Melanoma and intellectual disability: do prognostic factors at diagnosis differ from general population?

BACKGROUND: Few melanoma cases are reported in individuals with intellectual disability (ID), and prognostic factors at diagnosis are unknown in this population. This work was designed to investigate whether prognostic factors at diagnostic are different in patients with ID compared with a general population. METHODS: Melanoma cases retrieved from Hérault's Tumour Registry (HTR) from 1995 to 2015 were cross-referenced against a list of adult patients with ID, living in Hérault. Major prognostic factors were compared with those in non-ID melanoma patients included in HTR and in patients followed by Montpellier University Hospital and included in the Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome (RIC-Mel) database. RESULTS: Ten melanoma cases in individuals with ID were identified and compared with 3804 non-ID melanoma cases in HTR and 1024 non-ID melanoma cases included in RIC-Mel. Mean Breslow thickness at diagnosis was 4.6 mm in melanoma cases among those with ID versus 1.89 mm in HTR (P = 0.109) and 2.36 mm in RIC-Mel (P = 0.156). Stage at diagnosis was superior to stage IIB in 42.9% of ID cases versus 11.4% of non-ID cases in HTR (P < 0.05) and 8.5% in RIC-Mel (P < 0.05). CONCLUSIONS: Melanomas in patients with ID had less favourable prognostic factors at diagnosis, including higher Breslow thickness and more advanced stage, than melanomas in non-ID patients. These adverse prognostic factors indicate a later diagnosis in this population, leading to a poorer prognosis. This work underlines the need to improve melanoma screening among individuals with ID.

Severe and fatal forms of COVID-19 in children.

OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.

Management of 35 critically ill hyperammonemic neonates: Role of early administration of metabolite scavengers and continuous hemodialysis.

Neurological involvement is frequent in inherited metabolic disease of the intoxication type. Hyperammonemic coma related to these diseases may cause severe neurological sequelae. Early optimal treatment is mandatory combining metabolite scavengers (MS) and sometimes continuous veno-venous hemodialysis (CVVHD). We aimed to describe the therapeutic management of hyperammonemia in neonates upon diagnosis of their metabolic disease and to compare neonates managed with MS alone or with both MS and CVVHD. We conducted a retrospective study including all neonates admitted for initial hyperammonemia to the pediatric intensive care unit of a Reference Center of Inherited Metabolic Diseases, between 2001 and 2012. The study included 35 neonates. Before admission, MS were initiated for 11 neonates. At admission, the median ammonia levels were 391 µmol/L and were significantly lower in neonates who received MS before admission. At admission, ammonia levels were 644 µmol/L in dialyzed and 283 µmol/L in non-dialyzed neonates. The median time to reach a 50% decrease of the initial ammonia levels was significantly shorter in dialyzed neonates; however, the normalization of ammonia levels was similar between dialyzed and non-dialyzed neonates. Hemodynamic disorders were more frequent in dialyzed neonates. CONCLUSION: MS represent an effective treatment for hyperammonemia and should be available in all pediatric units to avoid the need for CVVHD. Although CVVHD enhances the kinetics of toxic metabolite decrease, it is associated with adverse hemodynamic effects.

Somatic assessment of one hundred inpatients in a psychiatric crisis unit: A retrospective observational study.

OBJECTIVES: Compared to the general population, psychiatric patients are more exposed to physical illness but have reduced access to care. METHODS: We conducted a descriptive study in Montpellier between November 2011, 2nd and December 2012, 21st. Every Wednesday and Friday, the last two inpatients admitted in the psychiatric post-emergency unit of the University Hospital of Montpellier were assessed by a general practitioner and included in the study. This unit takes care of suicidal patients suffering from mood and/or personality disorders. The general practitioner assessed lifetime somatic history, current somatic comorbidities and medical follow-up for non-psychiatric issues. RESULTS: One hundred patients were included. The sample consisted of 81% women with a mean age of 43 years (18-79 years). The majority of patients had a lifetime history of somatic disease (96%) and was followed by a general practitioner (99%). Six patients had no met general practitioner for at least one year. Dyslipidemia was reported in 32 patients, among those only one patient was on lipid-lowering drug (96.88%). Among patients with impaired dental condition, 29 (55.77%) had not met a dentist for at least one year. Among those with impaired near visual acuity and/or impaired distance visual acuity, 19 (65.52%) had not met an ophthalmologist for at least one year. CONCLUSION: Although detected, somatic comorbidities seem outsourced in psychiatric patients. Greater awareness among different health professionals about the medical care of such patients could improve healthcare management and life expectancy.

