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This article discusses the effectiveness of hydrolysed rice protein (HRP) formulas in alleviating digestive symptoms in infants with cow's milk protein allergy (CMPA). The study, conducted in France, found that CMPA was the main reason for initiating HRP formulas, followed by digestive disorders and gastroenteritis. The lack of lactose was a common argument for initiating HRP formulas. Parents reported positive and rapid effects of the HRP formulas on digestive symptoms, with a high level of satisfaction. The study was supported by Nutrition Hygiène Santé (NHS), Groupe Menarini. [Extracted from the article]

Introduction: Invasive meningococcal disease (IMD) is still an important cause of mortality in children and survivors can have significant long-term disabling sequelae. There are few prospective studies looking at the long term neuropsychological and developmental consequences of IMD in surviving children, and the rate of sequelae may be underestimated. The SEINE study aims to have a more reliable estimate of the real rate of sequelae by assessing the long-term physical, neuropsychological, learning disorders and sensory sequelae of IMD in children and adolescents and by assessing the post-traumatic stress in parents. Methods and analysis: The SEINE study is a multicentre, prospective, non-randomized, interventional study based on the French bacterial meningitis surveillance network. The study will include 100 children aged from birth to 15 years old, hospitalized in a Paris area paediatric ward for a meningococcal meningitis or a purpura fulminans between 2010 and 2019. The first outcome will assess long-term sequelae (physical, neurological, or sensory) measured by a general clinical and neurological examination, a neurocognitive assessment, learning development, a pure tone audiometry and an ophthalmic examination. The second outcome will assess the long-term post-traumatic stress in parents measured by the Impact of Event Scare Revised questionnaire. Perspectives: By providing a better estimation of the rate of sequelae in children and offering an adapted follow-up of these children, we believe that the SEINE study will help to improve the management of patients surviving IMD. Trial registration number: NCT04685850. [ABSTRACT FROM AUTHOR]

Characteristics of patients at risk of developing severe forms of COVID-19 disease have been widely described, but very few studies describe their evolution through the following waves. Data was collected retrospectively from a prospectively maintained database from a University Hospital in Paris area, over a year corresponding to the first three waves of COVID-19 in France. Evolution of patient characteristics between non-severe and severe cases through the waves was analyzed with a classical multivariate logistic regression along with a complementary Machine-Learning-based analysis using explainability methods. On 1076 hospitalized patients, severe forms concerned 29% (123/429), 31% (66/214) and 18% (79/433) of each wave. Risk factors of the first wave included old age (≥ 70 years), male gender, diabetes and obesity while cardiovascular issues appeared to be a protective factor. Influence of age, gender and comorbidities on the occurrence of severe COVID-19 was less marked in the 3rd wave compared to the first 2, and the interactions between age and comorbidities less important. Typology of hospitalized patients with severe forms evolved rapidly through the waves. This evolution may be due to the changes of hospital practices and the early vaccination campaign targeting the people at high risk such as elderly and patients with comorbidities. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the efficacy of a mix of carboxymethylcellulose and glycerin (Optive®) after intravitreal injection therapy (IVT) with anti-vascular endothelial growth factor for reducing ocular discomfort in patients. Methods: We prospectively included patients who were naïve to any IVT. No artificial tear treatment was prescribed after the first IVT. After the second IVT, all patients instilled 3 drops per day of Optive® for 3 days. Every patient answered a questionnaire concerning the ocular discomfort at 72 h after both IVTs and a questionnaire about tolerance to treatment after the second IVT. Results: We included 45 patients (mean age 72.3 years [range 23–94], 25 females); 14 (34.1%) reported a feeling of grittiness after the first IVT but not after the second (p = 0.01); 12 (29.3%) complained of global discomfort after the first IVT but not after the second (p = 0.14); and 11 (26.8%) reported a watery eye after the first IVT but not after the second (p = 0.21); 37/45 (82%) patients felt ocular discomfort after IVT. Conclusion: Most patients felt ocular discomfort after IVT. Instillation of Optive® significantly alleviated the feeling of grittiness for more than half of the patients. [ABSTRACT FROM AUTHOR]

Among 174 children with blistering distal dactylitis or paronychia, 36.2% had a positive group A Streptococcus (GAS) rapid detection antigen. For GAS, the outcome for patients who received amoxicillin was favorable in all cases without any surgical procedures; 44.6% of cases due to Staphylococcus aureus infection (38.7%) required surgery. [ABSTRACT FROM AUTHOR]

Purpose: Focussing on sickle cell disease (SCD), the objective of this study was to assess adolescents' sexual heath experience in the context of their chronic illness.Materials and Methods: We included teenagers from 14 to 19 years old followed for SCD in a hospital located in Créteil (France) from March 2017 to February 2018. Their sexual health experience was assessed by a self-questionnaire with three key themes: contraceptive experience, awareness of sexuality with chronic disease and level of information on the genetic transmission of the disease.Results: 99 questionnaires were analysed. Only six SCD adolescents (one girl and five boys) reported being sexually active. Despite a very regular follow-up of their illness, only 13% of the boys and girls had received information on contraception at the hospital. Most adolescents (85% of boys and 81% of girls) did not think that the disease would interfere with sexual intercourse. The genetic pattern was well known (85% of boys and 87% of girls).Conclusion: Young people with SCD need more information on contraception. Clinicians caring for them should be aware of the need for sexual health information in order to propose prevention actions adapted to these young people with chronic disease. [ABSTRACT FROM AUTHOR]

Objectives: To assess the management of febrile urinary-tract infection (FUTIs) due to extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) in children, the Pediatric Infectious Diseases Group of the French Pediatric Society set up an active surveillance network in pediatric centers across France in 2014. Materials and methods: We prospectively analysed data from 2014 to 2016 for all children < 18 years old who received antibiotic treatment for FUTI due to ESBL-E in 24 pediatric centers. Baseline demographic, clinical features, microbiological data and antimicrobials prescribed were collected. Results: 301 children were enrolled in this study. The median age was 1 year (IQR 0.02–17.9) and 44.5% were male. These infections occurred in children with history of UTIs (27.3%) and urinary malformations (32.6%). Recent antibiotic use was the main associated factor for FUTIs due to ESBL-E, followed by a previous hospitalization and travel history. Before drug susceptibility testing (DST), third-generation cephalosporins (3GC) PO/IV were the most-prescribed antibiotics (75.5%). Only 13% and 24% of children received amikacine alone for empirical or definitive therapy, respectively, whereas 88.7% of children had isolates susceptible to amikacin. In all, 23.2% of children received carbapenems in empirical and/or definitive therapy. Cotrimoxazole (24.5%), ciprofloxacin (15.6%) and non-orthodox clavulanate–cefixime combination (31.3%) were the most frequently prescribed oral options after obtaining the DST. The time to apyrexia and length of hospital stay did not differ with or without effective empirical therapy. Conclusions: We believe that amikacin should increasingly take on a key role in the choice of definitive therapy of FUTI due to ESBL-E in children by avoiding the use of carbapenems. [ABSTRACT FROM AUTHOR]

Background & Aims: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms. Method: A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations. Results: The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30- 0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03). Conclusions: It is not recommended to genotype the studied polymorphisms in routine practice. [ABSTRACT FROM AUTHOR]

Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer's patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood. In mice infected with Yersinia pseudotuberculosis, we found that PP barrier dysfunction is dependent on the Yersinia virulence plasmid and the expression of TLR-2 by hematopoietic cells, but not by intestinal epithelial cells. Upon TLR-2 stimulation, Y. pseudotuberculosis-infected monocytes activated caspase-1 and produced IL-1β. In turn, IL-1β increased NF-κB and myosin light chain kinase activation in intestinal epithelial cells, thus disrupting the intestinal barrier by opening the tight junctions. Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection. [ABSTRACT FROM AUTHOR]

Complex diseases involve both a genetic component and a response to environmental factors or lifestyle changes. Recently, genome-wide association studies (GWAS) have succeeded in identifying hundreds of polymorphisms that are statistically associated with complex diseases. However, the association is usually weak and none of the associated allelic forms is either necessary or sufficient for the disease occurrence. We argue that this promotes a network view, centred on functional redundancy. We adapted reliability theory to the concerned sub-network, modelled as a parallel array of functional modules. In our model, as long as one module remains active, the function correlated with the respective disease is ensured and disease does not occur. Genetic factors reduce the initial number of available modules while environment, contingent surroundings, personal history, epigenetics, and some intrinsic stochasticity influence their persistence time. This model reproduces age-specific incidence curves and explains the influence of environmental changes. It offers a new paradigm, according to which disease occurs due to a lack of functional elements, depending on many idiosyncratic factors. Genetic risk assessed from GWAS is only a statistical notion with no direct interpretation at the individual level. However, genomic profiling could be useful at population level in devising models to guide decisions in heakh care policy. [ABSTRACT FROM AUTHOR]

The gut-associated lymphoid tissue (GALT) consists of isolated or aggregated lymphoid follicles forming Peyer's patches (PPs). By their ability to transport luminal antigens and bacteria, PPs can be considered as the immune sensors of the intestine. PPs functions like induction of immune tolerance or defense against pathogens result from the complex interplay between immune cells located in the lymphoid follicles and the follicle-associated epithelium. This crosstalk seems to be regulated by pathogen recognition receptors, especially Nod2. Although TLR exerts a limited role in PP homeotasis, Nod2 regulates the number, size, and T-cell composition of PPs, in response to the gut flora. In turn, CD4+ T-cells present in the PP are able to modulate the paracellular and transcellular permeabilities. Two human disorders, Crohn's disease and graft-versus-host disease are thought to be driven by an abnormal response toward the commensal flora. They have been associated with NOD2 mutations and PP dysfunction. [ABSTRACT FROM AUTHOR]

Background: Evidence for the management of pregnant women with acute hypoxaemic respiratory failure (AHRF) is currently lacking. The likelihood of avoiding intubation and the risks of continuing the pregnancy under invasive ventilation remain undetermined. We report the management and outcome of pregnant women with pneumonia related to SARS-CoV-2 admitted to the ICU of tertiary maternity hospitals of the Paris area. Methods: We studied a retrospective cohort of pregnant women admitted to 15 ICUs with AHRF related to SARS-CoV-2 defined by the need for O2 ≥ 6 L/min, high-flow nasal oxygen (HFNO), non-invasive or invasive ventilation. Trajectories were assessed to determine the need for intubation and the possibility of continuing the pregnancy on invasive ventilation. Results: One hundred and seven pregnant women, 34 (IQR: 30–38) years old, at a gestational age of 27 (IQR: 25–30) weeks were included. Obesity was present in 37/107. Intubation was required in 47/107 (44%). Intubation rate according to respiratory support was 14/19 (74%) for standard O2, 17/36 (47%) for non-invasive ventilation and 16/52 (31%) for HFNO. Factors significantly associated with intubation were pulmonary co-infection: adjusted OR: 3.38 (95% CI 1.31–9.21), HFNO: 0.11 (0.02–0.41) and non-invasive ventilation: 0.20 (0.04–0.80). Forty-six (43%) women were delivered during ICU stay, 39/46 (85%) for maternal pulmonary worsening, 41/46 (89%) at a preterm stage. Fourteen non-intubated women were delivered under regional anaesthesia; 9/14 ultimately required emergency intubation. Four different trajectories were identified: 19 women were delivered within 2 days after ICU admission while not intubated (12 required prolonged intubation), 23 women were delivered within 2 days after intubation, in 11 intubated women pregnancy was continued allowing delivery after ICU discharge in 8/11, 54 women were never intubated (53 were delivered after discharge). Timing of delivery after intubation was mainly dictated by gestational age. One maternal death and one foetal death were recorded. Conclusion: In pregnant women with AHRF related to SARS-CoV-2, HFNO and non-invasive mechanical ventilation were associated with a reduced rate of intubation, while pulmonary co-infection was associated with an increased rate. Pregnancy was continued on invasive mechanical ventilation in one-third of intubated women. Study registration retrospectively registered in ClinicalTrials (NCT05193526). [ABSTRACT FROM AUTHOR]

