Nivolumab in patients with advanced renal cell carcinoma in France: interim results of the observational, real-world WITNESS study.

BACKGROUND: Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452). PATIENTS AND METHODS: This study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here. RESULTS: A total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%. CONCLUSIONS: Preliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.

Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors.

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.

Measles in vulnerable populations: An outbreak in Roma settlements of Loire-Atlantique, France, 2019.

In May 2019, a measles outbreak occurred in the French subregion of Loire-Atlantique, particularly affecting Roma settlements. Various obstacles hindered the implementation of postexposure measures among Roma population, resulting in the spread of the cases to other settlements. Suspected cases of measles were immediately investigated and concerned settlements were visited for measles-mumps-rubella (MMR) vaccination. From July 1 to September 3, 2019, a first and then a second Health Reserve team helped for vaccination on the affected and then also the measles-free settlements. Vaccination uptake was monitored with the use of the department's vaccination center immunization registry. Genotyping of selected samples was performed for comparison with viruses circulating at the same time in France and Romania. As of September 16 2019, 109 cases of measles were confirmed among Roma population, including 99 (91%) children under 15 years. Of the 85 people eligible for vaccination, 60 (71%) had not been vaccinated and 23 (27%) had an unknown vaccination status. Sequence comparison revealed that 28/29 sequenced D8 strains were 100% identical to the strain responsible for a large number of cases throughout France in 2019, and to two sequences reported in Romania among sporadic cases. The vaccination campaign resulted in 1136 people on 35 settlements receiving at least one dose of MMR vaccine and in the increase of one-dose MMR vaccine coverage at 24 months from 43% (23/53) to 91% (48/53). With measles transmission continuing in Europe, efforts must be made to meet immunization coverage targets, particularly in hard-to-reach communities where outbreaks may be difficult to control.

Pediatric pulmonary arterial hypertension due to a novel homozygous GDF2 missense variant affecting BMP9 processing and activity.

Pulmonary arterial hypertension (PAH) is a rare and severe disorder characterized by progressive pulmonary vasculopathy. Growth differentiation factor (GDF)2 encodes the pro-protein bone morphogenetic protein (BMP) 9, activated after cleavage by endoproteases into an active mature form. BMP9, together with BMP10, are high-affinity ligands of activin receptor-like kinase 1 (ALK1) and BMP receptor type II (BMPR2). GDF2 mutations have been reported in idiopathic PAH with most patients being heterozygous carriers although rare homozygous cases have been described. The link between PAH occurrence and BMP9 or 10 expression level is still unclear. In this study, we describe a pediatric case of PAH also presenting with telangiectasias and epistaxis. The patient carries the novel homozygous GDF2 c.946A > G mutation, replacing the first arginine of BMP9's cleavage site (R316) by a glycine. We show that this mutation leads to an absence of circulating mature BMP9 and mature BMP9-10 heterodimers in the patient's plasma although pro-BMP9 is still detected at a similar level as controls. In vitro functional studies further demonstrated that the mutation R316G hampers the correct processing of BMP9, leading to the secretion of inactive pro-BMP9. The heterozygous carriers of the variant were asymptomatic, similarly to previous reports, reinforcing the hypothesis of modifiers preventing/driving PAH development in heterozygous carriers.

[Dysfunction of endothelial BMP-9 signaling in pulmonary vascular disease]. / Dysfonction de la signalisation endothéliale du BMP-9 dans les maladies vasculaires pulmonaires.

The signaling pathway of the bone morphogenetic protein (BMP)-9 binding to the endothelial receptor BMP receptor type II (BMPR-II), activin receptor-like kinase-1 (ALK1) and the coreceptor endoglin is essential to maintain the pulmonary vascular integrity. Dysregulation of this pathway is implicated in numerous vascular diseases, such as pulmonary arterial hypertension (PAH), hereditary hemorrhagic telangiectasia (HHT) and hepatopulmonary syndrome (HPS). This article aims to provide a comprehensive review of the implication of the BMP-9/BMPR-II/ALK1/endoglin pathway in the pathophysiology of these diseases.

