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Background: Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data., Methods: We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity., Results: Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall)., Conclusion: Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life., (© 2022. The Author(s).)

Background: Infertility associated with endometriosis can be explained by several non-exclusive mechanisms. The oocyte plays a crucial role in determining embryonic competence and this is particularly relevant for in vitro fertilization (IVF) outcomes. According to some authors, the morphology of oocytes could also be a non-invasive marker of oocyte quality. The aim of this study was to evaluate the relationship between endometriosis and oocyte morphology after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI) on a large oocyte cohort., Methods: Single-center comparative retrospective study in the academic In Vitro Fertilization (IVF) unit of the Lille University Hospital. A total of 596 women treated for IVF-ICSI with ejaculated spermatozoa for sperm alterations were included. They were classified as endometriosis (n = 175) or control groups (n = 401). The morphological evaluation of 2,016 mature oocytes from 348 cycles of patients with endometriosis was compared with that of 4,073 mature oocytes from 576 control cycles. The main outcome measures were Average Oocyte Quality Index (AOQI) and metaphase II oocyte morphological scoring system (MOMS). Comparison of groups was carried out by a mixed linear model and by a generalized estimation equation model with a "patient" random effect to consider that a patient might have several attempts., Results: No difference in AOQI and MOMS scores was found between endometriosis and control women (adjusted p = 0.084 and 0.053, respectively). In case of endometriosis, there were significantly fewer metaphase II oocytes retrieved, embryos obtained, grade 1 embryos and number of cumulative clinical pregnancies compared to controls. In the endometriosis group, endometriosis surgery was associated with a reduced number of mature oocytes retrieved, and the presence of endometrioma(s) was associated with some abnormal oocyte shapes. Nevertheless, no difference concerning the AOQI and MOMS scores was found in these subgroups., Conclusion: Endometriosis does not have a negative impact on oocytes' morphology in IVF-ICSI., Trial Registration: On December 16, 2019, the Institutional Review Board of the Lille University Hospital gave unrestricted approval for the anonymous use of all patients' clinical, hormonal and ultrasound records (reference DEC20150715-0002)., (© 2021. The Author(s).)

Background: With a survival rate of 6 to 11%, out-of-hospital cardiac arrest (OHCA) remains a healthcare challenge with room for improvement in morbidity and mortality. The guidelines emphasize the highest possible quality of cardiopulmonary resuscitation (CPR) and chest compressions (CC). It is essential to minimize CC interruptions, and therefore increase the chest compression fraction (CCF), as this is an independent factor for survival. Survival is significantly and positively correlated with the suitability of CCF targets, CC frequency, CC depth, and brief predefibrillation pause. CC guidance improves adherence to recommendations and allows closer alignment with the CC objectives. The possibility of improving CCF by lengthening the time between two CC relays and the effect of real-time feedback on the quality of the CC must be investigated., Methods: Using a 2 × 2 factorial design in a multicenter randomized trial, two hypotheses will be tested simultaneously: (i) a 4-min relay rhythm improves the CCF (reducing the no-flow time) compared to the currently recommended 2-min relay rate, and (ii) a guiding tool improves the quality of CC. Primary outcomes (i) CCF and (ii) correct compression score will be recorded by a real-time feedback device. Five hundred adult nontraumatic OHCAs will be included over 2 years. Patients will be randomized in a 1:1:1:1 distribution receiving advanced CPR as follows: 2-min blind, 2 min with guidance, 4-min blind, or 4 min with guidance. Secondary outcomes are the depth, frequency, and release of CC; length (care, no-flow, and low-flow); rate of return of spontaneous circulation; characteristics of advanced CPR; survival at hospital admission; survival and neurological state on days 1 and 30 (or intensive care discharge); and dosage of neuron-specific enolase on days 1 and 3., Discussion: This study will contribute to assessing the impact of real-time feedback on CC quality in practical conditions of OHCA resuscitation. It will also provide insight into the feasibility of extending the relay rhythm between two rescuers from the currently recommended 2 to 4 min., Trial Registration: ClinicalTrials.gov, NCT03817892 . Registered on 28 January 2019.