Objectives: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs.Materials and Methods: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed.Results: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54).Conclusions: Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children. [ABSTRACT FROM AUTHOR]

Objectives: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL–producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. Materials and methods: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. Results: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. Conclusions: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin. [ABSTRACT FROM AUTHOR]

Background: The population structure of extraintestinal pathogenic Escherichia coli evolves over time, notably due to the emergence of antibiotic-resistant clones such as ESBL-producing Enterobacteriaceae (ESBL-E).Objectives: To analyse by WGS the genetic diversity of a large number of ESBL-E isolated from urinary tract infections in children from paediatric centres across France between 2014 and 2017 and collected by the National Observatory of febrile urinary tract infection (FUTI) caused by ESBL-E.Methods: A total of 40 905 Enterobacteriaceae-positive urine cultures were identified. ESBL-E were found in 1983 samples (4.85%). WGS was performed on 251 ESBL-E causing FUTI. STs, core genome MLST (cgMLST), serotype, fimH allele, ESBL genes and presence of papGII key virulence factor were determined.Results: E. coli and Klebsiella pneumoniae were found in 86.9% (218/251) and 11.2% (28/251) of cases, respectively. Several STs predominate among E. coli such as ST131, ST38, ST69, ST73, ST95, ST405, ST12 and ST1193, while no ST emerged in K. pneumoniae. E. coli ST131, ST38 and ST1193 increased during the study period, with a heterogeneity in papGII prevalence (64.5%, 35% and 20% respectively). Most isolates harboured the CTX-M type (97%) with a predominance of blaCTX-M-15. blaCTX-M-27, an emerging variant in E. coli, is found in various STs. cgMLST enabled discrimination of clusters within the main STs.Conclusions: The predominance of ST131, and the emergence of other STs such as ST38 and ST1193 combined with ESBL genes deserves close epidemiological surveillance considering their high threat in infectious disease. cgMLST could be a discriminant complementary tool for the analyses. [ABSTRACT FROM AUTHOR]

Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn’s disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn’s disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. [ABSTRACT FROM AUTHOR]

