A Mouse Model of Pulmonary Metastasis from Spontaneous Osteosarcoma Monitored In Vivo by Luciferase Imaging

BACKGROUND: Osteosarcoma (OSA) is lethal when metastatic after chemotherapy and/or surgical treatment. Thus animal models are necessary to study the OSA metastatic spread and to validate novel therapies able to control the systemic disease. We report the development of a syngeneic (Balb/c) murine OSA model, using a cell line derived from a spontaneous murine tumor. METHODOLOGY: The tumorigenic and metastatic ability of OSA cell lines were assayed after orthotopic injection in mice distal femur. Expression profiling was carried out to characterize the parental and metastatic cell lines. Cells from metastases were propagated and engineered to express Luciferase, in order to follow metastases in vivo. PRINCIPAL FINDINGS: Luciferase bioluminescence allowed to monitor the primary tumor growth and revealed the appearance of spontaneous pulmonary metastases. In vivo assays showed that metastasis is a stable property of metastatic OSA cell lines after both propagation in culture and luciferase trasduction. When compared to parental cell line, both unmodified and genetically marked metastatic cells, showed comparable and stable differential expression of the enpp4, pfn2 and prkcd genes, already associated to the metastatic phenotype in human cancer. CONCLUSIONS: This OSA animal model faithfully recapitulates some of the most important features of the human malignancy, such as lung metastatization. Moreover, the non-invasive imaging allows monitoring the tumor progression in living mice. A great asset of this model is the metastatic phenotype, which is a stable property, not modifiable after genetic manipulation

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Evaluation of bedload yield in two small sand-bed rivers of the Ravenna province (Italy)

