Metastatic Renal Cell Carcinoma Rapidly Progressive to Sunitinib: What to Do Next?

Background: From 10% to 26% of patients with metastatic renal cell carcinoma (mRCC) experience rapidly progressive disease (PD) on treatment with sunitinib. Objective: To investigate the benefit of subsequent treatment with another tyrosine kinase inhibitor (TKI) or a mammalian target of rapamycin (mTOR) inhibitor in such primary refractory patients. Design, setting, and participants: A total of 150 mRCC patients with rapidly PD on first- line sunitinib (within two cycles, n = 93, or four cycles, n = 57) were identified: median age 59 yr; nephrectomy 86%; histological subtypes: clear cell (77.8%), papillary (14%), and sarco- matoid features (18%); according to the Memorial Sloan-Kettering Cancer Center and French classifications: good risk (11% and 7%, respectively), intermediate (68% and 63%, respectively), and poor (21% and 29%, respectively). Outcome measurements and statistical analysis: Data were retrospectively collected by a questionnaire from 19 European oncology centers between March 2005 and March 2011. Pro- gression-free survival (PFS) and overall survival (OS) were calculated (Kaplan-Meier method). Results and limitations: Median OS from the start of first-line treatment was 7.4 mo. Second-line treatment was administered to 86 (57%) patients (44 mTOR inhibitors: 23 ever- olimus and 21 temsirolimus; 39 TKIs alone or in combination; three chemotherapy). Second- line PFS was not significantly different between TKIs and mTOR inhibitors (2.0 vs 0.9 mo; p = 0.536). Median OS from the start of second-line treatment was 5.0 mo for mTOR inhibitors and 6.6 mo for TKIs (p = 0.15). Conclusions: Treatment with further TKIs or mTOR inhibitors for mRCC patients primarily refractory to first-line sunitinib in the observed time period achieved very minimal benefit, suggesting avoiding TKI rechallenge and possibly preferring alternative strategies, such as immune checkpoint inhibitors, after PD to a treatment line including a TKI in this setting. Patient summary: The present work collected data about 150 patients affected by meta- static renal cell carcinoma, who received one of the current standard of care as first-line treatment, namely, the antiangiogenic drug sunitinib, and experienced rapid worsening of the disease. We investigated and described the subsequent outcome of such patients treated with two different types of drug, administered as second-line therapy, to better understand the best strategy to adopt for patients who got no benefit from sunitinib and to describe the current therapeutic approach in such cases

An international tool to measure perceived stressors in intensive care units: the PS-ICU scale.

Background The intensive care unit is increasingly recognized as a stressful environment for healthcare professionals. This context has an impact on the health of these professionals but also on the quality of their personal and professional life. However, there is currently no validated scale to measure specific stressors perceived by healthcare professionals in intensive care. The aim of this study was to construct and validate in three languages a perceived stressors scale more specific to intensive care units (ICU). Results We conducted a three-phase study between 2016 and 2019: (1) identification of stressors based on the verbatim of 165 nurses and physicians from 4 countries (Canada, France, Italy, and Spain). We identified 99 stressors, including those common to most healthcare professions (called generic), as well as stressors more specific to ICU professionals (called specific); (2) item elaboration and selection by a panel of interdisciplinary experts to build a provisional 99-item version of the scale. This version was pre-tested with 70 professionals in the 4 countries and enabled us to select 50 relevant items; (3) test of the validity of the scale in 497 ICU healthcare professionals. Factor analyses identified six dimensions: lack of fit with families and organizational functioning; patient- and family-related emotional load; complex/at risk situations and skill-related issues; workload and human resource management issues; difficulties related to team working; and suboptimal care situations. Correlations of the PS-ICU scale with a generic stressors measure (i.e., the Job Content Questionnaire) tested its convergent validity, while its correlations with the Maslach Burnout Inventory-HSS examined its concurrent validity. We also assessed the test–retest reliability of PS-ICU with intraclass correlation coefficients. Conclusions The perceived stressors in intensive care units (PS-ICU) scale have good psychometric properties in all countries. It includes six broad dimensions covering generic or specific stressors to ICU, and thus, enables the identification of work situations that are likely to generate high levels of stress at the individual and unit levels. For future studies, this tool will enable the implementation of targeted corrective actions on which intervention research can be based. It also enables national and international comparisons of stressors’ impact.post-print925 K

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Specific treatment of benzodiazepine overdose.

Intentional benzodiazepine (BZD) overdose is usually a benign condition frequently encountered in the emergency department of hospital. Twenty-one patients, who were suspected of BZD overdose, were treated with the antagonist of the central type BZD-receptors Ro 15-1788. Samples for toxicological analysis were taken before and after treatment. The patients were divided into three groups. In the first group (pure BZD overdose, n = 9), rapid and complete awakening was observed in all the patients (9/9) with 3.5 +/- 1.5 mg Ro 15-1788. In the second group of patients with multiple drugs poisoning (including BZD, n = 6), CNS depression improved in all the patients despite incomplete awakening. In the last group (n = 6), where no BZD were detected in toxicological samples, none of the comatous patients improved significantly during Ro 15-1788 administration, except one patient with pure ethanol intoxication. No undesirable effects are reported, except mild transitory withdrawal syndrome in three cases following rapid injection. This study supports the introduction of Ro 15-1788 as a useful antidote in the diagnosis and the treatment of drug-induced coma.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe