[Evaluation of practices through simulation: Implementation of Horror Week in a cytotoxic preparation unit]. / Évaluation des pratiques par simulation : mise en place de la semaine de l'horreur dans une unité de préparation de cytotoxiques.

OBJECTIVES: The objective of this work is to describe the interest of developing a simulation for the evaluation and improvement of practices through the realization of a horror week in a cytotoxic preparation unit. METHODS: The simulation was divided into five days, each corresponding to a step in the cytotoxic circuit. Five errors per day were produced and presented to the team in a dedicated room. An observation form was used to collect the errors identified by each person. A satisfaction questionnaire was distributed and a collective debriefing took place remotely. RESULTS: The average number of errors identified per day was 3.8. The least common errors were reversal of patient height and weight, overloading of the sterilization basket, failure to follow dressing rules in the controlled area, absence of the temperature-monitoring disk, and absence of an opaque bag for photosensitive chemotherapy. The perceived level of difficulty was 3.33/5 and the organization was satisfactory to all participants. CONCLUSIONS: Horror Week achieved its objectives by raising awareness among professionals of the risks of the chemotherapy circuit. The errors that were found to be the least significant allowed us to develop priority areas for ongoing training for our unit.

Use of speckle tracking echocardiography to detect late anthracycline-induced cardiotoxicity in childhood cancer: A prospective controlled cross-sectional study.

BACKGROUND: This study aimed to detect late sub-clinical patterns of cardiac dysfunction using speckle tracking echocardiography (STE) in children with cancer remission more than 12 months after the end of anthracycline treatment. METHODS: This prospective controlled study enrolled 196 children, 98 of which had been treated with anthracyclines (mean age 10.8 ± 3.6 years; 51% female) and 98 were age- and gender-matched healthy subjects in a 1:1 case-control design. Conventional echocardiographic variables were collected for left ventricle (LV) and right ventricle (RV). STE analyses were performed in the LV longitudinal, radial, and circumferential displacements and in the RV free wall longitudinal displacement. The association between LV global longitudinal strain (GLS) and the main clinical and biological parameters was evaluated. RESULTS: After a mean time interval of 5.1 ± 3.2 years since the end of chemotherapy (mean cumulative anthracycline dose of 192 ± 96 mg/m2), conventional echocardiographic measures were normal. GLS was significantly decreased in the anthracycline group (-19.1% vs. -21.5%, P < 0.0001), with a higher proportion of children with abnormal values (Z-score < -2 in 18.6% vs. 1.0%, P < 0.0001). No association was found between GLS and clinical or biological parameters. Circumferential strain was significantly worse in the anthracycline group (-16.8% vs. -19.4%, P < 0.0001), and radial strain significantly better (+51.4% vs. +35.9%, P < 0.0001). RV conventional echocardiography and STE parameters were normal and not different between anthracycline and control groups. CONCLUSIONS: The existence of a modified LV strain despite normal LV function in children treated with anthracyclines represents an important perspective for cardiomyopathy surveillance in childhood cancer survivors. Clinical Trial Registration -ClinicalTrials.gov Identifier: NCT02893787.

Screening for in-vivo regional contractile defaults to predict the delayed Doxorubicin Cardiotoxicity in Juvenile Rat.

Anthracyclines are key chemotherapeutic agents used in various adult and pediatric cancers, however, their clinical use is limited due to possible congestive heart failure (HF) caused by acute and irreversible cardiotoxicity. Currently, there is no method to predict the future development of the HF in these patients. In order to identify early biomarkers to predict anthracycline cardiotoxicity in long-term survivors of childhood cancer, this longitudinal study aimed to analyze early and late in-vivo regional myocardial anthracycline-induced cardiotoxicity, related to in-vitro cardiac myocytes dysfunction, in a juvenile rat model. Methods: Young male Wistar rats (4 weeks-old) were treated with different cumulative doses of doxorubicin (7.5, 10 or 12.5 mg/kg) or NaCl (0.9%) once a week for 6 weeks by intravenous injection. Cardiac function was evaluated in-vivo by conventional (left ventricular ejection fraction, LVEF) and regional two-dimensional (2D) speckle tracking echocardiography over the 4 months after the last injection. The animals were assigned to preserved (pEF) or reduced EF (rEF) groups at the end of the protocol and were compared to controls. Results: We observed a preferential contractile dysfunction of the base of the heart, further altered in the posterior segment, even in pEF group. The first regional alterations appeared 1 month after chemotherapy. Functional investigation of cardiomyocytes isolated from the LV base 1 month after doxorubicin treatment showed that early in-vivo contractile alterations were associated with both decreased myofilament Ca2+ sensitivity and length-dependent activation. Changes in post-translational modifications (phosphorylation; S-glutathionylation) and protein degradation of the cardiac myosin binding protein-C may contribute to these alterations. Conclusion: Our data suggest that screening of the contractile defaults of the base of the heart by regional 2D strain echocardiography is useful to detect subclinical myocardial dysfunction prior to the development of delayed anthracycline-induced cardiomyopathy in pediatric onco-cardiology.

