Risk factors for laryngeal lesions in adult acute respiratory distress syndrome: A STROBE-compliant French case-control study.

INTRODUCTION: The global SARS-CoV-2 pandemic led to an increased incidence of post-intubation laryngeal injuries in patients with acute respiratory distress syndrome (ARDS). The primary objective of this study was to identify risk factors for symptomatic laryngeal lesions in patients with Covid-19-related ARDS. The secondary objective was to analyze the progression of these laryngeal lesions. METHODS: A 21 month nested case-control study was conducted in 3 university hospital centers of the Hospices Civils de Lyon (France). Cases encompassed all patients intubated for Covid-19-related ARDS who presented symptomatic laryngeal pathology. The control group consisted of all patients enrolled during the same period for Covid-19-related ARDS without evidence of laryngeal lesions (no specific ENT intervention). Uni- and multi-variate analyses were performed to identify risk factors for the occurrence of laryngeal lesions. RESULTS: Forty-nine patients were included in the case group and 50 in the control group. The only significant risk factor for symptomatic laryngeal injury was the number of reintubations, with an odds ratio of 5.08 (95% CI, 1.40-22.12; P=0.013). No other predictive factors were identified among the variables analyzed: obesity, number of prone sessions, self-extubation, duration of intubation and number of days of curarization. CONCLUSION: The number of reintubations was the sole independent risk factor associated with the development of symptomatic laryngeal lesions in patients managed for Covid-19-related ARDS.

ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

BACKGROUND: Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS: This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS: Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION: The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS: This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.

Determination of the optimal dose of ephedrine in the treatment of arterial hypotension due to general anesthesia in neonates and infants below 6 months old: the ephedrine study protocol for a randomized, open-label, controlled, dose escalation trial.

BACKGROUND: Arterial hypotension induced by general anesthesia is commonly identified as a risk factor of morbidity, especially neurological, after cardiac or noncardiac surgery in adults and children. Intraoperative hypotension is observed with sevoflurane anesthesia in children, in particular in neonates, infants younger than 6 months, and preterm babies. Ephedrine is commonly used to treat intraoperative hypotension. It is an attractive therapeutic, due to its dual action on receptors alpha and beta and its possible peripheral intravenous infusion. There are few data in the literature on the use of ephedrine in the context of pediatric anesthesia. The actual recommended dose of ephedrine (0.1 to 0.2 mg/Kg) frequently leads to a therapeutic failure in neonates and infants up to 6 months of age. The use of higher doses would probably lead to a better correction of hypotension in this population. The objective of our project is to determine the optimal dose of ephedrine for the treatment of hypotension after induction of general anesthesia with sevoflurane, in neonates and infants up to 6 months of age. METHODS: The ephedrine study is a prospective, randomized, open-label, controlled, dose-escalation trial. The dose escalation consists of 6 successive cohorts of 20 subjects. The doses studied are 0.6, 0.8, 1, 1.2, and 1.4 mg/kg. The dose chosen as the reference is 0.1 mg/kg, the actual recommended dose. Neonates and infants younger than 6 months, males and females, including preterm babies who undergo a surgery with general anesthesia inducted with sevoflurane were eligible. Parents of the subject were informed. Then, the subjects were randomized if presenting a decrease in mean blood pressure superior to 20% of their initial mean blood pressure (before induction of anesthesia), despite a vascular filling with sodium chloride 0.9%. The primary outcome is the success of the therapy defined as an mBP superior to 80% of the baseline mBP (prior to anesthesia) within 10 min post ephedrine administration. The subjects were followed-up for 3 days postanesthesia. DISCUSSION: This study is the first randomized, controlled trial intending to determine the optimal dose of ephedrine to treat hypotension in neonates and infants below 6 months old. TRIAL REGISTRATION: ClinicalTrials.gov NCT02384876 . Registered on March 2015.

[Focal HIFU vs robot-assisted total prostatectomy: Functionnal and oncologic outcomes at one year]. / Traitement focal par HIFU versus prostatectomie radicale robot-assistée pour cancer de la prostate localisé : résultats carcinologiques et fonctionnels à 1 an.