Postdiarrheal hemolytic and uremic syndrome with severe multiorgan involvement and associated early risk factors.

AIM: Identifying early clinical and biological factors associated with severe forms of postdiarrheal hemolytic uremic syndrome (D+HUS) that may help practitioners determine appropriate treatment. METHODS: This retrospective study was conducted in 49 children with D+HUS between 2001 and 2011. Severe forms were defined as occurrence of one of the following conditions: death, major neurological involvement, cardiovascular involvement, and/or the presence of sequelae (neurological, cardiovascular, pancreatic, or renal). RESULTS: During the acute phase, 35 children exhibited at least one type of extrarenal involvement including 13 severe forms with a median delayed occurrence after admission of 4.5 days (range: 1-8) for comatose children and 5 days (range: 2-6) for cardiovascular involvement; 32 children required dialysis and three died. In multivariate analysis, (i) major neurological involvement (n=13), (ii) dialysis (n=32), and (iii) sequelae (n=12) were associated with (i) fever during the prodromal phase requiring dialysis at admission, (ii) C-reactive protein level (CRP) >22mg/L at admission, and (iii) major neurological involvement and a white blood cell count (WBC)>20×103/mm3 during the acute stage, respectively. CONCLUSIONS: D+HUS is a multiorgan disease with a delayed occurrence of life-threatening extrarenal organ involvement. Severe forms appear to be associated with early biological and clinical inflammatory parameters.

Prenatal factors associated with neonatal survival of infants with congenital chylothorax.

OBJECTIVES: Congenital chylothorax is a rare disease and prognostic factors are key element in properly informing parents. This study aimed at determining the prenatal factors associated with neonatal survival in a cohort of liveborn infants with congenital chylothorax. STUDY DESIGN: Observational monocentric cohort study including all liveborn neonates consecutively admitted for congenital chylothorax. RESULTS: Neonatal mortality was 32% (16/50). Prematurity (or birth weight), persistence of hydrops at birth and the absence of thoracoamniotic shunt procedure were significantly associated with mortality, whereas prenatal diagnosis of pleural effusion, side of pleural effusion, hydrops fetalis and amniodrainage were not. In case of prenatal diagnosis of hydrops fetalis, the reversal in utero of hydrops fetalis was significantly associated with survival (P=0.001). In case of thoracoamniotic shunting, the interval between thoracoamniotic shunting intervention and delivery was significantly longer for patients who survived (P=0.03). CONCLUSIONS: Thoracoamniotic shunting and reversal of hydrops significantly improves survival, whereas prematurity worsened outcome of liveborn infants with congenital chylothorax. Our data also suggest that the interval between thoracoamniotic shunting and birth appears to be crucial; the longer the interval, the more likely is the reversal of antenatal hydrops and neonatal survival.

[Acute hemorrhagic edema of infancy associated with Coxsackie virus infection]. / Œdème aigu hémorragique du nourrisson associé à une infection à Coxsackie virus.

Acute hemorrhagic edema of infancy is a rare but benign vasculitis occurring in infants aged from 4 to 24 months. Skin lesions can take various forms, including extensive hemorrhagic purpura, and can therefore be mistaken for purpura fulminans if associated with fever, which leads to initiating broad-spectrum antibiotic treatment. In the present case, we describe a 7-month-old boy with acute hemorrhagic edema of infancy and rapidly extensive purpura lesions that led to intravenous cefotaxime and amikacin treatment. Diagnosis was made on the next day by a dermatologist, based on the typical aspect of skin lesions, hemodynamic stability, and negative bacteriological samples. Coxsackie virus B5, a pathogenic enterovirus, was found by specific PCR in cerebrospinal fluid. The outcome was spontaneously favorable after discontinuation of antibiotics on day 2. We discuss the imputability of the enterovirus in triggering this case of acute hemorrhagic edema of infancy.