[Algorithms to identify chronic inflammatory rheumatism and psoriasis in medico-administrative databases: A review of the literature]. / Algorithmes d'identification des rhumatismes inflammatoires chroniques et du psoriasis dans les bases médico-administratives : revue de la littérature.

BACKGROUND: We aimed to describe and discuss the algorithms used to identify chronic inflammatory rheumatisms and psoriasis in medico-administrative databases. METHODS: We performed a literature review on the Medline database of articles published up to 31 January 2018. Our inclusion criteria were: original articles using medico-administrative databases in accordance with the International Classification of Diseases, version 10 (ICD-10) and concerning rheumatoid arthritis (RA) or ankylosing spondylitis (AS) or psoriatic arthritis (PsoA) or Psoriasis (Pso). Our exclusion criteria were: letters to the editor, commentaries on published articles, studies using codes other than those of the ICD or a previous version. RESULTS: Out of the 590 articles identified, 37 studies were included. Concerning RA (n=10), all studies used the M05 code, associated with the M06 code in six studies. The remaining four studies specifically targeted codes M06.0, M06.2, M06.3, M06.8, M06.9, and two of them also used code M12.3. For AS (n=8), 7 studies used the M45 code, while only one study used M45.9, M46.1 or M46.8. For Pso (n=17), all studies used the L40 code and/or at least two dispensations of vitamin D. Concerning PsoA (n=13), all studies used the same codes: M07.0, M07.1, M07.2, M07.3. CONCLUSION: We recommend using codes M05 and M06 rather than M06.1 and M06.4 for RA, M45 for AS, the algorithm L40 and/or two dispensations of topical vitamin D for psoriasis, and codes M070 to M073 to identify PsoA patients in medico-administrative databases.

[Sleep characteristics of a population of patients seeking bariatric surgery]. / Caractéristiques du sommeil dans une population de patients candidats à une chirurgie bariatrique.

INTRODUCTION: Investigation for obstructive sleep apnea syndrome (OSAS) is mandatory before bariatric surgery. Data regarding chronic insomnia and chronic sleep deprivation are scarce in this population. METHODS: A cross-sectional study assessing the prevalence of chronic insomnia, OSAS and chronic sleep privation in an obese population referred for bariatric surgery. RESULTS: In all, 88 patients (74% women, median age 41 [33.5-50] years and median body mass index 42 [39.2-45.7] kg/m2) were included. The prevalence of chronic insomnia was 31% in the 87% suffering from OSAS that required continuous positive airway pressure therapy. Comorbid insomnia and sleep apnoea (COMISA) were found in 27% of our population. Chronic insomnia was associated with a lower quality of life (median EQ5D analogue visual scale: 60 [50-70] P=0.04) and a poor sleep quality (median Pittsburgh sleep quality index (PSQI): 8 (6-11 P<0.01) The deleterious combination of sleep privation and insomnia had a higher impact in terms of impairment of quality of life and sleep quality (median EQ5D analogue visual scale: 50 [40-65] P=0.02 et median PSQI: 11 [9-14, P<0.01) CONCLUSION: Chronic insomnia and sleep privation have synergistic deleterious effects in candidates for bariatric surgery. Further studies need to be conducted to evaluate the evolution after surgery.

Self-reported sleepiness and not the apnoea hypopnoea index is the best predictor of sleepiness-related accidents in obstructive sleep apnoea.

