Graves' orbitopathy post-SARS-CoV-2 vaccines: report on six patients.

CONTEXT: Autoimmune and inflammatory thyroid diseases (Graves' disease, subacute thyroiditis, chronic autoimmune thyroiditis) have been reported following SARS-CoV-2 vaccines but Graves' orbitopathy (GO) post-COVID-19 vaccination is uncommon. METHODS: We describe six new patients seen in Endocrinology Departments with Outpatient Clinics for GO following SARS-CoV-2 vaccines in France. RESULTS: After COVID-19 vaccination, GO was observed in six patients (three men, three women, mean age 53 ± 6 years) with a personal past history of Graves' disease (5/6) or orbitopathy (4/6). New-onset (n = 2) or recurrence (n = 4) of GO was observed following mRNA vaccines after the first (3/6) or second (3/6) dose, with the mean time from vaccination to GO at 23.8 ± 10.4 days. In one patient, thyrotoxicosis was confirmed by increased free T4 and low TSH concentrations while others had normal TSH levels, during chronic levothyroxine treatment in three patients. Four patients had significant anti-TSH receptor antibodies levels. According to the severity and activity of GO, the patients were treated using selenium (n = 2), intravenous glucocorticoids (n = 2), teprotumumab (n = 1), tocilizumab (n = 2) and orbital decompression (n = 1) with a significant improvement in GO signs and symptoms observed by most patients. CONCLUSION: In this study, we report the main data from six new patients with GO following SARS-CoV-2 vaccines. Clinicians need to be aware of the risk of new-onset or recurrent GO in predisposed patients with autoimmune thyroid diseases after COVID-19 vaccination. This study should not raise any concerns regarding SARS-CoV-2 vaccination since the risk of COVID-19 undoubtedly outweighs the incidence of uncommon GO after SARS-CoV-2 vaccination.

Renal and overall outcomes of double-positive (ANCA and anti-GBM antibodies) patients compared to ANCA-associated vasculitis patients with severe renal involvement: A multicenter retrospective study with systematic renal pathology analysis.

OBJECTIVE: Double-positive patients (DPPs), combining serum and/or histological findings for glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic antibodies (ANCAs), are rare and poorly described. This study aimed to compare characteristics between DPPs and ANCA-associated vasculitis (AAV) patients with severe renal involvement. METHOD: This retrospective multicentre study compared 33 DPPs and 45 AAV patients with severe renal involvement (serum creatinine > 300 µmol/L), all with biopsy-proven nephropathy. RESULTS: All DPPs (including 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histological GBM involvement. Compared to AAV patients, they had higher serum creatinine (719 vs 501 µmol/L; p = 0.006) and a higher proportion of patients requiring initial renal replacement therapy (82% vs 36%; p < 0.001). Berden classification differed significantly (p = 0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPPs. One-year renal survival was significantly lower in DPPs than in AAV patients (27% vs 64%; p < 0.0002). With comparable proportions of ANCA subtypes (two-thirds with anti-myeloperoxidase autoantibodies), numbers of extrarenal manifestations (mostly pulmonary in two-thirds), remission-inducing immunosuppressants, and median follow-ups (3 years) between groups, relapse rates were similar: 9.1% of DPPs and 10% of AAV patients. CONCLUSION: Although DPPs have features of both kinds of vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAV patients with severe renal failure. Simultaneous testing of both antibodies and systematically performed renal biopsy should be recommended in all rapidly progressing glomerulonephritis patients to recognize this difficult-to-treat, rare disease.

Near-field airborne particle concentrations in young children undergoing high-flow nasal cannula therapy: a pilot study.