Background Alcohol-related cirrhosis is a frequent and difficult-to-treat disease. Despite the low hepatic metabolism of baclofen, data on its use in this subgroup are scarce. The French multicenter Observatory of patients treated with Baclofen for Alcohol DEpendence real-life cohort assessed: (a) prescription modalities of baclofen in liver units; (b) safety profile of baclofen; and (c) declared alcohol intake, biological markers of excessive alcohol intake and hepatic function at 12 months. Methods All consecutive patients with cirrhosis who received baclofen to reduce alcohol consumption or maintain abstinence were prospectively included. Psychosocial management was always associated. Clinical and biological data were collected every 3 months for 1 year. Results Between November 2013 and December 2016, 71 in- or outpatients were included from 10 liver units. Of the patients, 25% had ascites. After 12 months, 52 patients (73%) were still being followed, and 41 (57.7%) were still receiving baclofen at a mean dosage of 75 mg/day (r30-210). The overall declared consumption decreased from 100.2 to 14.7 g/day (P  < 0.0001), and 29 patients (40.8%) reached abstinence. Significant improvement in the usual biomarkers of excessive alcohol intake (AST, GGT and MCV) and liver function (Prothrombin ratio (PTr), albumin levels) were observed. The usual side effects such as drowsiness were frequent (22%) but no serious adverse events (AEs) or overt encephalopathy related to baclofen was reported. Conclusion In this 1-year follow-up series, baclofen was combined with psychosocial treatment in patients with cirrhosis and was well tolerated. This treatment was associated with a significant decrease in declared alcohol consumption as well as improvement in hepatic function. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances, lung cancer remains the first cause of death from cancer. The main objective of this study was to identify risk factors associated with death within 3- months of the first hospitalization for lung cancer in France. Methods: This analysis included patients with a first hospitalization for lung cancer (between January 1, 2016 and December 31, 2018) according to diagnosisrelated groups entered into the French national medical- administrative database. Clinical and socioeconomic parameters and characteristics of that first hospitalization were analyzed. A model predictive of early mortality was developed based on those variables. Results: The 144,087 included patients were 67% men; median age of 68 [interquartile range 60-76] years; 47% had metastatic disease at diagnosis; and 34% and 23%, respectively, had received systemic treatment or undergone curative surgery. The 3-month mortality was 19%, and significantly higher for those ≥70 versus <70 years old (OR 1.33, 1.22-1.45), men versus. women (OR 1.50, 1.44-1.55), those with metastatic disease at diagnosis (OR, 3.30, 3.18-3.43), first hospitalization via the emergency room (OR 1.65 1.59-1.71) and first hospitalization lasting >30 days (OR, 1.58 1.49-1.68). In contrast, no socioeconomic characteristic was associated with early mortality. Conclusion: Almost 1 in 5 patients diagnosed with lung cancer in France died within 3 months post- diagnosis. Improving survival requires diagnosis at an earlier stage and better organization of diagnosis and specific care pathways. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic rapidly puts a heavy pressure on hospital centers, especially on intensive care units. There was an urgent need for tools to understand typology of COVID-19 patients and identify those most at risk of aggravation during their hospital stay. Data included more than 400 patients hospitalized due to COVID-19 during the first wave in France (spring of 2020) with clinical and biological features. Machine learning and explainability methods were used to construct an aggravation risk score and analyzed feature effects. The model had a robust AUC ROC Score of 81%. Most important features were age, chest CT Severity and biological variables such as CRP, O2 Saturation and Eosinophils. Several features showed strong non-linear effects, especially for CT Severity. Interaction effects were also detected between age and gender as well as age and Eosinophils. Clustering techniques stratified inpatients in three main subgroups (low aggravation risk with no risk factor, medium risk due to their high age, and high risk mainly due to high CT Severity and abnormal biological values). This in-depth analysis determined significantly distinct typologies of inpatients, which facilitated definition of medical protocols to deliver the most appropriate cares for each profile. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate eye rubbing and sleeping position in patients with Unilateral or Highly Asymmetric Keratoconus (UHAKC). Methods: Case-control study of consecutive UHAKC patients diagnosed at the Rothschild Foundation. Controls were age- and sex-matched, randomly selected refractive surgery clinic patients. Patients self-administered questionnaires regarding their family history of keratoconus, eye rubbing, and sleeping habits. All the eyes underwent a comprehensive ocular examination. Logistic regression was used to analyze univariate and multivariate data to identify risk factors for keratoconus. Results: Thirty-three UHAKC patients and 64 controls were included. Univariate analyses showed that daytime eye rubbing [OR = 172.78], in the morning [OR = 24.3], or in eyes with the steepest keratometry [OR = 21.7] were significantly different between groups. Allergy [OR = 2.94], red eyes in the morning [OR = 6.36], and sleeping on stomach/sides [OR = 14.31] or on the same side as the steepest keratometry [OR = 94.72] were also significantly different. The multivariate model also showed statistical significance for most factors including daytime eye rubbing [OR = 134.96], in the morning [OR = 24.86], in the steepest eye [OR = 27.56], and sleeping on stomach/sides [OR = 65.02] or on the steepest side [OR = 144.02]. A univariate analysis in UHAKC group, comparing the worse and better eye, showed that eye rubbing [OR = 162.14] and sleeping position [OR = 99.74] were significantly (p < 0.001) associated with the worse eye. Conclusion: Our data suggests that vigorous eye rubbing and incorrect sleeping position are associated with UHAKC. This is especially true in rubbing the most afflicted eye, and contributory sleep position, including positions placing pressure on the eye with the steepest keratometry. [ABSTRACT FROM AUTHOR]

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS. [ABSTRACT FROM AUTHOR]