Minimal modulation of the host immune response to SIS matrix implants by mesenchymal stem cells from the amniotic fluid.

PURPOSE: Surgical restoration of soft tissue defects often requires implantable devices. The clinical outcome of the surgery is determined by the properties inherent to the used matrix. Mesenchymal stem cells (MSC) modulate the immune processes after in vivo transplantation and their addition to matrices is associated with constructive remodeling. Herein we evaluate the potential of MSC derived from the amniotic fluid (AF-MSC), an interesting MSC source for cell therapeutic applications in the perinatal period, for immune modulation when added to a biomaterial. METHODS: We implant cell free small intestinal submucosa (SIS) or SIS seeded with AF-MSC at a density of 1 × 105/cm2 subcutaneously at the abdominal wall in immune competent rats. The host immune response is evaluated at 3, 7 and 14 days postoperatively. RESULTS: The matrix-specific or cellular characteristics are not altered after 24 h of in vitro co-culture of SIS with AF-MSC. The host immune response was not different between animals implanted with cell free or AF-MSC-seeded SIS in terms of cellular infiltration, vascularity, macrophage polarization or scaffold replacement. Profiling the mRNA expression level of inflammatory cytokines at the matrix interface shows a significant reduction in the expression of the pro-inflammatory marker Tnf-α and a trend towards lower iNos expression upon AF-MSC-seeding of the SIS matrix. Anti-inflammatory marker expression does not alter upon cell seeding of matrix implants. CONCLUSION: We conclude that SIS is a suitable substrate for in vitro culture of AF-MSC and fibroblasts. AF-MSC addition to SIS does not significantly modulate the host immune response after subcutaneous implantation in rats.

Cellular origin of intrinsic optical signals in the rabbit retina.

Optical imaging of retinal intrinsic signals is a relatively new method that provides spatiotemporal patterns of retinal activity through activity-dependent changes in light reflectance of the retina. The exact physiological mechanisms at the origin of retinal intrinsic signals are poorly understood and there are significant inter-species differences in their characteristics and cellular origins. In this study, we re-examined this issue through pharmacological dissection of retinal intrinsic signals in the rabbit with simultaneous ERG recordings. Retinal intrinsic signals faithfully reflected retinal activity as their amplitude was strongly associated with stimulation intensity (r2=0.85). Further, a strong linear relation was found using linear regression (r2=0.98) between retinal intrinsic signal amplitude and the ERG b wave, which suggests common cellular origins. Intravitreal injections of pharmacological agents were performed to isolate the activity of the retina's major cell types. Retinal intrinsic signals were abolished when the photoreceptors' activity was isolated with aspartate, indicative that they are not at the origin of this signal. A small but significant decrease in intrinsic response (20%) was observed when ganglion and amacrine cells' activity was inhibited by TTX injections. The remaining intrinsic responses were abolished in a dose-dependent manner through the inhibition of ON-bipolar cells by APB. Our results indicate that, in rabbits, retinal intrinsic signals reflect stimulation intensity and originate from the inner retina with a major contribution of bipolar cells and a minor one from ganglion or amacrine cells.

[Accidental amphetamine poisoning in an 11-month-old boy]. / Intoxication involontaire aux amphétamines chez un nourrisson de 11 mois.

INTRODUCTION: In France, the use of illicit drugs is increasing and therefore accidental poisoning may occur in infants and children. We report on a case of ecstasy poisoning in an infant who presented with atypical neurological symptoms. CASE REPORT: An 11-month-old infant suddenly developed agitation with eye rolling and unreactive bilateral mydriasis. All neurologic causes were excluded. The search for toxicants revealed an intoxication with an amphetamine and MDMA. Progression was favorable in 24h. CONCLUSION: Although rare, pediatric intoxications by ecstasy have become more common in recent years, due to its consumption within households, exposing young children and infants to accidental ingestion of a tablet of ecstasy.

Brain hemodynamic response to somatosensory stimulation in Neuroligin-1 knockout mice.