Background: The left ventricular ejection fraction (LVEF) is the key selection criterion for an implanted cardioverter defibrillator (ICD) in primary prevention of sudden cardiac death. LVEF is usually assessed by two-dimensional echocardiography, but cardiovascular magnetic resonance (CMR) imaging is increasingly used. The aim of our study was to evaluate whether LVEF assessment using CMR imaging (CMR-LVEF) or two-dimensional echocardiography (2D echo-LVEF) may predict differently the occurrence of clinical outcomes., Methods: In this retrospective study, we reviewed patients referred for primary prevention ICD implantation to Caen University Hospital from 2005 to 2014. We included 173 patients with either ischemic (n = 120) or dilated cardiomyopathy (n = 53) and who had undergone pre-ICD CMR imaging. The primary composite end point was the time to death from any cause or first appropriate device therapy., Results: The mean CMR-LVEF was significantly lower than the mean 2D echo-LVEF (24% ± 6 vs 28% ± 6, respectively; p < 0.001). CMR-LVEF was a better independent predictive factor for the occurrence of the primary composite endpoint with a cut-off value of 22% (Hazard Ratio [HR] = 2.22; 95% CI [1.34-3.69]; p = 0.002) than 2D echo-LVEF with a cut-off value of 26% (HR = 1.61; 95% CI [0.99-2.61]; p = 0.056). Combination of the presence of scar with CMR-LVEF< 22% improved the predictive value for the occurrence of the primary outcome (HR = 2.58; 95% CI [1.54-4.30]; p < 0.001). The overall survival was higher among patients with CMR-LVEF≥22% than among patients with CMR-LVEF< 22% (p = 0.026), whereas 2D echo-LVEF was not associated with death., Conclusions: CMR-LVEF is better associated with clinical outcomes than 2D echo-LVEF in primary prevention using an ICD. Scar identification further improved the outcome prediction. The combination of CMR imaging and echocardiography should be encouraged in addition to other risk markers to better select patients.

Background: Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival., Methods: From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes., Results: A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1-6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2-5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5., Conclusions: Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Background: Blastocystis sp. is a common protozoan parasite frequently identified in the digestive tract of humans and a large variety of animal hosts worldwide, including birds. It exhibits a large genetic diversity with the identification of 17 subtypes (STs), most of them with low host specificity. ST6 and ST7 were identified in birds and suggested to represent avian STs only in the context of scarce small-scale epidemiological surveys. Moreover, these two STs also account for a significant proportion of human infections whose zoonotic origin has never been clearly confirmed. Therefore, molecular screening of Blastocystis sp. was conducted by quantitative real-time PCR for fecal samples from poultry farms and their in-contact humans from slaughterhouses in Lebanon. In parallel, a control group consisting of patients hospitalized in the same geographical area and reporting no contact with poultry was also screened for the presence of the parasite., Results: The overall prevalence of Blastocystis sp. was shown to reach around 32% in chicken samples and 65% in the farms screened. All the avian isolates were subtyped and belonged to either ST6 or ST7, with a large predominance of ST6. Fifty-four percent of slaughterhouse staff members were positive for Blastocystis sp. compared with a similar prevalence of 56% in hospitalized patients. ST3 was predominant in both human cohorts followed by either ST1 then ST2 among slaughterhouse staff or by ST2 then ST1 among hospitalized patients. ST6 was also identified in two slaughterhouse workers and not in the group of hospitalized patients. Gene sequence identity was observed between chicken and human ST6 isolates from the same slaughterhouse., Conclusions: Our data revealed a high prevalence of Blastocystis sp. in chicken samples and confirmed that ST6 and ST7 represented avian-adapted STs. Among both human cohorts, Blastocystis sp. infection was shown to exceed 50% with a predominance of ST3. The identification of ST6 in slaughterhouse staff members confirmed the zoonotic transmission of this ST through repeated and direct contact between chickens and their handlers.

