26 research outputs found

    Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors

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    open57noIMPORTANCE Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. OBJECTIVE To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. EXPOSURES Upfront PRRT or upfront chemotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. RESULTS Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95%CI, 2.3-3.0 years] vs 0.7 years [95%CI, 0.5-1.0 years]; HR, 0.35 [95%CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95%CI, 0.4-1.0 years]; HR, 0.37 [95%CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95%CI, 10.7-14.1 years] vs 11.6 years [95%CI, 9.1-13.4 years]; HR, 0.81 [95%CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95%CI, 9.2-17.9 years]; HR, 0.83 [95%CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95%CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95%CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95%CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95%CI, 0.12-0.34]; grade 2: aHR, 0.52 [95%CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95%CI, 0.24-0.61]; intestinal: aHR, 0.19 [95%CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95%CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95%CI, 0.29-1.43; P = .31). CONCLUSIONS AND RELEVANCE In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.openPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, FilippoPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, Filipp

    Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database

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    : Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)

    Valutazione dell'Obesita Ginoide: Un Nuovo Approccio Geometrico con Validazione Densitometrica

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    Nel settore nutrizionale, le visite svolte dai medici o dai biologi nutrizionisti, si limitano a esaminare la parte superiore del corpo del paziente, escludendo completamente le gambe dalla valutazione antropometrica. L’obiettivo del presente studio è quello di validare una tecnica da noi messa a punto per la misura del volume delle gambe, da poter aggiungere alle valutazioni abituali che si fanno in ambito ambulatoriale. La tecnica deve essere quindi semplice e rapida; si tratta infatti della misura tramite metro da sarta del diametro della gamba in 4 punti specifici e la misura dell’altezza della parte misurata. Tramite questi dati è possibile trovare il volume totale con metodo geometrico, considerando la gamba come un cono troncato. Questa tecnica era stata validata da Lennihan e Mackereth nel 1973 ma riguardava solo la parte sotto il ginocchio. Qui abbiamo ampliato la misura considerando anche la coscia e abbiamo validato il volume calcolato confrontandolo con la tecnica gold standard per la misura volumetrica dei diversi settori del corpo, cioè la DEXA (densitometria).Per ogni paziente (n=25), i volumi calcolati geometricamente sono poi stati messi a confronto con i volumi ottenuti con la dexa. I risultati sono stati validati tramite regressione lineare con la quale si ottiene un R2 di 0.4. Dal test T-Student svolto, emerge un P-value di 0,824, che conferma il nuovo metodo analizzato

    Pension reform and household financial position

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    In recent times pension reforms oriented toward introducing or expanding pension funds or insurance have been implemented in many countries. The main reason for this change is to reinforce the sustainability of intergenerational redistribution due to the ageing of society. However, a secondary aim has also been that of helping the development of financial markets and expanding the role of the stock exchange. We will focus on developed countries and, more specifically, on European pension reforms. A number of questions arise concerning the impact of such reforms. In particular, we will deal with the change in household savings investment and with the impact that these reforms have on the financialisation of the economy

    Clinical and patient‐centered outcomes post non‐surgical periodontal therapy with the use of a non‐injectable anesthetic product: A randomized clinical study

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    Abstract AIM: The aim of this study was to determine the impact of different full-mouth decontamination (FMD) protocols on the effectiveness of an intrapocket anesthetic gel in periodontal maintenance patients. METHODS: Patients undergoing the periodontal maintenance program and with the need for FMD participated in this study. Patients were randomly allocated to non-surgical periodontal therapy (NSPT) with either a preparatory 15-day decontamination phase, including chlorhexidine mouth rinse and domiciliary hygiene instructions (modified FMD: test group), or without it (FMD: control group). In both groups, NSPT was performed with the aid of a non-injectable anesthetic gel. Clinical and patient-related outcomes were recorded during a 6-month follow-up period. RESULTS: Sixty patients completed the 6-month study. Both groups experienced relevant clinical improvements after NSPT, but the test group showed a significant change in periodontal parameters already after the initial 15-day preparatory period, and overall significantly better results in periodontal outcomes when compared with the control group at the last 6-month follow up: the gingival index was 2.07 ± 1.25 in the control group and 1.13 ± 0.51 in the test group. Less pain and dental-related anxiety were perceived by patients in the test group showing a 6-month mean visual analog scale of 2.13 ± 1.25 in the control group and 1.13 ± 0.83 in the test group. CONCLUSION: The present study suggested that the modification of the standard FMD could improve the clinical efficacy of non-injectable anesthetic, along with patients' short- and mid-term appreciation and compliance

    Propolis as an adjuvant to non-surgical periodontal treatment: a clinical study with salivary anti-oxidant capacity assessment.

