Search

Abstract Background Respiratory syncytial virus (RSV) is the most frequently identified pathogen in children with acute lower respiratory tract infection. Fatal cases have mainly been reported during the first 6 months of life or in the presence of comorbidity. Case presentation A 47-month-old girl was admitted to the pediatric intensive care unit following sudden cardiopulmonary arrest occurring at home. The electrocardiogram showed cardiac asystole, which was refractory to prolonged resuscitation efforts. Postmortem analyses detected RSV by polymerase chain reaction in an abundant, exudative pericardial effusion. Histopathological examination was consistent with viral myoepicarditis, including an inflammatory process affecting cardiac nerves and ganglia. Molecular analysis of sudden unexplained death genes identified a heterozygous mutation in myosin light chain 2, which was also found in two other healthy members of the family. Additional expert interpretation of the cardiac histology confirmed the absence of arrhythmogenic right ventricular dysplasia or hypertrophic cardiomyopathy. Conclusions RSV-related sudden death in a normally developing child of this age is exceptional. This case highlights the risk of extrapulmonary manifestations associated with this infection, particularly arrhythmia induced by inflammatory phenomena affecting the cardiac autonomic nervous system. The role of the mutation in this context is uncertain, and it is therefore necessary to continue to assess how this pathogenic variant contributes to unexpected sudden death in childhood.

Visceral leishmaniasis is an enzootic parasitosis present across the Mediterranean Basin. Some consider it an opportunistic parasite. We report the case of a girl treated with anti-tumour necrosis factor alpha (anti-TNFα) for juvenile idiopathic arthritis who had previously presented with visceral leishmaniasis. Two and a half years later, she presented a tumour-like mass in the nasal mucous membrane caused by Leishmania parasites. Leishmania infantum is classically responsible for visceral leishmaniasis, but pure mucocutaneous leishmaniasis has also been described. To our knowledge, this is the first observation of a recurrence of visceral leishmaniasis in the mucocutaneous form. The occurrence of atypical forms and presentations in those on anti-TNF therapy should be considered.

Purpose: The Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI) and the Italian Association of Medical Physics (AIFM) offer a certified audit service to radiotherapy (RT) centers for reference dosimetry., Methods: Audits are provided for photon beams in the range 6-18 MV including flattening filter free C-arm Linac, CyberKnife and TomoTherapy beams. A dosimeter consisting of a set of TLD chips embedded in a PMMA waterproof holder is used. TLDs are calibrated in terms of absorbed dose to water in the ENEA-INMRI reference 60 Co γ-beam. Correction factors accounting for energy dependence, signal reproducibility and response stability are applied to evaluate absorbed dose. For each beam audited, irradiation of two dosimeters with 2 Gy is required in reference conditions, according to the international dosimetry protocols. Audit performance is evaluated in terms of theE n score: it is satisfactory if |E n | ≤ 1.0., Results: Audit was successfully performed for 94beams in 34 ItalianRTcenters. Nominal beam energies analysed were 6 MV (38.3 %), 6 MV FFF (33.0 %), 10 MV (12.8 %), 10 MV FFF (4.2 %), 15 MV (9.6 %) and 18 MV (2.1 %). TheE n scores are normally distributed with 95 % of data between -0.54 and 0.7; 99.5 % of values are in the range [-1.0,1.0] and 81.1 % are in the optimal range [-0.5,0.5]. As for the single unsatisfactory result, data from the form filled in by the RT center allowed ENEA-INMRI to identify an error in the measurement setup., Conclusions: Results of remote audits have shown excellent performance of Italian RT centers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background/Objectives : The aim of the study was to compare dacryocystectomy (DCT) versus dacryocystorhinostomy (DCR) in patients with dacryocystitis in terms of tearing complaints. Methods : We conducted a retrospective and comparative study on 19 patients. The main outcome measure was defined as an improvement by 1 point of the Munk score postoperatively. Results : A total of 19 patients were included with 10 in the DCR group and 9 in the DCT group. The primary endpoint was reached in 7 (70%) and in 6 (67%) patients in the DCR and DCT groups, respectively ( p > 0.999). All DCR procedures were performed under general anesthesia (GA), while almost all DCT procedures were performed under local anesthesia (LA) ( p < 0.001). There was a higher need for hospitalization in the DCR group ( p < 0.001). Conclusions : Our preliminary results indicate that DCR is not always the solution in the case of dacryocystitis. DCT is a viable surgical procedure, especially in elderly patients without any tearing complaint and with underlying dry eye disease.