BACKGROUND: High-flow nasal cannula therapy (HFNC) may increase aerosol generation, putting healthcare workers at risk, including from SARS-CoV-2. AIM: To examine whether use of HFNC increases near-field aerosols and whether there is an association with flow rate. METHODS: Subjects aged four weeks to 24 months were recruited. Each child received HFNC therapy at different flow rates. Three stations with particle counters were deployed to measure particle concentrations and dispersion in the room: station 1 within 0.5 m, station 2 at 2 m, and station 3 on the other side of the room. Carbon dioxide (CO2) and relative humidity were measured. Far-field measurements were used to adjust the near-field measurements. FINDINGS: Ten children were enrolled, aged from 6 to 24 months (median: 9). Elevated CO2 indicated that the near-field measurements were in the breathing plane. Near-field breathing plane concentrations of aerosols with diameter 0.3-10 µm were elevated by the presence of the patient with no HFNC flow, relative to the room far-field, by 0.45 particles/cm3. Whereas variability between subjects in their emission and dispersion of particles was observed, no association was found between HFNC use, at any flow rate, and near-field particle counts. CONCLUSION: This method of particle sampling is feasible in hospital settings; correcting the near-patient aerosol and CO2 levels for the room far-field may provide proxies of exposure risk to pathogens generated. In this pilot, near-patient levels of particles with a diameter between 0.3 and 10 µm and CO2 were not affected by the use of HFNC.

[Social cognition in schizophrenia and autism spectrum disorder: Points of convergence and functional differences]. / Cognition sociale dans la schizophrénie et les troubles du spectre de l'autisme : points de convergences et différences fonctionnelles.

INTRODUCTION: Schizophrenia and autistic spectrum disorder (ASD) are two neurodevelopmental disorders that have different symptom presentations, ages of onset and developmental courses. Both schizophrenia and ASD are characterized by marked deficit in communication, social interactions, affects and emotions. Social cognitive impairments in ASD and schizophrenia were demonstrated separately in both disorders. It was reported that these impairments have direct relation with social deficits of both disorders. The apparent similarity between social cognition impairments in ASD and schizophrenia highlights questions about the existence of common or different neurocognitive mechanisms related to social dysfunctions. In order to examine these questions, the present article provides a comprehensive review of all published studies which directly compare individuals with ASD and schizophrenia on the same cognitive tasks of social cognition. METHODS: The article search was made on Pubmed, PsycInfo and ScienceDirect, with the items: "autism", "Asperger syndrome", "schizophrenia", "social cognition", "theory of mind", "emotional processing", "social perception", "attributions style". All published studies which compared individuals with ASD and schizophrenia, (diagnosed according to DSM-IV (APA, 1994) criteria and IQ≥70), included control group were considered. The cognitive tasks were categorized according to four domains of social cognition defined by SCOPE (Pinkham et al., 2013): theory of mind (ToM), emotional processing (EP), social perception (SP) and attributional style/bias. The results were analyzed in terms of performances, cognitive profile and patterns of neural activations. Twenty-one published studies and two meta-analytic reviews were analyzed. RESULTS: Cognitive performance analysis confirms the convergence of abnormalities of people with autism and people with schizophrenia on 1st and 2nd order theory of mind, emotion processing and social perception. Quantitative results show reduced performance in ASD compared to SZ and Ct groups. Differences were observed between ASD and SZ regarding social situation comprehension, visual orientation and visuospatial exploration strategies, and attributional style highlighting different strategies on intentional process. Brain imaging studies show that people with autism present a reduced cerebral activity in several key regions of theory of mind (cingulate regions, superior temporal sulcus, paracentral lobule), and emotional treatment (primary and secondary somatosensory regions), while people with SZ exhibit an inappropriate increased activity in these regions. CONCLUSION: The present revue of the studies which directly compare individuals with ASD and schizophrenia on different domains of social cognition indicates that both disorders exhibit differences and similarities with regard to behavioral performances. Results in neuroimaging indicate different neurocognitive mechanisms underlie apparently similar social-cognitive impairments. Further studies are needed to better explore and describe divergent neurocognitive mechanisms in ASD and schizophrenia in order to provide treatment and remediation methods that take into account the specificities of neurocognitive processes in the two disorders.

Early barriers to neonatal porcine islet engraftment in a dual transplant model.

Porcine islet xenografts have the potential to provide an inexhaustible source of islets for ß cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared with rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling])-positive cells) of NPIs compared with AIs. Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (wild-type) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (α1,3-galactosyltransferase knockout) compared with AIs. These findings demonstrate an augmented macrophage and antibody response toward xenografts compared with allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.

The predictor of mortality outcome in adult patients with Ebola virus disease during the 2014-2015 outbreak in Guinea.