Sediment transport, and bedload transport in particular, is one of the most dynamic and complex hydraulic and geomorphologic processes in a river basin. Sediment supply is strictly dependent on erosion processes in the catchment which are highly controlled by primary factors such as: climate, basin area, geology and topography. Sediment transport influences the geomorphic responses of rivers and the equilibrium of the fluvial environment. The sampling devices and techniques used in the field to quantify bedload transport are very few. Difficulties liked to their efficiency, together with the request of large human and financial resources, have proven that bedload transport is one of the most difficult fluvial processes to measure. These difficulties have pushed scientists to develop physically based and empirical formulas to quantify bedload transport based on both laboratory and field studies. However, field measurements are very limited. Despite continued efforts, bedload transport equations still have limited application. Thus, understanding and quantifying sediment yield is becoming increasingly the center of attention of a variety of scientific and societal problems. Given the poor knowledge of river supplies at regional scale, this research aims at quantifying the bedload yield to the Romagna beaches through field investigations and measurements on two representative rivers to enlarge the actual dataset. By means of hydraulic and hydrological approach and, most of all, by means of bed load transport direct measurement campaigns in the field, this research aims at defining the quantity of sediment flux of the Fiumi Uniti and Savio rivers. They both flow from the northern Apennines to the Padan plain and outflow into the Adriatic Sea in the Ravenna province. Focusing particularly on bedload transport, the investigation took place in the last 10 kilometers of the rivers, i.e. in the vicinity of their mouths. Field campaigns have been carried out by means of the Helley-Smith bedload sampler. Field measurements started in 2005-06 by previous authors were revise and were integrated by the author in 2019. Repeated samplings carried out during different flood conditions have permitted to calculate bedload rating curves (and annual bedload yields). Bathymetric surveys carried out on the river downstream reaches, revealed the presence of bedforms. Since these play an important role in the interaction between flow and sediment transport, further investigation have been done on their role in controlling bedload. Important components affecting the bedload transport rates and its calculation using the classical bedload equations were also investigated. They include the threshold conditions of incipient bedload motion and the roughness component of dune bedforms. The field data indicate that bedload sediment yield to the Romagna beaches is highly variable and that the Fiumi Uniti bedload transport is higher than that of the Savio river. Finally, a comparison of the field data with the results of well-known criteria to predict bedload transport rate has been performed to define the best equation to be used at regional scale to quantify bedload supply to beaches in a mid-term scenario.Il trasporto di sedimenti, e in particolare il trasporto solido (al fondo), è uno dei più dinamici e complessi risultati dei processi idro-climatici, idraulici e geomorfologici che si verificano all’interno di un bacino fluviale. La capacità di produzione sedimentaria dipende strettamente dalla fornitura di sedimenti dal bacino che è altamente controllata da fattori primari quali: clima, area del bacino, geologia e topografia. Ulteriormente influenzato da impatti antropici, il trasporto di sedimenti controlla le risposte geomorfiche dei fiumi che, a loro volta possono essere ulteriormente esacerbati dai cambiamenti climatici. Diversi sono gli strumenti e le tecniche di campionamento utilizzati sul campo per quantificare il trasporto solido. Le difficoltà connesse alla loro efficienza, assieme alla richiesta di grandi risorse umane e finanziarie, hanno dimostrato che il trasporto solido è uno dei processi fluviali più difficili da misurare. Negli ultimi cinquant'anni tali difficoltà hanno spinto gli scienziati a sviluppare modelli empirici per la stima del trasporto solido al fondo. Sono state proposte diverse formule basate fondamentalmente su studi di laboratorio e di campo, pur considerando che le misure dirette di campo sono molto limitate. Nonostante i continui sforzi compiuti, esistono ancora grandi limiti delle equazioni. Comprendere e quantificare il tasso dei sedimenti trasportati sta diventando sempre più importante per una varietà di problemi sia da un punto di vista scientifico che applicativo. Sebbene vi siano alcuni sporadici studi sperimentali sugli apporti solidi fluviali in regione Emilia-Romagna, i dati a disposizione sono estremamente esigui e, sfortunatamente, si riferiscono solo a un numero limitato di fiumi. Data la scarsa conoscenza degli apporti fluviali a scala regionale, questa ricerca mira a quantificare il trasporto solidi dei corsi d’acqua attraverso indagini sul campo e misurazioni dirette svolte su due fiumi rappresentativi con lo scopo di ampliare il dataset attuale a disposizione. Mediante un approccio di tipo idraulico ed idrologico e, soprattutto, mediante campagne di misura diretta del trasporto solido, si è quantificato il trasporto al fondo nei Fiumi Uniti e Savio. Entrambi i fiumi scorrono dall'Appennino settentrionale alla Pianura Padana, sfociando nel mare Adriatico in prossimità della provincia di Ravenna. Concentrandosi in particolare sul trasporto solido fluviale, l'indagine si svolge nei pressi degli ultimi dieci chilometri dei corsi d’acqua, a ridosso delle zone fociali. Le campagne sono state condotte con un approccio di misurazione diretta ( ossia tramite l’utilizzo del campionatore Helley-Smith) iniziato nel 2005-06 da autori precedenti ed esteso dall’autrice nel 2019. Campionamenti ripetuti effettuati in diverse condizioni di piena hanno permesso di calcolare le scale di deflusso degli apporti solidi (e il carico solido al fondo fluviale annuale). Ulteriori indagini batimetriche sono state condotte in prossimità delle sezioni di misura, rivelando la presenza di forme di fondo. Ulteriori approfondimenti sono stati svolti relativamente ai fattori che influenzano il trasporto solido, del quale è stata anche effettuata una stima analizzando alcune classiche equazioni presenti in letteratura. Sono state infatti considerate sia le condizioni di soglia del movimento dei sedimenti sia la componente di rugosità dovuta alla presenza delle forme di fondo, ed in particolare dovuta alle dune. I dati ottenuti indicano che l’apporto solido fluviale dei fiumi studiati è molto variabile ed in particolare il trasporto solido dei Fiumi Uniti è superiore a quello del fiume Savio. Infine, è stato eseguito un confronto tra dati misurati sul campo e quelli ottenuti da criteri ben noti di letteratura allo scopo di definire la migliore equazione utilizzabile a scala regionale per quantificare l’apporto solido fluviale alle spiagge romagnole