Purpose: Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients' genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France., Methods: A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed., Results: In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A two-by-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87)., Conclusions: We described a genotype-phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA.

Although retinoids are considered as the most effective treatment, management of dissecting cellulitis of the scalp (DCS) is often challenging. A multicentre retrospective study was conducted to evaluate the efficacy of anti-tumour necrosis factor (TNF) agents in treating DCS after failure of other conventional treatments. Twenty-six patients were included. After a mean treatment duration of 19 months (SD 21), the median Physician's Global Assessment score decreased from 3 to 1. The median number of inflammatory nodules and abscesses decreased from 7 to 0.5 and from 1 to 0, respectively. The median Dermatology Life Quality Index and numerical rating scale score for pain severity decreased from 10 to 8 and 6 to 1, respectively. The median treatment satisfaction was 7 out of 10 on the Patient Satisfaction Index. This study confirms the efficacy of anti-TNF agents in treating patients with DCS that is resistant to conventional therapies., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations in at least 20 different genes have been identified. Oculo-cutaneous Albinism type IV (OCA4) is the most frequent form in Asia but has been reported in all populations, including Europeans. Little is known about the genotype-phenotype correlation. We identified two main phenotypes via the analysis of 30 OCA4 patients with a molecularly proven diagnosis. The first, found in 20 patients, is clinically indistinguishable from the classical OCA1 phenotype. The genotype-to-phenotype correlation suggests that this phenotype is associated with homozygous or compound heterozygous nonsense or deletion variants with frameshift leading to translation interruption in the SLC45A2 gene. The second phenotype, found in 10 patients, is characterized by very mild hypopigmentation of the hair (light brown or even dark hair) and skin that is similar to the general population. In this group, visual acuity is variable, but it can be subnormal, foveal hypoplasia can be low grade or even normal, and nystagmus may be lacking. These mild to moderate phenotypes are associated with at least one missense mutation in SLC45A2 .

Background: Pyoderma gangrenosum is a scarce ulcerating inflammatory skin disease, which requires excluding other causes of ulceration such as infections, malignancies or connective tissue diseases. Case Report: We report the case of a 38-year-old woman who developed a progressive bilateral breast skin ulcer after breast plastic surgery, suspected initially with an early postoperative infection. The lack of improvement despite adequate antimicrobial drugs conducted to perform a skin biopsy, concluding to an ulcerated neutrophil dermatosis which led to the diagnosis of postoperative pyoderma gangrenosum . The clinical course was favorable with a systemic treatment based on steroids. Conclusions: In order to prevent debridement and extension of local complications, this case report illustrates the importance to suspect pyoderma gangrenosum as differential diagnosis of infection after surgery.

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient's behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides . Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.

Introduction: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival., Material and Methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis., Results: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group., Conclusion: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up., Methods: We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected., Results: A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections., Conclusions: The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses., (© 2021. The Author(s).)