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. Tranexamic acid (TA), an antifibrinolytic drug, reduces bleeding and transfusion need in major surgery and trauma. In ongoing PPH following vaginal delivery, a high dose of TA decreases PPH volume and duration, as well as maternal morbidity, while early fibrinolysis is inhibited. In a large international trial, a TA single dose reduced mortality due to bleeding but not the hysterectomy rate. TA therapeutic dosages vary from 2.5 to 100 mg/kg and seizures, visual disturbances and nausea are observed with the highest dosages. TA efficiency and optimal dosage in haemorrhagic caesarean section (CS) has not been yet determined. We hypothesise large variations in fibrinolytic activity during haemorrhagic caesarean section needing targeted TA doses for clinical and biological efficacy., Methods/design: The current study proposal is a blinded, randomised controlled trial with the primary objective of determining superiority of either 1 g of TXA or 0.5 g of TXA, in comparison to placebo, in terms of 30% blood-loss reduction at 6 h after non-emergency haemorrhagic caesarean delivery (active PPH > 800 mL) and to correlate this clinical effect in a pharmacokinetics model with fibrinolysis inhibition measured by an innovative direct plasmin measurement regarding plasmatic TA concentration. A sample size of 342 subjects (114 per group) was calculated, based on the expected difference of 30% reduction of blood loss between the placebo group and the low-dose group, out of which 144 patients will be included blindly in the pharmaco-biological substudy. A non-haemorrhagic reference group will include 48 patients in order to give a reference for peak plasmin level., Discussion: TRACES trial is expected to give the first pharmacokinetics data to determinate the optimal dose of tranexamic acid to reduce blood loss and inhibit fibrinolysis in hemorrhagic cesarean section., Trial Registration: ClinicalTrials.gov, ID: NCT02797119 . Registered on 13 June 2016.

Background: Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays., Method/design: The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA]). Patients undergoing H CS (>800 mL) will receive blindly TA 0.5 g or 1 g or placebo. A non-hemorrhagic (NH) group will be recruited to establish plasmin generation profile. Venous blood will be sampled before, at the end, and then at 30, 60, 120, and 360 min after injection. Uterine bleeding will be sampled after injection. Urine will be sampled 2 h and 6 h after injection. The number of patients entered into the study will be 114 H + 48 NH out of the 390 patients of the TRACES clinical trial., Discussion: To explore the two innovative assays, a preliminary pilot study was conducted. Blood samples were performed repeatedly in patients undergoing either a H (>800 mL) or NH (<800 mL) CS and in non-pregnant women (NP). H patients received TA (0-2 g). Dose-dependent TA plasmatic concentrations were determined by LC-MS/MS quantification. Plasmin generation and its inhibition were tested in vitro and in vivo using the simultaneous thrombin-plasmin generation assay (STPGA). The pilot study included 15 patients in the H group, ten patients in the NH group, and seven patients in the NP group. TA plasmatic concentration showed a dose-dependent variation. STPGA inter-assay variation coefficients were < 20% for all plasmin parameters. Inter-individual dispersion of plasmin generation capacity was higher in H and NH groups than in NP group. Profile evolution over time was different between groups. This preliminary technical validation study allows TRACES pharmacobiological trial to be conducted., Trial Registration: ClinicalTrials.gov, NCT02797119. Registered on 13 June 2016.

Background: French Bulldog (FB) has significantly gained in popularity over the last few years, and seems to be frequently affected by various neurological conditions. The purpose of this retrospective study was to report the prevalences of neurological diseases in a large population of FB, presented with neurological signs between 2002 and 2016, and for which a definitive diagnosis was established. A secondary objective was to identify epidemiological characteristics regarding specific diseases in this singular breed., Results: During the study period, 533 FBs were presented for neurological signs, representing 18.7% of all admitted FBs (N = 2846). In total, 343 FBs with definitive diagnosis were included in this descriptive epidemiological study. Hansen type I intervertebral disk herniation (IVDH) was by far the most common neurological disorder (45.5% of all cases). The IVDH location was cervical in 39.8%, and thoracolumbar in 60.2% of cases. The median ages for cervical and thoracolumbar IVDH were 4.2 and 4 years, respectively. C3-C4 was the most commonly affected disk (57.8% of cervical IDVH) all locations combined. Spinal arachnoid diverticulum (SAD) was detected in 25 FBs, representing the second most common myelopathy (11.3%). A concurrent spinal abnormality was identified in 64.0% of SAD cases. Brain tumours represented 36.8% of encephalopathies, with glioma (confirmed or suspected) being the most common. Meningoencephalitis of unknown origin (MUO) represented 25.0% of brain disorders, females less than 5.5 years being more likely to be affected. Aside from central nervous system conditions, otitis interna associated with peripheral vestibular signs and bilateral congenital deafness (associated with white coat) were also common., Conclusions: The findings of this study suggest that FB seems to be prone to several neurological diseases. IVDH is clearly predominant in FB and cervical location seems more represented than in other breeds. FBs affected by IVDH tend to be younger than previously described, either for both cervical and thoracolumbar locations. Thoracic SAD was the second most common myelopathy, with a concurrent spinal anomaly identified in two thirds of the cases. MUO was more likely to affect young to middle-aged females. These findings could be of interest for owners, breeders, practicing veterinarians and insurance companies.

