Role of Acute Graft-Versus-Host Disease in the Risk of Bacteremia and Invasive Fungal Disease after Allogeneic Hemopoietic Stem Cell Transplantation in Children. Results from a Single-Center Observational Study

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Rivaroxaban-induced hepatotoxicity: review of the literature and report of new cases

Aim/Objective/Background Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. Methods A systematic search of case reports on the MEDLINE database encompassing the years 2008–2016 was carried out.Additional references were obtained following a manual search of the retrieved papers. We report two new cases of adverse events occurred in patients treated with rivaroxaban (20 mg/die) to prevent systemic embolism, who presented with hepatocellular liver injury with onset at 8 weeks after initiation of the drug intake. Results Twenty-six cases were retrieved from MEDLINE (57.7% female, 42.3% male). Using the Roussel Uclaf Causality Assessment Method (RUCAM) scale, liver injury was classified as hepatocellular (42.3%), cholestatic (26.9%), or mixed (15.4%). Older age (≥65 years) was present as a risk factor in 57.7%. The time lapse between initiation of treatment and onset of hepatic injury ranged from 2 to 180 days (median: 15 days). Our two new patients were diagnosed with drug-induced liver injury (hepatocellular pattern) using the ‘consensus criteria’, for drug-induced liver injury. Their RUCAM scores were calculated and assessed as highly probable and probable, respectively. A clinical recovery after rivaroxaban withdrawal was observed. Conclusion Direct-acting oral anticoagulants have been commonly prescribed, even if safety issues regarding the use of these drugs are still an ongoing concern, especially in patients experiencing chronic liver disease. Dedicated postauthorization safety studies should be undertaken to better define rivaroxaban-induced drug-induced liver injury

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Farmacovigilanza in oncologia: la nostra esperienza nel "Centro di consulenza ed informazione sugli effetti tossici da farmaci antitumorali e sulle ADR in pazienti neoplastici" della Regione Sicilia

La segnalazione delle reazioni avverse da farmaci (ADR) in ambito post-marketing è fondamentale per la tempestiva identificazione di nuove, in particolare gravi, tossicità, che, non emergono facilmente nei trial pre-registrativi.per vari limiti. La farmacovigilanza (FV) è necessaria per una identificazione più completa della sicurezza e dell’impatto sulla qualità di vita di un nuovo medicamento nella pratica clinica reale, dove i pazienti, per differenti ragioni (patologie multiple, corredo genetico, usi off-label, etc.) sono a maggior rischio di ADR e di interazioni tra farmaci. In passato i farmaci antineoplastici non sono stati oggetto di attenzione prioritaria nei programmi nazionali o internazionali di FV e, in aggiunta, è stata assente la cultura della segnalazione delle ADR tra gli oncologi medici. Solo recentemente è stato sottolineata la chiara, preminente, importanza delle attività di FV in ambito oncologico; si assiste ad un rapido ed intenso sviluppo di nuovi agenti, tra cui quelli a meccanismo non tradizionale (inibitori kinasici, anticorpi monoclonali), e tutta una serie di significativi problemi inaspettati ha indicato come ci sia ancora molto da imparare sul loro profilo di tossicità. Dal gennaio 2003, la Regione Sicilia ha attivato un Progetto per l’Organizzazione della FV in Sicilia, che è stato successivamente adeguato all'evoluzione della normativa comunitaria e nazionale nel settore. Fin dall’inizio, il Progetto si è fortemente interessato all’oncologia con l’istituzione di un Centro dedicato, finalizzato principalmente ad aumentare la quantità e la qualità delle segnalazioni in questo campo anche attraverso l’invio di informazioni di ritorno ai segnalatori ed altre iniziative educazionali. In base ai dati della rete nazionale di FV, nel corso degli anni in Sicilia il numero delle segnalazioni è aumentato, passando da quattro (sic!) nel 2002 a cinquanta nel 2008. Questo risultato non è ancora soddisfacente, ma in genere le segnalazioni sono state di notevole interesse e buona qualità, come dimostrato anche dalla percentuale (49% delle 126 segnalazioni complessive) di ADR definite gravi secondo i criteri OMS. Nel 2006, l’AIFA ha istituito il Registro dei Farmaci Oncologici sottoposti a Monitoraggio (RFOM) con lo scopo di consentire da una parte la verifica dell’appropriato uso di questi farmaci (nei regimi a “risk sharing”, anche ai fini del rimborso in base al risultato da parte delle case farmaceutiche), dall’altra di raccogliere dati utili ad integrare le conoscenze emerse dai trial pre-registrativi. Per evitare al medico doppie incombenze, dal marzo 2008 gli utenti dell’RFOM devono utilizzare un apposito modulo web in grado di generare le schede di segnalazione delle ADR, da impiegare per tutti gli scopi di FV previsti dalla normativa vigente. Verrà riferito come, per alcune incomprensioni o addirittura resistenze, l’RFOM stenta, almeno in Sicilia, a dare i frutti sperati nel campo della FV