The purpose of this study was to examine the association of any demographic and clinical factors with mortality outcome among adult patients with Ebola virus disease (EVD) in Guinea. This retrospective observational study analyzed medical records of laboratory confirmed EVD adult patients during the 2014-2015 EVD outbreak in Guinea. The associations between any demographic or clinical variables and mortality outcome of EVD were assessed using univariate and multivariate logistic regression analyses. Of 2,310 EVD adult patients included for analysis, the overall case fatality rate was 68.1%. Univariate analyses identified factors possibly associated with mortality outcome, including patient age (p < 0.001), history of visiting or close contact with a suspected or confirmed EVD patient (p = 0.035), and seven clinical symptoms on admission, i.e., fever (p = 0.003), hiccups (p < 0.001), vomiting (p = 0.003), diarrhea (p < 0.001), cough (p = 0.001), sore throat (p = 0.016), and unexplained bleeding (p = 0.021). The multivariate analysis showed that patient age was independently associated with mortality outcome of EVD (OR = 1.06; 95%CI = 1.03-1.09; p < 0.001), while none the of clinical symptoms on admission were significantly associated with the mortality outcome. Our analysis indicates that older age was the only independent factor associated with death among EVD adult patients in Guinea. This suggests that older EVD patients should receive intensive medical care and be carefully monitored.

Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5-312) weeks following the transplant procedure. Patients had delayed graft function (n=2), acute-on-chronic (n=5) or acute (n=1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n=7), remained stable (n=1) or worsened (n=1). At last follow-up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.

[Iron deficiency in children and teenagers: a health problem that is still present]. / La carence en fer chez l'enfant et l'adolescent : un problème toujours d'actualité

Iron deficiency remains a problem in developing countries as well as in industrial nations. The prevalence of iron deficiency in children under 5 years of age is identical in Europe and the USA, and is in the order of 7 to 9% on average with an anaemia prevalence of 2.3%. The major cause is dietary deficiency, particularly in premature babies, infants, teenagers, and children in unstable situations. It is important to prevent the development of anaemia, especially in infants, due to its morbid consequences particularly with respect to development. Screening and simple preventative measures (iron supplements and dietary advice) need to be systematically set up, particularly in at-risk populations, and are detailed in the present article.

[Childhood cancer incidence in French Brittany, 1991-2005]. / Incidence des cancers de l'enfant en Bretagne entre 1991 et 2005.

BACKGROUND: The aim of this study was to describe childhood cancer incidence in French Brittany from 1991 to 2005, as well as its temporal and geographical variations. METHODS: Childhood cancer incidence was analyzed from the data from the Brittany child tumor registry. Crude rates, world age standardized rates and cumulative rates were estimated for all cancers and for each diagnosis group. Standardized rates were also estimated for each of the four Brittany districts. Poisson regressions were performed to estimate trends in annual rates and to compare incidence rates between 2000-2005 and 1991-1999 periods, and between districts. RESULTS: Between 1991 and 2005, 1176 incident cancer cases were recorded in children younger than 15. Age standardized incidence was 169.5 cases per million of children per year. The most frequent cancers were leukemia (30%), central nervous system tumors (24%), lymphomas (12%) and neuroblastomas (8%). For the period 1991-2005 in Brittany, the risk of cancer diagnosis among children aged less than 15 years was 1/459. No significant increase trend was observed over the 1991-2005 period. There was however a significant or close to significant increase in incidence for lymphomas (RR: 1.38 [95%CI: 1.00-1.93]) and central nervous system tumors (RR: 1.24 [95%CI: 0.99-1.56]) between the 1991-1999 and 2000-2005 periods. A significant decrease trend was observed for renal tumors over the 1991-2005 period (Estimated Annual Percent Change=-7.6%, P=0.02). There was no significant difference of incidence between the four districts of the region. CONCLUSION: For the period studied, childhood cancer incidence in French Brittany was lightly higher than for the whole country. Although increases in lymphomas and central nervous system tumors coincided with increasing use of a standardised data collection system for medical information, the data collected provided no evidence in favor of more complete data collection following implementation of the system.

Diagnosis of fetal urinary tract malformations: prenatal management and postnatal outcome.