OBJECTIVE: To analyse the functional and oncologic outcomes at one year of focal therapy with HIFU compared with total prostatectomy in patients with localised prostate cancer (PCa). PATIENTS AND METHODS: Retrospective and monocentric study from 2008 to 2014 comparing 2 cohorts of patients with localised PCa (T1/T2 clinical stage, Gleason score≤3+4=7 and PSA<15ng/mL), one treated by focal therapy (HIFU-F group), one by robot-assisted total prostatectomy (RATP group). Primary outcome was a trifecta defined as: absence of urinary incontinence, erectile function with sexual relations without treatment, negative PSA with negative surgical margins (RATP group) or negative biopsy cores (HIFU-F group). RESULTS: The 53 patients included in the "HIFU-F" group and the 66 patients in the "RATP" group were similar in terms of preoperative PSA, D'Amico risk group, erectile function but were different in terms of age, prostatic volume, length of cancer, Gleason score. Complication rate was not different. In multivariate analyse with propensity score, "HIFU-F" group achieved a better trifecta score than "RATP" group (OR=8,3, p=0,005). CONCLUSION: In case of low or intermediate risk localised PCa, "HIFU-F" group had better functional outcomes than initial learning curse "RATP" group, at one year. A long-term evaluation by a common endpoint is necessary to judge the oncological equivalence of both techniques. LEVEL OF EVIDENCE: 3.

Hospital-acquired infections documented by repeated annual prevalence surveys over 15 years.

OBJECTIVE: To estimate the benefits of iterative prevalence surveys in detecting trends of hospital-acquired infections (HAIs). METHODS: On the basis of the French protocol for national prevalence studies, HAI data of 15 consecutive annual surveys performed at the same period by the same group of investigators was gathered in a single database to describe the trend of HAIs in a University Hospital over a 15-year period. RESULTS: A total of 20,401 patients were included. Overall, the prevalence of patients presenting with at least one HAI acquired in our University Hospital was 5.1% [95% CI, 4.8-5.4%]. The prevalence of HAIs and antimicrobial drug use significantly decreased over time (P<0.01). CONCLUSION: Despite limitations, repeated prevalence surveys can be a useful tool for promoting control measures to better prevent HAIs.

Vancomycin treatment is a risk factor for vancomycin-nonsusceptible Staphylococcus capitis sepsis in preterm neonates.

OBJECTIVES: Multidrug-resistant, vancomycin-nonsusceptible Staphylococcus capitis is an emerging cause worldwide of late-onset sepsis (LOS) in preterm neonates. The pathophysiology and risk factors for S. capitis-related LOS are poorly understood, but we hypothesized that S. capitis LOS follows translocation from the gut microbiota rather than catheter invasion. The objective of this study was to investigate the risk factors of S. capitis LOS and gut colonization. METHODS: We conducted a prospective single-centre cohort study of patients hospitalized in a tertiary-care unit (Lyon, France) from June 2011 to January 2012. S. capitis gut colonization was determined weekly from stool cultures. The determinants of gut colonization and LOS were established by multivariate Cox proportional hazards models. RESULTS: Eighty-three (36.2%) of 229 patients had S. capitis-positive stool culture, and 28 (12.2%) developed S. capitis LOS during hospitalization. Independent risk factors for S. capitis LOS included prior administration of vancomycin independent of a previous LOS episode (hazard ratio 6.44, 95% confidence interval 2.15-19.3, p 0.001) and low birth weight (hazard ratio 0.72 per 100 g increase, 95% confidence interval 0.55-0.95, p 0.02). The prior administration of vancomycin was also an independent risk factor for S. capitis colonization (hazard ratio 3.45, 95% confidence interval 2.07-5.76, p <0.001), particularly in the first week of life and in noncolonized neonates. CONCLUSIONS: Neonates treated with vancomycin are at a higher risk of LOS caused by vancomycin-nonsusceptible S. capitis. The use of vancomycin in neonates must urgently be optimized to limit the selection of vancomycin-nonsusceptible strains, for which alternative antibiotics are lacking.

Cementless lateralized stems in primary THA: Mid-term survival and risk factors for failure in 172 stems.