Protocol of BRONJ prevention: successful use of antiseptics during oral surgical procedures

Aim: The overall prevention and treatment of Bisphosphonates related osteonecrosis of the jaws (BRONJ) have been the goals of our project structured (labelled PROMaB) within the hospital AOUP “P. Giaccone” (Italy) in order to make better quality life of patients in therapy with amminobisphosphonates (NBP). Material and Methods: Among all procedures, in case of preprogrammed oral surgical procedure, oral antimicrobial rinses (i.e. chlorexidine 0,2% mouthwash and 0,5% gel, three times/day) plus oral systemic antibiotic therapy –e.g. amoxicilin/clavulanate- have been used to reduce the risk of BRONJ in secondary prevention (1 day before and 6 days after). Three hundred and twenty-one patients (206 F and 115 M; range 45-85 yrs; mean age 62,3) under treatment with NBP (80 ev vs 241 os) have been recruited for dental examination Results: 412 dental extractions have been carried out. From 2007 up to date, after application of preventive protocol, only 5 cases of BRONJ (based on clinical and radiological features) have been observed; the follow up was at least 2 years. Three patients with BRONJ were treated with zolendronic acid (1 for multiple mieloma, 1 for bone metastasis, 1 for osteoporosis in off label) and showed some risk factors; one female was in treatment with pamidronate for osteoporosis, and had coagulopathy; the last one suffered from osteoporosis treated with alendronate and clodronate. Conclusion: In conclusion, despite study limitation, this protocol could be an easy protocol during dental treatment among NBP patien

Isolated Nodal TBC Reactivation in a Patient with Post-Thrombocythemia Myelofibrosis Treated with Ruxolitinib: Case Report and Review of the Literature

Ruxolitinib side effects include the most frequent hematological toxicity along with a more recently evidenced immunosuppressive activity, interfering both with the innate and adaptive immunity, and several cases of reactivation of latent infections by opportunistic agents in patients in treatment with ruxolitinib have been published in the last years. Several pathophysiological mechanisms may explain an association between ruxolitinib and opportunistic infections. From what we know, the only case of an isolated lymph node TBC reactivation in a ruxolitinib-treated myelofibrosis (MF) patient was reported by Patil et al. in 2016 [Int J Med Sci Public Health. 2017;6(3):1]. Other 10 cases describing TBC reactivations in MF patients assuming ruxolitinib and successfully treated with 4-drug anti-TBC therapy are available in the literature to date. The case we reported describes an isolated lymph nodal TBC reactivation in a patient with the diagnosis of post-essential thrombocythemia-MF during ruxolitinib treatment after a long course of interferon-a (IFN-alpha2b) assumed for the previous diagnosis of ET. The case we report teaches that lymphadenopathy with or without constitutional symptoms developing during ruxolitinib therapy should be considered as a possible manifestation of a TBC reactivation in patients with a previous positive TBC-exposure test. In these cases, Ziel-Nielsen testing on urine and sputum has to be performed to rule out infectiousness and eventually isolate the patient. Moreover, previous long-time exposition to IFN-alpha2b may be related with a higher risk for TBC reactivation in these subset of patients. We encourage reevaluation of the cohorts of patients treated with ruxolitinib in previous and current large prospective studies to study the possible correlation between previous exposition to IFN-alpha2b and TBC reactivation

Could the Combined Administration of Bone Antiresorptive Drug, Taxanes, and Corticosteroids Worsen Medication Related Osteonecrosis of the Jaws in Cancer Patients?

The study presents a report of 58 metastatic cancer patients who developed osteonecrosis of the jaws after being treated with zoledronic acid and taxanes, plus corticosteroids. A retrospective analysis of data registered in the archives of two Italian osteonecrosis of the jaws treatment centers, who are based at the University of Messina and at the University of Palermo, was performed in order to study, in these patients, demographic data and characteristics such as frequency of cancer location, lines of therapy, frequency of cancer drugs, presence/absence of oral trigger, number, location, and stage of jaw osteonecrosis. It was found that the majority of patients developed advanced stages of osteonecrosis, frequently complicated with infection. It was hypothesized that the concurrent administration of chemotherapeutic agents could be eventually considered as a factor able to allow a faster worsening of the clinical manifestation through the exacerbation of soft tissue defects, due to chemotherapy drugs