To compare stimulated cycle (STC) versus modified natural cycle (MNC) for endometrial preparation prior to frozen embryo transfer (FET) in terms of convenience and efficacy. Prospective, open-label, randomized controlled study including 119 patients aged 20–38 years, undergoing intra-conjugal IVF/intracytoplasmic sperm injection, having regular cycles, at least two day 2 or day 3 frozen embryos, for whom it was the first or second FET performed, randomized to either MNC (n = 59) or STC (n = 60). Monitoring consisted of ultrasound and hormonal measurements. The number of monitoring visits required was compared between the two groups. STC required a significantly lower number of monitoring visits compared with MNC (3.6 ± 0.9 versus 4.4 ± 1.1, respectively, P < 0.0001), a lower number of blood tests (2.7 ± 0.8 versus 3.5 ± 1.0, respectively, P < 0.0001) and of ultrasounds (1.2 ± 0.4 versus 1.5 ± 0.6, respectively, P = 0.0039). FET during 'non-opening' hours (22.6% versus 27.5%, respectively, P = 0.32) and cancellation rates (11.7% versus 11.9%, respectively, P = 0.97) were comparable between the STC and MNC groups. No difference concerning HCG-positive rates (34.0% versus 23.1%, respectively, P = 0.22) nor live birth rates (24.5% for STC versus 23.1% for MNC, respectively, P = 0.86) was observed. Quality of life as defined by the FertiQol score was not different (P > 0.05 for each item). Altogether, these findings can be used for everyday clinical practice to better inform patients when deciding on the protocol to use for FET. These results suggest that MNC is a good option for patients reluctant to have injections, but requires increased monitoring. STC may offer more flexibility for patients and IVF centres. [ABSTRACT FROM AUTHOR]

Importance: Propofol or a combination of a synthetic opioid and muscle relaxant are both recommended for premedication before neonatal intubation but have yet to be compared.Objective: To compare prolonged desaturation during neonatal nasotracheal intubation after premedication with atropine-propofol vs atropine-atracurium-sufentanil treatment.Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial (2012-2016) in 6 NICUs in France that included 173 neonates requiring nonemergency intubation. The study was interrupted due to expired study kits and lack of funding.Interventions: Eighty-nine participants were randomly assigned to the atropine-propofol group and 82 to the atropine-atracurium-sufentanil group before nasotracheal intubation.Main Outcomes and Measures: The primary outcome was prolonged desaturation (Spo2 <80% lasting > 60 seconds), using intention-to-treat analysis using mixed models. Secondary outcomes assessed the characteristics of the procedure and its tolerance.Results: Of 173 neonates randomized (mean gestational age, 30.6 weeks; mean birth weight, 1502 g; 71 girls), 171 (99%) completed the trial. Of 89 infants, 53 (59.6%) in the atropine-propofol group vs 54 of 82 (65.9%) in the atropine-atracurium-sufentanil group achieved the primary outcome (adjusted RD, -6.4; 95% CI, -21.0 to 8.1; P = .38). The atropine-propofol group had a longer mean procedure duration than did the atropine-atracurium-sufentanil group (adjusted RD, 1.7 minutes; 95% CI, 0.1-3.3 minutes; P = .04); a less frequent excellent quality of sedation rate, 51.7% (45 of 87) vs 92.6% (75 of 81; P < .001); a shorter median time to respiratory recovery, 14 minutes (IQR, 8-34 minutes) vs 33 minutes (IQR, 15-56 minutes; P = .002), and shorter median time to limb movement recovery, 18 minutes (IQR, 10-43 minutes) vs 36 minutes (IQR, 19-65 minutes; P = .003). In the 60 minutes after inclusion, Spo2 was preserved significantly better in the atropine-propofol group (time × treatment interaction P  = .02). Of the atropine-propofol group 20.6% had head ultrasound scans that showed worsening intracranial hemorrhaging (any or increased intraventricular hemorrhage) in the 7 days after randomization vs 17.6% in the atropine-atracurium-sufentanil group (adjusted RD, 1.2; 95% CI, -13.1 to 15.5, P = .87). Severe adverse events occurred in 11% of the atropine-propofol group and in 20% of the atropine-atracurium-sufentanil group.Conclusions and Relevance: Among neonates undergoing nonemergency nasotracheal intubation, the frequency of prolonged desaturation did not differ significantly between atropine used with propofol or atropine used with atracurium and sufentanil. However, the study may have been underpowered to detect a clinically important difference, and further research may be warranted.Trial Registration: ClinicalTrials.gov Identifier: NCT01490580, EudraCT number: 2009-014885-25. [ABSTRACT FROM AUTHOR]

