving cell competition in different cancer contexts