Background: The aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC., Methods: All p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS)., Results: 382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis., Conclusion: In p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background & Aims: Chronic alcohol consumption can cause malnutrition that may contribute to alcohol-induced organ injury and psychological disorders. We evaluated the link between nutrient intake, especially dietary fibers (DF) and different parameters reflecting mental health and well being, namely anxiety, depression, alcohol craving, sociability, fatigue and intestinal comfort in alcohol use disorder (AUD) patients., Methods: Cross-sectional data from 50 AUD patients, hospitalized for a 3-week detoxification program were used. Three 24-h recalls allowed to calculate dietary habits and nutrient intakes, that was also assessed in healthy subjects (HS). Diet quality was measured using the NOVA score. Psychological factors and intestinal discomfort were evaluated using validated self-administered questionnaires., Results: Energy intake (excluding alcoholic beverage), total fat, monounsaturated and polyunsaturated fatty acids, protein and DF intakes were lower in AUD subjects compared to HS. Ninety percent of patients had a DF intake below the recommendation. AUD patients consumed more than twice as much ultra-processed food than HS. Fructan intake was negatively associated with anxiety (p = 0.04) adjusted for main confounders. Total DF, insoluble, soluble DF and galacto-oligosaccharide intakes were associated with higher sociability score. Soluble DF intake was associated with better satisfaction of bowel function (p = 0.02) and a lower intestinal discomfort (p = 0.04)., Conclusions: This study reveals that insufficient DF intake is part of AUD-related malnutrition syndrome, and is associated with higher anxiety, lower sociability score and intestinal discomfort. Our results suggest that an adequate intake of DF might be beneficial for recovery from AUD., Trial Registration: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709., Competing Interests: Conflicts of interest The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hermansky-Pudlak syndrome (HPS) is a rare form of syndromic oculocutaneous albinism caused by disorders in lysosome-related organelles. Ten genes are associated with different forms of HPS. HPS type 9 (HPS-9) is caused by biallelic variants of BLOC1S6 . To date, only three patients with HPS-9 have been reported. We described one patient presenting with ocular features of albinism. Genetic analysis revealed two compound heterozygous variants in the BLOC1S6 gene. Extended hematological studies confirmed the platelet storage pool disease with absence of dense granules and abnormal platelet aggregation. By reviewing the previous published cases we confirm the phenotype of HPS-9 patients. This patient is the only one described with dextrocardia and abnormal psychomotor development.

