REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma.

BACKGROUND: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. PATIENTS AND METHODS: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs). RESULTS: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O6-methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs. CONCLUSIONS: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study.

[Theory models of burnout: aspects of risk assessment and preventives measures in health care operators]. / Modelli teorici del burnout: aspetti di valutazione del rischio e provvedimenti di ordine preventivo in operatori sanitari.

The figures appointed to prevention is to assess all the risks and working notes that the more complex when you take into consideration the risks related to the organization of work, especially in certain types of work in which a proper assessment can not ignore the intrinsic problems of the job done. The studies that have been employed in particular health professions speak of a phenomenon of job stress response called "Syndrome Burnout." Our study includes a description of current research, in literature, made on the issue and particularly on the theoretical models of Burnout (Models of competence / effectiveness--psychosocial Models--phases of Burnout); Below is sought to draw in some health care workers, "the individual characteristics" of the subjects that I am concerned, identify the causes and effects, outline proposals for action for risk assessment, defining prevention measures, for the early identification of symptoms, acting on variables that affect the occurrence of the syndrome.

[Behavior of fibrinogen-split-product-E in fibrinuria following allogeneic kidney transplantation (author's transl)]. / Zum Verhalten des Fibrinogenspaltproduktes-E während der Fibrinurie nach allogener Nierentransplantation

80 urine samples from 10 kidney grafted patients were immunologically analyzed for detection of fibrin degradation products by various techniques. Split product E, which was quantitatively determined by two-dimensional immunoelectrophoresis only contributes to a minor part to fibrinuria, but increases significantly during periods of severe acute rejection also during the first 2-3 weeks, when overall fibrinuria is not a useful indicator of impending rejection. Determination of split-product E therefore seems to be a valuable diagnostic procedure.

Clinical significance of fibrinuria with fibrinogen split-product E following kidney allotransplantation.

Typical findings of disseminated intravascular coagulation were found in patients following kidney allotransplantation where quantitative determinations revealed fibrin degradation products in the urine. Split-product E, which was quantitatively determined in urine samples, contributes to this fibrinuria. Elevated levels of fibrinogen split products in serum as well as in urine are detectable several days prior to clinical signs of rejections and serve as an early indicator of impending rejection in patients with renal allografts.