Purpose. To compare the qualitative and quantitative choroidal neovascularization (CNV) changes after antivascular endothelial growth factor (anti-VEGF) therapy in treatment-naïve and treated eyes with age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). Methods. Consecutive patients with neovascular AMD underwent multimodal imaging, including OCTA (AngioPlex, CIRRUS HD-OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, OH) at baseline and at three monthly follow-up visits. Treatment-naive AMD patients undergoing anti-VEGF loading phase were included in group A, while treated patients were included in group B. Qualitative and quantitative OCTA analyses were performed on outer retina to choriocapillaris (ORCC) slab. CNV size was measured using a free image analysis software (ImageJ, open-source imaging processing software, 2.0.0). Results. Twenty-five eyes of 25 patients were enrolled in our study (mean age 78.32 ± 6.8 years): 13 treatment-naïve eyes in group A and 12 treated eyes in group B. While qualitative analysis revealed no significant differences from baseline to follow-up in the two groups, quantitative analysis showed in group A a significant decrease in lesion area (P=0.023); in group B, no significant change in the lesion area was observed during anti-VEGF therapy (P=0.93). Conclusion. Treatment-naïve and treated eyes with CNV secondary to neovascular AMD respond differently to anti-VEGF therapy. This should be taken into account when using OCTA for CNV follow-up or planning therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: To assess the anatomical and functional efficacy of ranibizumab on vascularized pigment epithelial detachment (V-PED) secondary to neovascular age-related macular degeneration (nAMD). Methods: One hundred and nine patients (116 eyes) were retrospectively selected from medical records of 2097 patients who benefited from intravitreal injection between January 2011 and June 2013 in a tertiary-care University-based Department of Ophthalmology. Inclusion criteria were: nAMD, treatment-naive eyes, presence of V-PED higher than 250 μm, intravitreal ranibizumab with a loading phase, followed by a pro-re-nata regimen, and 1-year follow-up. Baseline characteristics and type of choroidal neovascularization (CNV) were analyzed. PED height, central macular thickness (CMT) and best-corrected visual acuity (BCVA, logMAR) were measured at baseline, months 3, 6 and 12. Results: CNV was of type 1 in 91 eyes (78.4 %), type 2 in seven (6 %), type 3 in six (5.2 %), and polypoidal choroidal vasculopathy in 12 (10.3 %). Mean CMT at baseline was 572.1 μm and decreased to 396.6 μm ( p < 0.0001) at 12 months. Mean height of PED was 458.2 μm at baseline and 306.8 μm ( p < 0.0001) at 12 months. Mean BCVA improved from 0.46 at baseline to 0.39 at 12 months ( p = 0.013). Conclusions: Treatment with ranibizumab improved visual and anatomical outcome in nAMD patients with V-PED. [ABSTRACT FROM AUTHOR]