Purpose: To evaluate long terms outcomes of botulinum toxin in infantile esotropia by measuring the amount of microtropia 24 months after injection. Secondary purpose was to identify predictive factors of microtropia., Methods: A retrospective, single-center study was performed at the university medical center in Bordeaux between 2001 and 2018, including all patients with infantile esotropia greater than 20 D. All patients received 5 or 7,5 IU of botulinum toxin A in each medial rectus, once or twice depending on the angle of deviation after the first injection and after wearing full optical correction at least two months. We noted the angle at 1, 6, 12 and 24 months, the occurrence of any complications and the need for later strabismus surgery. The primary endpoint was the achievement of a microtropia less than 8 diopters (D) at 24 months post-injection. We evaluated the predictive factors for microtropia with a Fischer's test., Results: We included 30 patients with esotropia greater than 20 D. The mean follow-up after injection was 48 months ±30. The mean age was 16.24 months (7-29 months) with a female predominance in the population (SR=0.43). The mean pre-injection deviation was 41.25±12.17 D. The majority of patients were mildly (40%) or moderately (40%) hyperopic. At 24 months, 46.7% microtropias were obtained (95% CI: 28.9%-64.5%). The change in mean angle at 1, 6, 12 and 24 months post-injection was -8.57±25.21 D; 14.48±13.40 D; 18.38±12.07 D and 21.23±14.97 D, respectively. No factors were predictive of microtropia. Of the 30 children, 3 had transient ptosis requiring strips and 12 showed an exotropia at 1 month. All complications were self-limited and without consequences. 3 children had a second injection of botulinum toxin, which in 2/3 of the cases resulted in a long-lasting microtropia. 26.7% (n=8) of the children underwent secondary surgery. Obtaining a microtropia 24 months after injection statistically significantly reduced the need for secondary strabismus surgery: 92.9% P=0.039% CI 95% (0.002; 1.0606)., Conclusion: Botulinum toxin appears to be a less invasive and more conservative alternative to surgery in children with infantile esotropia. In 46.7% of cases, microtropia is achieved. An improvement was noted in 90% (n=27) of the children with a reduction of half (21.23 D) of the mean post-injection angle at 24 months. When effective, it significantly reduces the need for secondary surgery., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Therapeutic management of oropharyngeal squamous cell carcinomas (OPSCC) is still debated. Since the role of HPV was demonstrated, few studies have focused on HPV-negative OPSCC. The aim of our study was to assess the impact of therapeutic strategy (surgical vs. non-surgical) on oncologic outcomes in patients with HPV-negative OPSCC., Material and Method: All p16-negative OPSCCs treated from 2009 to 2014 in 7 tertiary-care centers were included in this retrospective study and were classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Patients not eligible for surgery (unresectable tumor, poor general-health status) were excluded. Univariate, multivariate and propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS)., Results: Four hundred seventy-four (474) patients were included in the study (surgical group: 196; non-surgical group: 278). Five-year OS, DSS and RFS were 76.5, 81.3 and 61.3%, respectively, in the surgical group and 49.9, 61.8 and 43.4%, respectively, in the non-surgical group. The favorable impact of primary surgical treatment on oncologic outcomes was statistically significant after multivariate analysis. This effect was more marked for locally-advanced than for early-stage tumors. Propensity score matching analysis confirmed the prognostic impact of primary surgical treatment for RFS., Conclusion: Therapeutic strategy is an independent prognostic factor in patients with p16-negative OPSCC and primary surgical treatment is associated with improved OS, DSS and RFS. These results suggest that surgical strategy is a reliable option for advanced stage OPSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk of synchronous primary neoplasia (SPN) which could impact their management. The aims of this study were to evaluate the risk and distribution of SPN in OPSCC patients according to their HPV (p16) status, the predictive factors of SPN and the impact of SPN on therapeutic strategy and oncologic outcomes., Material and Methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. Univariate analyses were conducted using Chi-2 and Fisher exact tests. For multivariate analyses, all variables associated with a p ≤ 0.10 in univariate analysis were included in logistic regression models., Results: Among the 1291 patients included in this study, 75 (5.8%) displayed a SPN which was preferentially located in the upper aerodigestive tract, lung and esophagus. Comorbidity level (p = 0.03), alcohol (p = 0.005) and tobacco (p = 0.01) consumptions, and p16 tumor status (p < 0.0001) were significant predictors of SPN. In multivariate analysis, p16+ status was significantly associated with a lower risk of SPN (OR = 0.251, IC95% [0.133;0.474]). Patients with a SPN were more frequently referred for non-curative treatment (p = 0.02). In patients treated with curative intent, there was no impact of SPN on the therapeutic strategy (surgical vs. non-surgical treatment). We observed no overall survival differences between patients with or without SPN., Conclusion: P16 tumor status is the main predictive factor of SPN in OPSCC patients. This study provides crucial results which should help adapt the initial work-up and the global management of OPSCC patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Although Human Papilloma Virus (HPV)-driven oropharyngeal cancer (OPC) prognosis is significantly better than that of other head and neck cancers, up to 25% of cases will recur within 5 years. Data on the pattern of disease recurrence and efficiency of salvage treatment are still sparse., Material and Method: Observational study of all recurrent OPCs diagnosed, following a curative intent treatment, in seven French centers from 2009 to 2014. p16 Immunohistochemistry was used to determine HPV status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival was examined using Kaplan-Meier and multivariate Cox regression modeling., Results: 350 recurrent OPC patients (246 p16-negative and 104 p16-positive patients). The site of recurrence was more frequently locoregional for p16-negative patients (65.4% versus 52.9% in p16-positive patients) and metastatic for p16-positive patients (47.1% versus 34.6% in p16-patients, p = 0.03). Time from diagnosis to recurrence did not differ between p16-positive and p16-negative patients (12 and 9.6 months, respectively, p-value = 0.2), as the main site of distant metastasis (all p-values ≥0.10). Overall and relapse-free survival following the first recurrence did not differ according to p16 status (p-values from log-rank 0.30 and 0.40, respectively). In multivariate analysis, prognosis factors for overall survival in p16-negative patients were distant metastasis (HR 2.11, 95% CI 1.30-3.43) and concurrent local and regional recurrences (HR 2.20, 95% CI 1.24-3.88)., Conclusion: With the exception of the initial site of recurrence, the pattern of disease relapse and the efficiency of salvage treatment are not different between p16-positive and negative OPCs., Competing Interests: Conflict of interest statement All the authors do not have conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: 12b80 combines doxorubicin bound to a bone targeting hydroxybisphosphonate vector using a pH-sensitive linker, designed to specifically trigger doxorubicin release in an acidic bone tumor microenvironment. This phase I study aimed to determine the safety and toxicity profiles of 12b80 in dogs with naturally occurring osteosarcoma, with the objective to translate findings from dogs to humans., Experimental Design: Ten client-owned dogs with osteosarcoma were enrolled in an accelerated dose-titration design followed by 3 + 3 design. Dogs received three cycles of 12b80 intravenous injection at 4 mg/kg ( n = 1), 6 mg/kg ( n = 2), 8 mg/kg ( n = 3), and 10 mg/kg ( n = 4). Endpoints included safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity (DLT)., Results: The MTD of 12b80 was 8 mg/kg (i.e., equivalent dose of doxorubicin of 110 mg/m 2 , range: 93-126). Most adverse events included grade ≤ 2 gastrointestinal disorders and hypersensitivity reactions. No hematological or cardiac DLT were observed at any dose tested., Conclusions: In dogs, 12b80 is overall well tolerated and expends the MTD of doxorubicin up to four times the standard dose of 30 mg/m 2 . These results demonstrate the potential therapeutic benefit of 12b80 in canine and human osteosarcoma., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare., (Copyright: © 2020 Boyé et al.)