To evaluate the value of apnoea + hypopnoea index versus self-reported sleepiness at the wheel in anticipating the risk of sleepiness-related accidents in patients referred for obstructive sleep apnoea. A cross-sectional analysis of the French national obstructive sleep apnoea registry. 58,815 subjects referred for a suspicion of obstructive sleep apnoea were investigated by specific items addressing sleepiness at the wheel and sleepiness-related accidents. Apnoea + hypopnoea index was evaluated with a respiratory polygraphy or full polysomnography. Subjects had a median age of 55.6 years [45.3; 64.6], 65% were men, with a median apnoea + hypopnoea index of 22 [8; 39] events/h. Median Epworth sleepiness scale score was 9 [6; 13], 35% of the patients reported sleepiness at the wheel (n = 20,310), 8% (n = 4,588) reported a near-miss accident and 2% (n = 1,313) reported a sleepiness-related accident. Patients reporting sleepiness at the wheel whatever their obstructive sleep apnoea status and severity exhibited a tenfold higher risk of sleepiness-related accidents. In multivariate analysis, other predictors for sleepiness-related accidents were: male gender, ESS, history of previous near-miss accidents, restless leg syndrome/periodic leg movements, complaints of memory dysfunction and nocturnal sweating. Sleep apnoea per se was not an independent contributor. Self-reported sleepiness at the wheel is a better predictor of sleepiness-related traffic accidents than apnoea + hypopnoea index.

Impact of colonization pressure on acquisition of extended-spectrum ß-lactamase-producing Enterobacterales and meticillin-resistant Staphylococcus aureus in two intensive care units: a 19-year retrospective surveillance.

BACKGROUND: Colonization pressure is a risk factor for intensive care unit (ICU)-acquired multi-drug-resistant organisms (MDROs). AIM: To measure the long-term respective impact of colonization pressure on ICU-acquired extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and meticillin-resistant Staphylococcus aureus (MRSA). METHODS: All patients admitted to two ICUs (medical and surgical) between January 1997 and December 2015 were included in this retrospective observational study. Rectal and nasal surveillance cultures were obtained at admission and weekly thereafter. Contact precautions were applied for colonized or infected patients. Colonization pressure was defined as the ratio of the number of MDRO-positive patient-days (PDs) of each MDRO to the total number of PDs. Single-level negative binomial regression models were used to evaluate the incidence of weekly MDRO acquisition. FINDINGS: Among the 23,423 patients included, 2327 (10.0%) and 1422 (6.1%) were colonized with ESBL-PE and MRSA, respectively, including 660 (2.8%) and 351 (1.5%) acquisitions. ESBL-PE acquisition increased from 0.51/1000 patient-exposed days (PEDs) in 1997 to 6.06/1000 PEDs in 2015 (P<0.001). In contrast, MRSA acquisition decreased steadily from 3.75 to 0.08/1000 PEDs (P<0.001). Controlling for period-level covariates, colonization pressure in the previous week was associated with MDRO acquisition for ESBL-PE (P<0.001 and P=0.04 for medical and surgical ICU, respectively), but not for MRSA (P=0.34 and P=0.37 for medical and surgical ICU, respectively). The increase in colonization pressure was significant above 100/1000 PDs for ESBL-PE. CONCLUSION: Colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs.

Long-term adherence to ambulatory initiated continuous positive airway pressure in non-syndromic OSA children.

PURPOSE: In children, the usual indications for continuous positive airway pressure (CPAP) are residual OSA after adenotonsillectomy and/or persistent OSA due to obesity. Data concerning adherence (hours/night) following ambulatory CPAP initiation are scarce. METHODS: An observational cohort of 78 children was followed over 2 years. All exhibited sleep-disordered breathing (SDB) symptoms, were assessed by polysomnography, and prescribed CPAP. CPAP was initiated at hospital for 10 children. RESULTS: OSA children, mean age 10.4 ± 3.2 years, were mostly males (75.6%), with a mean body mass index of 21.2 ± 7.3 kg/m2, and mean apnea+hypopnea index of 12.2 ± 10.6 events/hour. Seventy-two children were still on CPAP at 3 months, 63 at 6 months, 55 at 1 year, and 34 at 2 years. CPAP was discontinued thanks to rehabilitation programs, dento-facial orthopedics, and/or weight loss. Mean CPAP adherence at 1, 3, 6, 12, and 24 months was respectively 6.1 ± 2.8, 6.2 ± 2.6, 6.2 ± 2.8, 6.3 ± 2.8, and 7.0 ± 2.7 h/night. There was a trend towards higher CPAP adherence and younger age, primary versus middle/high school attendance, higher baseline apnea+hypopnea index, and neurocognitive disorders. CONCLUSION: In our population, mean CPAP adherence defined in hours per night was high and did not decrease during the 24-month follow-up. These findings support the feasibility of ambulatory CPAP initiation in non-syndromic OSA. The high CPAP adherence is expected to be associated with improvements in neurocognition, and in metabolic and cardiovascular parameters.

