Proposal of resources optimization in the hospital treatment of heart failure by an increased utilization of cardiac rehabilitation

weight on social cost. An improved resources utilization could promote a reduction of the new hospitalization and a of medical costs. Working hypotesis: To analyze a model of increased utilization of our Cardiac Rehabilitation (CR) Unit, aiming at improving the cost/profit ratio through a better use of resources and a better assignment of care. With a reduction of average length of stay in the Operative Units for acute patients, we could promote a demand of post-acute hospitalization of 950.7 days of hospitalization that could be assigned to Cardiologic Rehabilitation Unit. Results: With the transfer of patients the utilization rate of CR would increase to 97%. With a mean period in bed of 15.3 days we could hospitalize 62 additional patients and the total margin of contribution would became positive: 69.817 euro. The break even analysis applied to costs and returns of the Unit shows a further indication to increase the hospitalization number in CR Unit with patients transfered from acute patient units. Under the same costs the recovery of efficiency leads to a reduction of variable costs. In the same time there is an increase of returns due to an increase of mean value for case and an increase of services. Conclusion: The increase in the efficiency in the utilization of CR Unit leads to an increase of the Hospital efficiency. The transfer of patients from acute units to CR Unit would allow an increased hospitalization rate for acute patients without requiring additional resources

Novel bicistronic lentiviral vectors correct β-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis.

Abstract The favorable outcome of in vivo and ex vivo gene therapy approaches in several Lysosomal Storage Diseases suggests that these treatment strategies might equally benefit GM2 gangliosidosis. Tay-Sachs and Sandhoff disease (the main forms of GM2 gangliosidosis) result from mutations in either the HEXA or HEXB genes encoding, respectively, the α- or β-subunits of the lysosomal β-Hexosaminidase enzyme. In physiological conditions, α- and β-subunits combine to generate β-Hexosaminidase A (HexA, αβ) and β-Hexosaminidase B (HexB, ββ). A major impairment to establishing in vivo or ex vivo gene therapy for GM2 gangliosidosis is the need to synthesize the α- and β-subunits at high levels and with the correct stoichiometric ratio, and to safely deliver the therapeutic products to all affected tissues/organs. Here, we report the generation and in vitro validation of novel bicistronic lentiviral vectors (LVs) encoding for both the murine and human codon optimized Hexa and Hexb genes. We show that these LVs drive the safe and coordinate expression of the α- and β-subunits, leading to supranormal levels of β-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells (HSPCs), and human SD fibroblasts. The restoration/overexpression of β-Hexosaminidase leads to the reduction of intracellular GM2 ganglioside storage in transduced and in cross-corrected SD murine neural progeny, indicating that the transgenic enzyme is secreted and functional. Importantly, bicistronic LVs safely and efficiently transduce human neurons/glia and CD34+ HSPCs, which are target and effector cells, respectively, in prospective in vivo and ex vivo GT approaches. We anticipate that these bicistronic LVs may overcome the current requirement of two vectors co-delivering the α- or β-subunits genes. Careful assessment of the safety and therapeutic potential of these bicistronic LVs in the SD murine model will pave the way to the clinical development of LV-based gene therapy for GM2 gangliosidosis

Clinical frailty scale as a predictor of outcome in elderly patients affected by moderate or severe traumatic brain injury

BackgroundOlder age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI.MethodsThis was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated.ResultsSixty patients were studied, 65% were males, their age was 76 years (IQR 70–80) and their admission GCS was 8 (IQR 6–11) with a GCS motor score of 5 (IQR 4–5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9–55.2), p < 0.0001 and 92% vs. 51% OR and 95% CI: 9.9 (2.1–46.3), p = 0.002]. In univariate analysis patients with unfavorable outcome were more frequently male and vulnerable-frail, had a higher prevalence of pre-existing neurodegenerative disease, abnormal pupil, lower GCS and had worst CT scan characteristics. At multivariate analysis, only CFS ≥ 4 and traumatic subarachnoid hemorrhage remained associated to 6-month outcome.ConclusionFrailty was associated with 6 month-outcome, suggesting that the pre-injury functional status could represent an additional indicator to stratify patient’s severity and to predict outcome

Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study

Introduction: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. Aim: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. Patients and methods: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th\ue2\u80\u9375th IQR). Results: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received \ue2\u89\ua5 3 vs \ue2\u89\ua4 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1\ue2\u80\u932 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. Conclusions: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases

Transcranial Doppler as a screening test to exclude intracranial hypertension in brain-injured patients: the IMPRESSIT-2 prospective multicenter international study

Background: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. Methods: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. Results: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%). Conclusions and relevance: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration: NCT02322970

Tre capitoli in terza rima per Borso d’Este: la Laudacio di Montagna, l’Odosophia di Sandeo e il De excellentium virorum principibus di Cornazzano

Il saggio si propone di illustrare le caratteristiche della pubblicistica encomiastica sviluppatasi nel ventennio di governo di Borso d’Este attraverso l’analisi di tre capitoli in terza rima a lui dedicati. All’interno del variegato panorama italiano la vastissima produzione encomiastica trova nella letteratura estense del periodo sue specifiche caratteristiche e finalità. Tra gli anni Cinquanta e Sessanta del XV secolo tre diversi letterati con il fine di entrare a far parte dell’entourage dell’Estense delineano progressivamente i tratti specifici della pubblicistica borsiana adottando la forma del poemetto allegorico in terza rima di stampo dantesco-petrarchesco. Il saggio analizza tali tratti nella Laudacio a Borso d’Este del veronese Leonardo Montagna, nell’Odosophia del ferrarese Ludovico Sandeo, nella redazione volgare del De excellentium virorum principibus del piacentino Antonio Cornazzano.The essay aims to illustrate the characteristics of the encomiastic poetry developed in the twenty years of government of Borso d’Este through the analysis of three chapters in terza rima dedicated to him. Within the variegated Italian panorama, the vast encomiastic production finds its specific characteristics and purposes in the Este literature of the period. Between the fifties and sixties of the fifteenth century, with the aim of becoming part of the Estense entourage, three literates progressively outlined the specific features of Borsian poetry by adopting the form of the allegorical short poem in terza rima of Dante and Petrarca style. The essay analyses these traits in the Laudacio illustrisimi principi Borsii by Leonardo Montagna from Verona, in Odosophia by Ludovico Sandeo from Ferrara and in the vernacular version of De excellentium virorum principibus by Antonio Cornazzano from Piacenza

Poesie di Francesco Gritti in dialetto veneziano

Venezia : dalla tipografia di Alvisopoli, 1815 L'incisione sottoscritta da Angelo Rizzi e Della Valle Segn.: [1]/8 2-15/8 1 v. http://catalogo.unipd.it/F?func=find-c&ccl_term=IDN=LO1E012166&local_base=SBP0

Poesie di Francesco Gritti in dialetto veneziano

Venezia : dalla tipografia di Alvisopoli, 1815 L'incisione sottoscritta da Angelo Rizzi e Della Valle Segn.: [1]/8 2-15/8 1 v. http://catalogo.unipd.it/F?func=find-c&ccl_term=IDN=LO1E012166&local_base=SBP0