OBJECTIVE: To evaluate prenatal management and to define the criteria of gravity for accurate assessment of the renal and overall prognosis of fetuses presenting malformations of the urinary tract. METHODS: We carried out a retrospective study of 127 cases of urinary tract malformation. We carried out descriptive statistical and univariate analyses as a function of severity criteria and the outcome of pregnancy. RESULTS: One-third of fetuses presented associated extrarenal malformations and 10% of the karyotypes were abnormal. There were more abortions in case of decrease in amniotic fluid volume (p < 0.001), extent of renal damage (p < 0.05), presence of associated extrarenal malformations (p < 0.05), early diagnosis of the malformation (p < 0.001) and presence of chromosomal syndrome (p = 0.01). In our study, there was an excellent correlation between prenatal data and pathological findings for the fetus following abortions for medical reasons or obtained during the surveillance of live-born children. Fetal biochemistry made very little contribution. CONCLUSION: In cases of urinary tract malformation, this work confirms the need for regular and frequent ultrasound scans, checking for the echographic factors indicative of gravity and for adapted karyotyping. It also demonstrates that pluridisciplinary management is necessary for the prenatal evaluation of renal and overall fetal prognosis.

Outbreak of Serratia marcescens in a neonatal intensive care unit: contaminated unmedicated liquid soap and risk factors.

This study describes an outbreak of Serratia marcescens and its investigation and control in a neonatal intensive care unit (NICU). During a three-month period, five infants were colonised or infected by a single strain of S. marcescens. A case-control study, culture surveys and pulse-field gel electrophoresis analysis implicated a bottle soap dispenser as a reservoir of S. marcescens (P=0.032). Infants with S. marcescens colonisation or infection were also more likely to have been exposed to a central or percutaneous venous catheter (P=0.05) and had had longer exposure to endotracheal intubation (P=0.05). Soap dispensers are used in many hospitals and may be an unrecognised source of nosocomial infections. This potential source of infection could be reduced by using 'airless' dispensers which have no air intake for the distribution of soap. Prompt intervention and strict adherence to alcoholic hand disinfection were the key factors that led to the successful control of this outbreak.

Antipyretic efficacy and safety of a single intravenous administration of 15 mg/kg paracetamol versus 30 mg/kg propacetamol in children with acute fever due to infection.

OBJECTIVES: An intravenous formulation of paracetamol and an intravenous formulation of propacetamol (prodrug of paracetamol) were compared in children with acute fever due to infection in order to determine the antipyretic efficacy and safety during the 6-hour period after administration. METHODS: A total of 67 patients aged 1 month to 12 years and with a rectal body temperature between 38.5 degrees C and 41 degrees C, were randomized to receive either intravenous paracetamol 15 mg/kg (n = 35) or propacetamol 30 mg/kg (n = 32) under double-blind conditions. RESULTS: The non-inferiority of intravenous paracetamol compared to propacetamol was demonstrated (non-inferiority margin = 0.5 degrees C) by the median body temperature reduction of 1.9 degrees C in the intravenous paracetamol group and the reduction of 2.05 degrees C in the propacetamol group. The difference in the incidence of local adverse events was statistically significant (p = 0.0134) with more local adverse events in the propacetamol group (9, 28.1%) than in the intravenous paracetamol group (2, 5.7%). CONCLUSION: This double-blind, randomized, clinical trial demonstrates the non-inferiority of a single administration of 15 mg/kg intravenous paracetamol in comparison to 30 mg/kg propacetamol in terms of body temperature reduction in children aged 1 month to 12 years with acute fever due to infection. It confirms the better local safety of intravenous paracetamol in comparison to propacetamol.

[Severe asthma due to an esophageal foreign body in a child]. / Un asthme rebelle en rapport avec un corps étranger oesophagien méconnu.

A 4-year-old boy had infantile bronchial asthma resistant to treatment. He was referred for a febrile respiratory distress which led to the diagnosis of periesophagus mediastinis mass with erosion of both contiguous vertebral discs. The oesophagogram showed a foreign body in an esophageal diverticulum. After its extraction, all pulmonary symptoms disappeared.

[Endoscopic therapy for pancreatitis in children]. / Endoscopie interventionnelle dans les pancréatites de l'enfant.

