Stimulated Expression of CXCL12 in Adrenocortical Carcinoma by the PPARgamma Ligand Rosiglitazone Impairs Cancer Progression

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis when metastatic and scarce treatment options in the advanced stages. In solid tumors, the chemokine CXCL12/CXCR4 axis is involved in the metastatic process. We demonstrated that the human adrenocortex expressed CXCL12 and its cognate receptors CXCR4 and CXCR7, not only in physiological conditions, but also in ACC, where the receptors' expression was higher and the CXCL12 expression was lower than in the physiological conditions. In a small pilot cohort of 22 ACC patients, CXCL12 negatively correlated with tumor size, stage, Weiss score, necrosis, and mitotic activity. In a Kaplan-Meier analysis, the CXCL12 tumor expression significantly predicted disease-free, progression-free, and overall survival. In vitro treatment of the primary ACC H295R and of the metastatic MUC-1 cell line with the PPARγ-ligand rosiglitazone (RGZ) dose-dependently reduced proliferation, resulting in a significant increase in CXCL12 and a decrease in its receptors in the H295R cells only, with no effect on the MUC-1 levels. In ACC mouse xenografts, tumor growth was inhibited by the RGZ treatment before tumor development (prevention-setting) and once the tumor had grown (therapeutic-setting), similarly to mitotane (MTT). This inhibition was associated with a significant suppression of the tumor CXCR4/CXCR7 and the stimulation of human CXCL12 expression. Tumor growth correlated inversely with CXCL12 and positively with CXCR4 expression, suggesting that local CXCL12 may impair the primary tumor cell response to the ligand gradient that may contribute to driving the tumor progression. These findings indicate that CXCL12/CXCR4 may constitute a potential target for anti-cancer agents such as rosiglitazone in the treatment of ACC

Clinical correlates of "pure" essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Clinical assessment instruments validated for nursing practice in the Italian context: a systematic review of the literature

Aims. With the aim to identify the instruments validated for Italian nursing practice, a systematic review of the literature was undertaken.Results. A total of 101 instruments emerged. The majority (89; 88.1%) were developed in other countries; the remaining (14; 13.9%) were developed and validated in the Ital-ian context. The instruments were developed to measure patient’s problems (63/101; 62.4%), outcomes (27/101; 26.7%), risks (4/101; 4%) and others issues (7/101; 6.9%). The majority of participants involved in the validation processes were younger adults (49; 48.5%), older adults (40; 39.5%), children (4; 4%), adolescents (3; 3%), and children/adolescents (1; 1%). The instruments were structured primarily in the form of questionnaires (61; 60.4%), as a grid for direct observation (27; 26.7%) or in other forms (12; 11.9%). Among the 101 instruments emerged, there were 1 to 7 validation measures documented with on average 3.2 (95% CI 2.86-3.54) for each instrument.Conclusions. Developing validation studies giving priority to those instruments widely adopted in the clinical nursing practice is recommended.  

Clinical correlates of “pure” essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk

L'antica Cattedrale di Roselle (GR): il dibattito storiografico e i materiali degli scavi 1987-1991. Rilettura e aggiornamento dei dati.

In questa tesi verranno presentati alcuni materiali ancora inediti provenienti dagli scavi eseguiti a Roselle (Grosseto) tra il 1987 e il 1991, nell’area delle antiche terme adrianee, interessata da un riutilizzo a scopo cimiteriale a partire dall’età altomedievale (VI-VIII secolo). Il cimitero in questione era pertinente alla chiesa che sorgeva proprio sui ruderi degli antichi ambienti delle terme, opportunamente riadattati in funzione della nuova struttura . Verrà inoltre affrontato il problema, a lungo dibattuto, dell’esatta ubicazione della più antica Cattedrale di Roselle, che negli anni passati ha dato luogo ad un acceso dibattito tra gli studiosi di storia locale. Lo scopo di questo lavoro è di attualizzare e aggiornare lo stato degli studi ad oggi, facendo una sintesi delle varie interpretazioni elaborate nell’arco di oltre 20 anni di ricerche e proporre eventuali interpretazioni personali, senza avere la pretesa di voler raggiungere una soluzione definitiva che ponga fine alle controversie sorte sull’argomento