Patients with alcohol use disorder (AUD) present with important emotional, cognitive, and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show that gut dysbiosis is associated with metabolic alterations that affect behavioral (depression, sociability) and neurobiological (myelination, neurotransmission, inflammation) processes involved in alcohol addiction. By transplanting the gut microbiota from AUD patients to mice, we point out that the production of ethanol by specific bacterial genera and the reduction of lipolysis are associated with a lower hepatic synthesis of β-hydroxybutyrate (BHB), which thereby prevents the neuroprotective effect of BHB. We confirm these results in detoxified AUD patients, in which we observe a persisting ethanol production in the feces as well as correlations among low plasma BHB levels and social impairments, depression, or brain white matter alterations., Competing Interests: Declaration of Interests P.D.C. is the inventor of patent applications dealing with the use of A. muciniphila and its components in the context of obesity and related disorders. P.D.C. is co-founder of A-Mansia Biotech SA. The other authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Management of Graves' ophthalmopathy remains challenging. Over the last decade, previous studies have shown promising results for Rituximab in the treatment of Graves' ophthalmopathy. We present the response of 14 individuals with active moderate-to-severe Graves' ophthalmopathy to Rituximab, representing one of the largest retrospective case series reported to date., Methods: Rituximab was administered intravenously, 1000 mg twice at a 2-week interval. The primary end point was a clinical activity score reduction (improvement by ⩾ 2 points or disease inactivation: clinical activity score < 3) at 24 weeks. Secondary end points included clinical activity score improved by ⩾ 2 points or inactivation of Graves' ophthalmopathy at 12 weeks, improvement in each item of the clinical activity score, in proptosis, in severity disease by the total eye score and in diplopia according to the Gorman score., Results: A limited improvement in clinical activity score was observed (median improvement at 24 weeks by 1 point, p = 0.002, (5/14 patients, 35.7%). Disease inactivation occurred in 50% of patients (7/14 patients). At 12 weeks, clinical activity score improved by ⩾ 2 points in 2/14 patients (14.3%) and inactivation of Graves' ophthalmopathy occurred in four patients (28.6%). Improvement in proptosis and total eye score was observed in 3/9 patients (33%) and in 4/14 patients (28.6%) at 24 weeks, respectively. Only one patient experienced moderate adverse event., Conclusion: Rituximab is a well-tolerated treatment with a good safety profile, but offered limited and partial improvement for active moderate-to-severe Graves' ophthalmopathy with a long duration of disease.