Background: Blastocystis sp. is the most common intestinal parasite of humans. Despite its potential public health impact, epidemiological data regarding the prevalence and molecular subtype distribution of Blastocystis sp. in Europe are rarely reported. Therefore, the first multi-center epidemiological survey performed in Europe was conducted in France to diagnose and subtype Blastocystis sp. and to identify risk factors for infection., Methods: Stool samples from 788 patients were collected either in summer or winter in 11 hospitals throughout France together with patient data. All stool samples were tested for the presence of Blastocystis sp. by quantitative PCR targeting the SSU rDNA gene. Positive samples were sequenced to determine the distribution of the subtypes in our cohort. Statistical analyses were performed to identify potential risk factors for infection., Results: Using quantitative PCR, the overall prevalence of Blastocystis sp. was shown to reach 18.1 %. The prevalence was significantly higher in summer (23.2 %) than in winter (13.7 %). Travellers or subjects infected with other enteric parasites were significantly more infected by Blastocystis sp. than non-travellers or subjects free of other enteric parasites, respectively. Different age-related epidemiological patterns were also highlighted from our data. The prevalence of Blastocystis sp. was not significantly higher in patients with digestive symptoms or diagnosed with chronic bowel diseases. Among symptomatic patients, Blastocystis sp. infection was significantly associated with abdominal pain. Gender, socioeconomic status, and immune status were not identified as potential risk factors associated with infection. Among a total of 141 subtyped isolates, subtype 3 was predominant (43.3 %), followed by subtype 1 and subtype 4 (20 %), subtype 2 (12.8 %), subtype 6 and subtype 7 (2.1 %). No association between ST and clinical symptoms was statistically evidenced., Conclusions: A high prevalence of Blastocystis sp. infection was found in our French patient population. Seasonal impact on the prevalence of Blastocystis sp. was highlighted and recent travels and age were identified as main risk factors for infection. Most cases were caused by subtypes 1 to 4, with a predominance of subtype 3. Large variations in both prevalence and ST distribution between hospitals were also observed, suggesting distinct reservoirs and transmission sources of the parasite.

Background: Contagious Epididymitis (CE) due to Brucella ovis (B. ovis) is a contagious disease that impairs rams' fertility due to epididymis, testicle and accessory sexual gland alterations. An increased incidence of CE has been observed in South Eastern France ("PACA" region) since the Rev.1 vaccination against B. melitensis has been stopped in 2008. The objective of this study was to evaluate the relationship between the infection by B. ovis and the sexual function of rams. Two-hundred eighteen sexually-mature rams, from 11 seropositive flocks, were submitted to a clinical examination of the genital tract, a semen collection by electro-ejaculation for spermogram and culture, and a serological examination for anti-B. ovis antibodies by complement fixation test (CFT) and indirect ELISA (I-ELISA). The relationships between clinical, seminal, bacteriological and serological parameters were studied using the Fisher exact test and a logistic regression model (binomial logit)., Results: B. ovis shedding in semen was significantly associated with seropositivity (CFT and I-ELISA; p < 0.001 and 0.01 respectively), genital tract alterations (p < 0.05) and poor semen quality (p < 0.001). Seropositive rams presented significantly more genital tract alterations (p < 0.001) and a poor seminal score (p < 0.001) than seronegative rams., Conclusions: Since semen culture is not routinely feasible in field conditions, a control plan of CE should be based, where Rev.1 vaccination is not possible, on both systematic clinical and serological examination of rams, followed by the culling of seropositive and/or genital tract alterations carrier rams.

Background: Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk., Methods/design: We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18-year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications., Discussion: This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life., Trial Registration: ClinicalTrial.gov: NCT02046083 (23 January 2014).