Risultati clinici e radiografici nell'uso di uno stelo femorale non cementato rivestito di idrossiapatite nell'anziano: studio multicentrico

L’intervento di protesi d’anca, definito “intervento del secolo” dalla rivista Lancet, è da sempre oggetto di grande interesse e fermento scientifico; dalla prima protesi d’anca di Charnley negli anni ’60, le innovazioni tecniche e procedurali sono state innumerevoli, non solo in termini di approccio chirurgico, ma anche in termini di materiali e di design protesici. Dati ISTAT riportano un aumento della vita media per entrambi i generi, giungendo a 86,1 anni e 90,2 anni, rispettivamente per uomini e donne (80,6 e 85 anni nel 2016) entro il 2065, con un picco di invecchiamento che colpirà l’Italia nel 2045-50, quando si riscontrerà una quota di ultrasessantacinquenni vicina al 34%. L’aumento della longevità della popolazione richiederà, quindi, un incremento della necessità di ricorrere a sostituzione con protesi totale d’anca per il trattamento di fenomeni osteoartrosici che sono presenti in prevalenza nei pazienti anziani. È proprio in questa tipologia di paziente, spesso soggetto ad avere comorbidità ed essere quindi un soggetto fragile, che in letteratura è ancora aperto il dibattito su quale sia il miglior tipo di impianto protesico, in particolare se sia meglio una protesi con stelo cementato oppure non cementato. Gli steli cementati, infatti, prevedendo l’utilizzo del polimetilmetacrilato (PMMA), che, come una malta, determina un accoppiamento ad incastro tra l’osso spongioso e la protesi, vengono quindi spesso ritenuti gli impianti di scelta nel paziente con scarsa qualità ossea, tipica del paziente anziano. Dall’altro lato, l’utilizzo degli steli non cementati, realizzati con superfici tali da favorire il bone Ongrowth e Ingrowth, viene invece proposto per il paziente giovane e con buona qualità ossea. Come accennato precedentemente, e come spesso succede in medicina, queste affermazioni non sono assolute, ecco così il crescere di una recente letteratura ed attenzione circa la possibilità di scegliere un impianto non cementato anche nel paziente anziano. L’intento di questa tesi è volto a dimostrare la sopravvivenza, i risultati clinici e i risultati radiografici a medio-lungo termine di uno stelo femorale non cementato, con doppio rivestimento plasma spray in titanio poroso e idrossiapatite (stelo Exacta HAX-Pore – Permedica) impiantato in una coorte di pazienti over 70 operati presso i reparti di Ortopedia e Traumatologia di Pisa e il reparto di Ortopedia e Traumatologia dell’ospedale Versilia

Re-localisation of food, re-qualification of places and landscape protection:A case study from the Parco Agricolo Sud Milano, Italy.

This paper discusses the complex interrelations between the quality of food and places, and landscape protection. The growing interest for the re-localisation of food is accompanied by an increased awareness that the food system is a strategic point of view to understand and direct the determinants of development at global as well as regional and local levels, entailing economic, social and environmental benefits. By exploring these issues, the paper offers an analysis of the web-marketing strategies of a group of farms located within the Parco Agricolo Sud Milano (IT) and certified through the Environmental Quality Mark, in order to test if and how they create a link between quality of places and quality of food, and which values they use to explain this link. The analysis confirms the role of the mark in promoting a reconnection between food and its place of production, i.e. the Park, as well as supporting the diffusion of environmental values and the development and attractiveness of the area. The paper highlights how the integration of multifunctional agriculture and values typical of alternative economic spaces into spatial planning and landscape preservation could be a good instrument for policy makers in order to lay the foundations for the development of both new environmental-oriented food policies and sustainable agricultural landscape planning