Purpose: F14512 is an epipodophyllotoxin derivative from etoposide, combined with a spermine moiety introduced as a cell delivery vector. The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma (NHL) and to investigate the potential benefit of F14512 in P-glycoprotein (Pgp) overexpressing lymphomas. Experimental Design: Forty-eight client-owned dogs with intermediate to high-grade NHL were enrolled into a randomized, double-blind trial of F14512 versus etoposide phosphate. Endpoints included safety and therapeutic efficacy. Results: Twenty-five dogs were randomized to receive F14512 and 23 dogs to receive etoposide phosphate. All adverse events (AEs) were reversible, and no treatment-related death was reported. Hematologic AEs were more severe with F14512 and gastrointestinal AEs were more frequent with etoposide phosphate. F14512 exhibited similar response rate and progression-free survival (PFS) as etoposide phosphate in the global treated population. Subgroup analysis of dogs with Pgp-overexpressing NHL showed a significant improvement in PFS in dogs treated with F14512 compared with etoposide phosphate. Conclusion: F14512 showed strong therapeutic efficacy against spontaneous NHL and exhibited a clinical benefice in Pgp-overexpressing lymphoma superior to etoposide phosphate. The results clearly justify the evaluation of F14512 in human clinical trials., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest., (Copyright: © 2020 Boyé et al.)