ICU survival and need of renal replacement therapy with respect to AKI duration in critically ill patients.

BACKGROUND: Transient and persistent acute kidney injury (AKI) could share similar physiopathological mechanisms. The objective of our study was to assess prognostic impact of AKI duration on ICU mortality. DESIGN: Retrospective analysis of a prospective database via cause-specific model, with 28-day ICU mortality as primary end point, considering discharge alive as a competing event and taking into account time-dependent nature of renal recovery. Renal recovery was defined as a decrease of at least one KDIGO class compared to the previous day. SETTING: 23 French ICUs. PATIENTS: Patients of a French multicentric observational cohort were included if they suffered from AKI at ICU admission between 1996 and 2015. INTERVENTION: None. RESULTS: A total of 5242 patients were included. Initial severity according to KDIGO creatinine definition was AKI stage 1 for 2458 patients (46.89%), AKI stage 2 for 1181 (22.53%) and AKI stage 3 for 1603 (30.58%). Crude 28-day ICU mortality according to AKI severity was 22.74% (n = 559), 27.69% (n = 327) and 26.26% (n = 421), respectively. Renal recovery was experienced by 3085 patients (58.85%), and its rate was significantly different between AKI severity stages (P < 0.01). Twenty-eight-day ICU mortality was independently lower in patients experiencing renal recovery [CSHR 0.54 (95% CI 0.46-0.63), P < 0.01]. Lastly, RRT requirement was strongly associated with persistent AKI whichever threshold was chosen between day 2 and 7 to delineate transient from persistent AKI. CONCLUSIONS: Short-term renal recovery, according to several definitions, was independently associated with higher mortality and RRT requirement. Moreover, distinction between transient and persistent AKI is consequently a clinically relevant surrogate outcome variable for diagnostic testing in critically ill patients.

Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers.

Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.

Long-term sera storage does not significantly modify the interpretation of toxoplasmosis serologies.

BACKGROUND: Serological investigation of Toxoplasma gondii can answer many questions about toxoplasmosis in human pathology. Along these lines, studies on serum storage in biobanks need to be performed especially in terms of determining the impact of storage on relevance of sera analysis after freezing. This study assessed the impact of long-term sera storage on the stability of anti-Toxoplasma immunoglobulins. MATERIAL AND METHODS: The stability of anti-Toxoplasma IgG and IgM was studied in 244 and 242 sera respectively, stored at -20°C from one month to ten years. ELISA-immunoassay (Vidas®, bioMérieux) was used for initial and post-storage analyses. Linear models for repeated measures and subgroup analyses were performed to assess the effect of storage duration and sample characteristics on immunoglobulins stability. RESULTS: Until ten years, the variability attributed to storage (maximum 8.07% for IgG, 13.17% for IgM) was below the variations inherent to the serological technique and allowed by quality assurance systems (15%). Subgroup analysis reported no variation attributed to sera storage. Serological interpretation was modified for 3 sera (1.2%) tested for IgM, all stored more than seven years. CONCLUSION: Anti-Toxoplasma immunoglobulins can reliably be measured for at least up to six years of storage with no modification of interpretation of toxoplasmosis serologies.

Interpretation of the Elecsys Toxo IgG avidity results for very low and very high index: study on 741 sera with a determined date of toxoplasmosis.