Adverse reactions related to brentuximab vedotin use: A real-life retrospective study.

Post-marketing data regarding brentuximab vedotin (BV) are sparse. The aim of this study was to assess the frequency and nature of significant adverse drug reactions (ADRs) in patients treated with BV in a real-world setting. We conducted a systematic retrospective study of patients treated with BV in a French university hospital. Significant ADRs were collected using the electronic patient records. Between January 2009 and December 2016, 39 patients received BV. Median age was 43.2 and 53.8% were males. Overall, 20 patients (51.3%) experienced at least one significant ADR and 24 reactions were reported in total. Twelve (50%) out of 24 ADRs were severe. The most frequently observed significant ADRs were peripheral sensory neuropathy and CMV reactivation. ADRs led to drug discontinuation for 4 patients and dose reduction for 6 patients. Only 29.2% of the events were spontaneously reported. Prospective monitoring is needed to better assess BV safety.

Long-term treatment of cutaneous manifestations of tuberous sclerosis complex with topical 1% sirolimus cream: A prospective study of 25 patients.

BACKGROUND: Data on long-term topical sirolimus treatment of the cutaneous manifestations of tuberous sclerosis complex are rare. OBJECTIVE: To evaluate the long-term benefit and tolerance of topical 1% sirolimus in tuberous sclerosis complex. METHODS: In this 18-month prospective single-center study, 1% sirolimus cream was applied daily to facial angiofibromas (FAs), fibrous cephalic plaques (FCPs), shagreen patches, hypomelanotic macules, and ungual fibromas. After complete clearance (CC) of FAs, we evaluated a maintenance protocol of 3 applications weekly. RESULTS: Twenty-five patients were enrolled. Fifty percent obtained CC of FAs within 9 months. Of 7 patients with CC (58%) who were following the maintenance protocol, 6 relapsed within 7 months and 1 was still responding at 1 year. Of 16 patients with FCPs, 7 (44%) remained stable at 12 months and 9 (56%) improved after 3 to 9 months of treatment. Only 1 of 5 patients treated for shagreen patches showed improvement at 12 months. Treatment was well tolerated with no serious adverse events. LIMITATIONS: The small number of patients was a limitation. CONCLUSIONS: Topical 1% sirolimus applied daily produced positive responses in treatment of FAs, FCPs, and facial hypomelanotic macules and was well tolerated. A 3-times-weekly maintenance protocol did not prevent FA relapses.

Visual acuity outcome and predictive factors after bevacizumab for central retinal vein occlusion.

PURPOSE: To evaluate the 12-month outcome and predictive factors of visual acuity (VA) changes following bevacizumab therapy for central retinal vein occlusion (CRVO). METHODS: A total of 50 eyes from 50 patients with CRVO were consecutively included in this prospective study. Predictive factors were assessed by comparing baseline characteristics of patients classified into 3 groups: those showing a decrease in VA; those displaying a change in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score between 0 and 15; and those in whom an increase in VA =15 letters was achieved. Baseline variables considered in the analyses of predictive factors were demographic and clinical characteristics. RESULTS: Mean baseline ETDRS letter score was 20±12 and mean macular thickness was 575.1±152.7 µm. Mean final ETDRS letter score improved significantly, reaching 27±20, p=0.04, while mean macular thickness decreased significantly to 391.1±229.6 µm, p<0.001. The predictive factors associated with an increase in VA =15 ETDRS letters were younger age (p=0.002), shorter duration of symptoms before treatment initiation (p=0.001), and a higher visual acuity pretreatment (p=0.004). The frequency of ischemic CRVO and low vision at baseline was higher among nonresponsive patients (p=0.005). CONCLUSIONS: Intravitreal bevacizumab seems to be an effective primary treatment option for macular edema due to CRVO. Its main drawback is that multiple injections are often necessary to maintain visual improvement. Early injections of bevacizumab in young patients in whom VA is relatively preserved leads to a significant improvement in VA. Ischaemic CRVO and poor baseline VA are associated with nonresponse to such therapy.