INTRODUCTION: Increasing the femoral offset when performing total hip arthroplasty (THA) theoretically increases the stresses and risks of the stem not integrating itself into bone. But this concept has not been validated for cementless stems; this led us to conduct a retrospective study to determine: (1) the risk factors for the occurrence of symptomatic femoral radiological abnormalities, (2) the incidence of these abnormal radiological findings, (3) the revision rate for aseptic non-integration of a cementless lateralized stem. HYPOTHESIS: Young patients with significant femoral canal flare and a small cementless lateralized stem have a higher risk of abnormal osseointegration. MATERIAL AND METHODS: We analyzed retrospectively 172 consecutive lateralized stems (KHO, Corail™ product line) implanted during primary THA between 2006 and 2012 in 157 patients (mean age 68years±12.6 (20-95), 89% men). Radiographs were used to evaluate osseointegration scores, offset restoration and the Noble index. Kaplan-Meier survival analysis was performed using "symptomatic femoral radiological abnormalities" and "revision for aseptic stem non-integration" as endpoints. RESULTS: The mean follow-up was 5.9years±2.7 (range, 2-12.4years). Being more than 70years of age (HR=0.7, 95% CI: [0.3-0.9], P=0.004) and having a larger stem (HR=0.6, 95% CI: [0.4-0.9], P=0.03) were protective against symptomatic femoral radiological abnormalities, while increasing the postoperative femoral offset (HR=1.1, 95% CI: [1.01-1.2], P=0.02) was deleterious. The survival free of "symptomatic femoral radiological abnormalities" was 93% (95% CI: 89-97) at 5years and 84% (95% CI: 75-95) at 8years. The survival free of "revision for aseptic stem non-integration" was 98% (95% CI: 96.8-100) at 5years and 97% (95% CI: 95.2-100) at 8years. DISCUSSION: In this study, the risk factors for symptomatic radiological abnormalities were being less than 70years of age, having a small lateralized stem and restoring a large femoral offset. Lateralized stems used in this study had a 10% rate of symptomatic radiological abnormalities and a 4% rate of revision for aseptic non-integration. LEVEL OF EVIDENCE: IV, retrospective study.

[Intra-uterine growth restriction impact on maternal serum concentration of PlGF (placental growth factor): A case control study]. / Impact du retard de croissance intra-utérin sur la concentration sérique maternelle du PlGF (Placental Growth Factor) : une étude cas-témoin.

OBJECTIVES: Placental growth factor (PlGF) is a pro-angiogenic factor mainly assessed in preeclampsia in which its blood concentration is decreased. The aim of this study was to dose the blood concentration of PlGF in women with fetal intra-uterine growth restriction (IUGR) without associated preeclampsia at the time of diagnosis. METHODS: Case/control study: IUGR was defined by a fetal biometry with abnormal uterine and/or umbilical doppler (n=23). This group was compared to a control group of fetuses (n=25) matched for gestational age at blood sampling for the dosage of maternal seric PlGF. Women with preeclampsia were not included. RESULTS: The plasma PlGF concentration was 11pg/mL (IQR [11-42,8]) in the IUGR group vs 287pg/mL [135-439] in the control group (P<0.001) and this difference was available after adjustment for gestational age at the time of blood sampling (P<0.001). PlGF sensitivity and specificity for discrimination were respectively 87% (CI 95% [66-97]) and 88% (CI 95% [69-97]). CONCLUSION: Maternal serum PlGF concentrations were very low in IUGR group compared with those of the control group.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial.

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Robust non-linear mixed modelling of longitudinal PSA levels after prostate cancer treatment.

The objective of this study was to develop a robust non-linear mixed model for prostate-specific antigen (PSA) measurements after a high-intensity focused ultrasound (HIFU) treatment for prostate cancer. The characteristics of these data are the presence of outlying values and non-normal random effects. A numerical study proved that parameter estimates can be biased if these characteristics are not taken into account. The intra-patient variability was described by a Student-t distribution and Dirichlet process priors were assumed for non-normal random effects; a process that limited the bias and provided more efficient parameter estimates than a classical mixed model with normal residuals and random effects. It was applied to the determination of the best dynamic PSA criterion for the diagnosis of prostate cancer recurrence, but could be used in studies that rely on PSA data to improve prognosis or compare treatment efficiencies and also with other longitudinal biomarkers that, such as PSA, present outlying values and non-normal random effects.