Initial results with the Elecsys Toxo IgG Avidity assay showed some potential for interpretation of a very low or very high index result. We aimed to examine these new insights into interpretation using a large panel of serum samples and to define the optimal thresholds. A total of 741 patient serum samples with known date of infection (from a few weeks to more than 9 months after infection), were analysed with the Elecsys Toxo IgG Avidity assay. Values ≥80% (threshold defined by the manufacturer) were reported in 289 sera; 288 sera were sampled more than 4 months after infection. Thus, avidity values ≥80% excluded an infection less than 4 months. Avidity values ≥90% were reported in 112 sera sampled more than 9 months after infection. Thus, avidity values ≥90% excluded infection less than 9 months. Moreover avidity values ≤15% were reported in the 62 sera sampled less than 3 months after infection. Thus avidity values ≤15% excluded infection more than 3 months.

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units.

OBJECTIVE: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF. RESULTS: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality. CONCLUSIONS: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.

Perioperative docetaxel, cisplatin, and 5-fluorouracil compared to standard chemotherapy for resectable gastroesophageal adenocarcinoma.

BACKGROUND: Even though the perioperative chemotherapy improves the overall survival (OS) compared to surgery alone in patients with a resectable gastroesophageal adenocarcinoma (GEA), prognosis of these patients remains poor. Docetaxel (D), cisplatin (C), and 5-fluorouracil (F) regimen improves OS compared to CF among patients with advanced GEA. We evaluated the potential interest of a perioperative DCF regimen, compared to standard (S) regimens, in resectable GEA patients. METHODS: We identified 459 patients treated with preoperative DCF or S regimens. The primary endpoint was OS. Propensity scores were estimated with a logistic regression model in which all baseline covariates were included. We then used two methods to take PS into account and thus make DCF and S patients comparable. OS analyses were performed with Kaplan-Meier and Cox models in propensity score matched samples, and inverse probability of treatment weighted (IPTW) samples. RESULTS: In the propensity score matched sample, the p-value from the log rank test for OS was 0.0961, and the 3-year OS rate was 73% and 55% in DCF and S groups, respectively. The multivariate Cox regression underlined a Hazard Ratio of 0.55 (95% CI 0.27-1.13) for DCF patients compared to S patients. The results from IPTW analyses showed that DCF was significantly and independently associated with OS (HR = 0.52; 95% CI 0.40-0.69). CONCLUSIONS: In this retrospective multicenter, hypothesis-generating study, the propensity score analyses underlined encouraging results in favor of DCF compared to S regimens regarding OS. This promising result should be validated in a phase-3 trial.

Impact of systemic antifungal therapy on the detection of Candida species in blood cultures in clinical cases of candidemia.

The diagnosis and follow-up of candidemia still rely on blood cultures (BCs). In vitro studies show that antifungals can significantly modify the result of blood culture not containing adsorbing agents. We aimed to evaluate, under clinical conditions, the impact on BC yeast detection of systemic antifungal therapy (SAT). Patients (n = 125) experiencing candidemia at Grenoble University Hospital (France) were included in a 4-year retrospective study. The Plus Aerobic/F (Aerobic) and Plus Anaerobic/F (Anaerobic) bottles, which both contain adsorbing resins and the non-resin selective Mycosis IC/F (Mycosis) bottles, were compared using multivariate hierarchical models adjusted for clinical characteristics. The positivity rate (PR) is decreased in patients with SAT (p < 0.01), abdominal surgery (p = 0.01), and hemodialysis (p = 0.02). In all bottles, SAT reduces PR by a factor of 0.16 (95 % CI: [0.08; 0.32]) and increases the time to positivity (TTP) by a factor of 1.76 ([1.30; 2.40]; p < 0.01). In the presence of SAT, TTP is higher in non-resin bottles (Mycosis) than in resin bottles (RR = 1.76, [1.30; 2.40]); however, the TTP in nonresin and resin bottles remains comparable. Although discordant results are observed with and without SAT (37 and 58 % respectively), we showed that the presence of SAT decreases significantly the agreement rate by a factor of 0.29 (CI: [0.12; 0.68]). The combination of Anaerobic and Mycosis bottles allowed a 100 % positivity rate for C. glabrata. SAT significantly affects BC results. Because they provide additional and complementary results, this study supports the concomitant use of resin and selective bottles, especially in patients receiving SAT.