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    Abstract BACKGROUND: Periodontal diseases are characteristic for the excessive release of oxidant free-radicals by the host. The aim of the present study was to evaluate the efficacy of an anti-oxidant-based formula containing propolis and herbs as an adjunctive therapy to standard non-surgical periodontal treatment (NSPT) when compared to the domiciliary use of chlorhexidine-based formulae. METHODS: Forty patients were enrolled in the present study and randomly allocated to either a control (NSPT plus chlorhexidine gel formula) group or a test (NSPT plus anti-oxidant gel formula) group. Clinical parameters for the assessment of the periodontal status were evaluated at baseline, one month, and three months after NSPT, and the salivary antioxidant capacity as well. RESULTS: There were no significant clinical differences between the two groups (P>0.05). However, patients within the test group (propolis) achieved better results in terms of oxidative stress reduction (P<0.05). CONCLUSIONS: In the present study, propolis was comparable to chlorhexidine in the clinical management of gingivitis. Further studies are needed to investigate its potential as a redox modulator for the oral microbiome

    Combination of immunotherapy and other targeted therapies in advanced cutaneous melanoma

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    Cutaneous Melanoma (CM) is an aggressive cancer whose incidence is increasing worldwide. However, the knowledge of its biology and genes driving cell growth and survival allowed to develop new drugs that have improved PFS and OS of advanced disease. Both BRAF targeting agents and immune checkpoint inhibitors (ICIs) have been adopted for the treatment of metastatic disease and the adjuvant setting. Several melanoma patients show innate or acquired drug-resistance and thus new strategies are required for overcoming this complication. New ICIs have been developed, and strategies of combination or sequencing are under investigation in ongoing clinical trials. In addition, pre-clinical data have demonstrated that many strategies induce the release of neoantigens within the tumor microenvironment, thus suggesting the combination of new agents with ICIs. Here, we review the ongoing strategies in advanced CM including a dedicated section on treatment of brain metastases

    Diabetes mellitus induced by somatostatin analogue therapy is not permanent in acromegalic patients

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    CONTEXT: Therapy with somatostatin analogues (SSAs) may have deleterious effects on glucose metabolism in patients with acromegaly, often leading to the development of diabetes mellitus (DM). AIM: The aim of the study was to evaluate whether DM, developed during therapy with SSAs, may revert after drug withdrawal and cure of acromegaly with pituitary adenomectomy. DESIGN: Retrospective cohort study, in a tertiary referral centre. PATIENTS: Eighteen acromegalic patients without DM at the diagnosis of acromegaly treated with SSAs as a primary therapy, and then cured by pituitary adenomectomy. METHODS: Endocrine status and glucose homeostasis were evaluated at diagnosis of acromegaly and at least every 6 months during SSA therapy. At each visit, patients were classified into one of the following classes: normal glucose tolerance, prediabetes, overt diabetes. RESULTS: Median follow-up after starting SSAs therapy was 69 months (IQR 54.75-132.25). During SSA therapy, all patients had controlled acromegaly defined by normal serum IGF1 concentrations for the age. Of the 13 euglycaemic patients at diagnosis, three developed prediabetes and three diabetes, whereas, of the five prediabetic patients at diagnosis, two worsened to overt diabetes and three remained in the prediabetic range (P = 0.04). After curing acromegaly with pituitary adenomectomy and subsequent SSA withdrawal, prediabetes reverted in five of six patients, and diabetes in all five patients (three reverted to euglycaemia, while two reverted to prediabetes) (P = 0.01). CONCLUSIONS: In acromegalic patients with controlled disease, changes in glycaemic status induced by SSAs are not permanent

    A ntibiotic treatment to prevent postextraction complications: A monocentric, randomized clinical trial. Preliminary outcomes

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    BAC KGRO UND: Tooth extraction is a very common procedure in oral surgery. Despite this, very little information is available in the literature as to the antibiotic management of the patient. The aim of this study is to evaluate whether the antibiotic prophylaxis could be beneficial in preventing postextraction local complications and whether the use of a probiotic could help reduce the antibiotic gastro-intestinal side effects. METHODS: One hundred eleven patients meeting the inclusion criteria were initially included in this randomized clinical trial and randomly allocated to one of the three experimental groups according to a computer-generated randomization list. Patients allocated to the group 1 were given amoxicillin+clavulanic acid (2 g/day for 6 days), patients allocated to the group 2 received antibiotic + probiotic (Bifidobacterium longum+lactoferrin) and patients allocated to the group 3 received no antibiotic therapy after the extraction. To evaluate post-extractive complications, controls were performed at days 7, 14 and 21 after the extraction. RESULTS: At T1 pain at the surgical site was present in the 48%, 30% and 71.4% of the patients belonging respectively to the antibiotic alone group, to the antibiotic+probiotic group and to the control group. The mean Numeric Rating Score (NRS) score was 1.56±1.91, 1.08±1.93, 2.02±2.27 respectively (P=0.0498). Two patients belonging to the control group experienced dry socket. In addition, 9 patients (33.3%) in the antibiotic-alone group and 1 patient (2.7%) in the antibiotic+probiotic group reported intestinal distension (P=0.0012), 7 days after surgery. Finally, diarrhea was recorded in 5 patients of the antibiotic alone group (18.5%), on the other hand, no patients of the antibiotic+probiotic group and the control group reported diarrhea. CONCL USION S: Postextractive complications observed in each group have been mild and fast to resolve. The antibiotic administration showed a decrease in pain suffered by patients but a higher incidence of gastrointestinal side effects, such as abdominal distension and diarrhea, which seemed to be relieved by the concomitant use of the probiotic
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