Purpose: To evaluate the medical-surgical management of cataract surgery in children with chronic uveitis in various French pediatric ophthalmology centers., Materials and Methods: Two-part study: first, a descriptive observational segment on the evaluation of French practices. A questionnaire was sent to the various pediatric ophthalmologists in France. A second retrospective chart review, including children with non-infectious chronic uveitis who had cataract surgery in the pediatric ophthalmology department of Bordeaux University Hospital from 2008 to 2017., Results: Twenty-one ophthalmologists responded to the questionnaire. Only 23.8% systematically initiated immunosuppressive drugs (aside from corticosteroids) before surgery. A total of 88.2% prescribed oral corticosteroid treatment preoperatively. Eleven surgeons administered intravenous corticosteroid boluses during the surgery, and primary lens implantation is the most common method used in 95.2%. A total of 76.2% initiated oral steroid therapy after surgery. Postoperatively, all surgeons started local therapy with high-dose corticosteroids. At one year, 100% achieved improvement of visual acuity greater than or equal to 2 lines. On our service, 10 eyes (7 children) underwent cataract surgery. Seven were treated with systemic immunosuppressive drugs (aside from corticosteroids) and 80% of cases received oral corticosteroid therapy a few days before surgery. An intravenous corticosteroid bolus was administered preoperatively in 8 cases, and primary lens implantation was performed in 100% of cases. Postoperatively, 5 children received oral corticosteroid treatment. All were treated with local high dose steroids. At one year, the mean best-corrected visual acuity was 0.18 LogMar (0-0.7, SD: 0.25)., Conclusion: When performed with an aggressive anti-inflammatory protocol, cataract surgery leads to a good visual outcome in selected children with chronic uveitis., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: To analyze the prevalence and risk factors for retinopathy of prematurity (ROP) and severe (treatment-requiring) ROP., Methods: A retrospective study was conducted in a level III neonatal unit in Bordeaux, France, from 2009 to 2015. Four hundred and nineteen preterm infants who were screened for ROP exclusively by RetCam were included., Results: ROP of any degree was diagnosed in 27.68% of infants. Stages 1, 2, 3 and 4 ROP was found in 44%, 46%, 9% and 1% of subjects, respectively. No stage 5 ROP was observed. 28/419 infants (6.6%) were treated exclusively with laser photocoagulation. No intravitreal anti-VEGF injections or surgical treatments were performed. No infants born at>31 weeks or with BW>1110g required ROP treatment. On multivariate analysis, risk factors for ROP development were low birth weight, low gestational age at birth, high duration of invasive mechanical ventilation, shock or use of vasopressors. On multivariate analysis, risk factors for severe, treatment-requiring ROP were male gender, gestational age≤27 weeks and Apgar score at 5minutes≤7., Conclusion: In our 6-year series, ROP was successfully identified on screening exclusively by telemedicine, and no surgical treatment was required. This study identifies known ROP risk factors, but the Apgar score at 5minutes as a risk factor for severe ROP requires further studies in order to be confirmed., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Albinism is a rare genetic disease, comprising syndromic and non-syndromic forms. We assessed clinical and genetic characteristics in a prospective evaluation of 64 patients (33 children and 31 adults) seen at a specialized day hospital. Causative genetic mutations were found in TYR (23/64, 35.9%), OCA2 (19/64, 29.7%), TYRP1 (1/64, 1.6%), SLC45A2 (12/64, 18.7%), C10orf11 (1/64, 1.6%), HPS1 (3/64, 4.7%), HPS5 (1/64, 1.5%), HPS6 (1/64, 1.6%) and GPR143 (2/64, 3.1%). Causative mutations remained undetermined for one patient (1.6%). Heterogeneity for hair and skin phenotype was noted across and within the different genotypes. Skin and hair hypopigmentation did not correlate with visual impairment. The diagnosis of unrecognized syndromic forms and of cases of ocular albinism in this prospective and comprehensive series of patients with albinism in a European setting is remarkable. Photoprotection was overall good but not optimal., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To clarify the relationships between marginal zone lymphomas (MZLs) and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (WM/LPLs), immunoglobulin heavy chain variable gene (IGHV) features were analyzed and the occurrence of MYD88 L265P mutations was identified in a series of 123 patients: 53 MZLs from the spleen (SMZLs), 11 from lymph nodes (NMZLs), 28 mucosa-associated lymphatic tissue (MALT) lymphomas and 31 WM/LPLs. SMZLs were characterized by overrepresentation of IGHV1-2 gene rearrangements with a canonical motif, without selection pressure and with long CDR3 segments. NMZLs had increased frequencies of IGHV3 genes. The IGHV gene was unmutated in most cases, often with long CDR3 segments. MALT lymphomas were usually associated with a mutated IGHV gene, but with the absence of selection pressure. WM/LPLs were associated with an IGHV3-23 overrepresentation and high IGHV mutation rate, with features of selection pressure and short CDR3 segments. MYD88 L265P mutations were almost restricted exclusively to WM/LPL patients. Taken all diagnoses together, all patients with MYD88 L265P mutations had an immunoglobulin M peak and almost all patients except one had bone marrow infiltration. These results demonstrate that the history of antigen exposure of the four entities studied was different and MYD88 L265P was specifically associated with WM/LPLs. WM/LPL may thus be functionally associated with constitutive nuclear factor-κB activation.

The liquid-ordered/disordered-phase domain co-existence in large unilamellar vesicle membranes consisting of phosphatidylcholine:sphingomyelin (2:1) with different amounts of cholesterol has been examined using a concentration-dependent self-quenching of a single reporter molecule, C12NBD-PC. A temperature-dependent decrease of fluorescence intensity was associated with the expected formation and increase of l(o)-phase membrane fraction in the vesicles. The result is consistent with exclusion of the fluorescent probe from the liquid-ordered phase which partitions preferentially into the liquid-disordered phase membrane domains. This leads to an increase of the local concentration of fluorophore in the liquid-disordered phase and a decrease of the quantum yield. This effect was used to obtain a quantitative estimation of the fraction of the vesicle membrane occupied by the liquid-ordered phase, Phi(o), as a function of temperature and cholesterol content between 0 and 45 mol%. The value of Phi(o) was related to the assumed partition coefficient k(p) of probe between liquid-ordered/disordered phases. For large unilamellar vesicles containing 20 and 4 mol% cholesterol and probe, respectively, with k(p) = 0 (probe completely excluded from liquid-ordered phase), Phi(o) = 0.16 and with k(p) = 0.2, Phi(o) = 0.2. The results are relevant to the action of detergent in the fractionation of detergent-resistant membrane from living cells.