Authors report on 3 cases of children treated by therapeutic endoscopic retrograde cholangiopancreatography for pancreatitis (ERCP). The first child presented with familial pancreatitis: he was treated by sphincterotomy and lithiasis extraction. The second child presented with pancreatitis secondary to pancreas divisum: she was treated by sphincterotomy and stunt of small caroncula. The third child presented with severe pancreatitis with pseudocyst: after drainage she was treated by sphincterotomy, Wirsung dilatation and lithiasis extraction. ERCP is a beneficial treatment and may be alternative to surgery in complicated pancreatitis.

[Hemorrhagic colitis in exclusively breast-fed infants]. / Colite hémorragique chez les nourrissons en allaitement maternel exclusif.

INTRODUCTION: Authors report clinical, biological and endoscopic data of six children aged less 3 months with bloody stools while they were exclusively breast-fed. RESULTS: Two girls and four boys aged 1 to 2 months presented with isolated but recurrent rectal bleeding. All were explored by fiberoptic rectosigmoidoscopy between 1 and 3,2 months. Macroscopic aspects were congestion (6 cases), petechial and ecchymotic (4 cases), with normal mucosal areas (5 cases). Histopathology showed eosinophilic infiltrates in all 5 children with rectal biopsy. Evolution was satisfactory after cow's milk protein exclusion in maternal diet for five children and after weaning in 1. All children were weaned with protein hydrolysate. Cow's milk protein were later introduced without adverse reactions at 6 to 23 months. CONCLUSION: Food allergy can be considered in proctocolitis including exclusive breast-fed children. Evolution after maternal diet is, as usual, simple.

[Factors associated with the choice of breast or bottle-feeding for hospitalized newborns]. / Facteurs associés au choix du mode d'alimentation pour un nouveau-né hospitalisé.

UNLABELLED: This study was carried out in Rennes's maternity hospitals (France), to determine the breastfeeding rate for newborns hospitalized after birth, as well as the factors associated with the choice to breastfeed or not in these conditions. METHODS: Three hundred and twenty mothers delivered in Rennes Teaching Hospital, whose neonates were transferred in neonatal care unit, were questioned about their choice for neonate feeding. RESULTS: Three hundred and eight of the 320 mothers concerned by the study answered our interview. Fifty one percent of them chose to breast feed, which is near the breastfeeding rate of the general population of Rennes' maternity hospitals (52%). A high sociocultural level, a mother previously breastfed herself, and a previous breast feeding (RR = 5.2; P < 10(-8)) were associated with the choice of breastfeeding. Factors concerning the information of the mothers were also associated with the choice of breastfeeding information during the preparation to birth sessions (RR = 1.7; P < 10(-5)), individual information on the breastfeeding of an ill newborn (RR = 1.5; P < 0.01), and the simple advice to breastfeed given by a health care professional (RR = 2; P < 10(-8)). Of the four qualities named, the more breast-milk qualities a mother knew, the higher breastfeeding rate was (10% for none, 27% for one, 54% for two, and 76% for three or four). Concerning the postnatal factors, gestational age below 31 weeks multiplied breast feeding by 1.5 (P < 0.05), and an early contact mother-child (first day) by 1.3 (P < 0.05). CONCLUSION: This study pointed out the populations at risk of no breastfeeding. Informations on the properties of breastfeeding given to mothers by health care professionals may influence them in their choice of breast feeding or not their ill newborn.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

SLE in a United States-Mexico border community.

This report describes the results of a clinic-based study conducted to verify a community-reported excess prevalence of systemic lupus erythematosus (SLE) and a possible connection between ethnicity and environmental factors in the reporting of SLE in the United States-Mexico border town of Nogales, Arizona. A community group in Nogales reported 37 cases of SLE in its community, suggesting a prevalence rate of 200 per 100,000. This report describes 19 definite and 7 probable cases of SLE using the 1982 American College of Rheumatology criteria. All definite and probable cases were self-identified, Mexican-American females. This yields a prevalence rate of 94 per 100,000, among the highest reported to date. The majority of cases resided within 3 miles of the United States-Mexico border and within 1 mile of the polluted Nogales Wash or ground wells with documented toxins. It remains to be determined whether this confirms that SLE is more common in Mexican-Americans or whether environmental factors, especially pollutants, are predominantly responsible. In addition to the need to be aware about the apparent increased risk of SLE in many Latin-Americans, clinicians should ask about possible environmental factors.