Purpose: This work was undertaken to analyze the efficacy of switchback from aflibercept to ranibizumab in patients with neovascular age-related macular degeneration (nAMD) who had previously switched from ranibizumab to aflibercept. Methods: This retrospective double-center study included 45 patients with nAMD who were previously treated with ranibizumab, then aflibercept, and then ranibizumab again, regardless of the number of intravitreal injections received. The primary outcome was change in best-corrected visual acuity (BCVA) measured on the Early Treatment Diabetic Retinopathy Study ETDRS chart before (T0) and after (T1) the switch, and 3 months after the switchback (T2). Secondary outcomes included changes in central foveal thickness (CFT) measured at T0, T1, and T2, as analyzed on spectral-domain optical coherence tomography (SD-OCT), and the percentage of patients gaining five letters or better. Results: Forty-seven eyes of 45 patients were switched back from aflibercept to ranibizumab. The mean BCVA was 67.4 ± 13.4 at T0, 66.7 ± 14.4 at T1, and 68.2 ± 13.9 at T2. BCVA was significantly improved between T1 and T2 ( p = 0.0230), but not between T0 and T1 ( p = 0.5153) or between T0 and T2 ( p = 0.4248). The mean CFT decreased from 317.8 μm ± 89.6 at T0 to 306.9 μm ±68.0 at T1, and to 291.2 μm ± 76.6 at T2. The decrease in CFT was not statistically significant between either T0 and T1 or T1 and T2, but was significant between T0 and T2, when compared before switch and after switchback ( p = 0.0027). However, when considering eyes that received three or more consecutive intravitreal injections of aflibercept before switchback, the statistical significance between T1 and T2 was lost, although a trend towards significance remained ( p = 0.06). Thirteen eyes (27.7 %) gained five letters or more (range, 5-15 letters) after switchback. Conclusions: A short-term benefit of switchback from one anti-VEGF agent to another was observed in patients with nAMD who had shown no benefit from the initial switch. [ABSTRACT FROM AUTHOR]

From 2009 to 2014, we prospectively enrolled 132 children with perianal infections. The presentation of painful defecation, anal fissures, and macroscopic blood in stools was highly suggestive of group A streptococcal perianal infection (probability 83.3%). We found a high sensitivity of a group A streptococcal rapid diagnostic testing (98%) but relatively low specificity (72.8%). [ABSTRACT FROM PUBLISHER]

We evaluated the spectrum of choriocapillaris (CC) abnormalities in the fellow eyes of unilateral exudative age-related macular degeneration (AMD) patients using swept-source optical coherence tomography angiography (SS-OCTA). Fellow eyes of unilateral exudative AMD patients were prospectively included between May 2018 and October 2018. Patients underwent a multimodal imaging including a SS-OCTA. Demographics and clinical findings were analyzed. The estimated prevalence of macular neovascularization (MNV) was computed. Number and size of flow deficits (FDs) and percentage of flow deficits (FD%) were computed on the compensated CC flow images with the Fiji software. We included 97 eyes of 97 patients (mean age was 80 ± 7.66 years, 39 males, 58 females). The prevalence of MNV in the studied eyes was 8.25% (8/97 eyes). In the 89 non-neovascular eyes, FD% averaged 45.84% ± 11.63%, with a corresponding total area of FDs of 4.19 ± 1.12 mm2. There was a higher prevalence of drusenoid pigment epithelial detachment in eyes with subclinical neovascularization (p = 0.021). Fellow eyes with unilateral exudative AMD encompassed a series of CC abnormalities, from FDs of the aging CC to subclinical non-exudative MNV. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the sensitivity and specificity of ultrawide-field fundus photography (UWF-FP) for the detection and classification of sickle cell retinopathy (SCR) by ophthalmologists with varying degrees of expertise in retinal disease. Methods: Patients presenting with sickle cell disease (SCD) in the Créteil University Eye Clinic, having undergone UWF-FP and ultrawide-field fluorescein angiography (UWF-FA) on the same day, were retrospectively included. Eyes with previous retinal photocoagulation were excluded. SCR was graded independently by UWF-FP and UWF-FA using Goldberg classification by two ophthalmologists with varying expertise levels. Results: Sixty-six eyes of 33 patients were included in the study. The sensitivity of UWF-FP for the detection of proliferative SCR was 100%, (95% confidence interval [CI95%] 76.8–100) for the retinal specialist and 100% (CI95% 71.5–100) for the ophthalmology resident. The specificity of UWF-FP for the detection of proliferative SCR was 100% (CI95% 92.7–100) for the retinal specialist and 98.1% (CI95% 89.7–100) for the ophthalmology resident. Conclusions: UWF-FP is a valuable exam for proliferative SCR screening, with excellent sensitivity and specificity and a good inter-grader agreement for ophthalmologists with various degree of skills, and is easy to use in a real-life setting. [ABSTRACT FROM AUTHOR]