Neuroligin 1 (NLGN1) is a postsynaptic adhesion molecule that determines N-methyl-d-aspartate receptor (NMDAR) function and cellular localization. Our recent work showed that Nlgn1 knockout (KO) mice cannot sustain neuronal activity occurring during wakefulness for a prolonged period of time. Since NMDAR-dependent neuronal activity drives an important vascular response, we used multispectral optical imaging to determine if the hemodynamic response to neuronal stimulation is modified in Nlgn1 KO mice. We observed that Nlgn1 KO mice show a 10% lower response rate to forepaw electrical stimulation compared to wild-type (WT) and heterozygote (HET) littermates on both the contra- and ipsilateral sides of the somatosensory cortex. Moreover, Nlgn1 mutant mice showed an earlier oxyhemoglobin peak response that tended to return to baseline faster than in WT mice. Analysis of the time course of the hemodynamic response also showed that HET mice express a faster dynamics of cerebrovascular response in comparison to WT. Taken together, these data are indicative of an altered immediate response of the brain to peripheral stimulation in Nlgn1 KO mice, and suggest a role for NLGN1 in the regulation of cerebrovascular responses.

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink.

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.

[French law related to patient's rights and end of life: pediatric intensive care unit's health professionals' opinions]. / Opinions des soignants des réanimations pédiatriques françaises sur l'application de la loi Léonetti.

INTRODUCTION AND OBJECTIVES: To identify the knowledge of caregivers of pediatric intensive care units (PICUs) on the French law related to patients' rights and end of life, their views on withholding/withdrawing life-sustaining treatment (WWLST) decisions, and their feelings about how these decisions were made and implemented. MATERIALS AND METHODS: A multicenter survey in 24 French PICUs during the fourth trimester 2010. RESULTS: One thousand three hundred and thirty-nine professional healthcare workers (1005 paramedics and 334 physicians) responded. Over 85% of caregivers had good knowledge of the WWLST decision-making processes required by law. More than 80% of caregivers accepted mechanical ventilation, hemodiafiltration, or hemodynamic support withdrawal or withholding. Nevertheless, the withdrawal of artificial nutrition and hydration generated reluctance or opposition for the majority of respondents. While paramedics' participation in the decision-making process was deemed necessary by all caregivers, paramedics found more often than physicians that they were insufficiently involved. The quality of end-of-life care was judged very positively by caregivers. The answers on how WWLST was applied suggest very different interpretations of the law. Some caregivers respect the principles of palliative care as stated in the public health code and 40% of doctors and 64% of caregivers consider it "acceptable" to hasten death if resulting from a collaborative decision-making process. CONCLUSION: This study is the first to show that caregivers of French PICUs have good knowledge of the French law concerning the end of life. Yet, there is still confusion about the limits of practice during the end-of-life period.

Mucormycosis as a rare cause of severe gastrointestinal bleeding after multivisceral transplantation.

Mucormycosis, an emerging fungal infection in solid organ transplant patients, is mostly located in rhino-orbito-cerebral, pulmonary, and cutaneous areas, or disseminated with poor prognosis. A 4-year-old girl with chronic intestinal pseudo-obstruction syndrome underwent a modified multivisceral transplantation, including half of the stomach, the duodeno-pancreas, the small bowel, and the right colon. On postoperative day 5, a digestive perforation was suspected. Surgical exploration found a small necrotic area on the native stomach, which was externally drained. The next day, massive gastric bleeding occurred. During the emergency laparotomy, 2 hemorrhagic ulcers were found and resected from the transplanted stomach. Pathology and fungal culture showed mucormycosis caused by Lichtheimia (formerly Absidia) ramosa in both the transplanted and native stomach. High-dose intravenous liposomal amphotericin B was immediately started. No other site of fungal infection was found. The child recovered, and 3 years after transplantation, is alive and well, off parenteral nutrition. The originality of this case is the very early presentation after transplantation, the unusual site, and the complete recovery after rapid medico-surgical management. The origin of the fungus and treatment are discussed.

Clinical stress assessment using a visual analogue scale.

BACKGROUND: Clinicians increasingly require short, efficient methods for assessing distress, both in applied research and clinical settings. Most of the available questionnaires are unsuitable for busy clinical settings. The visual analogue scale (VAS) is widely but empirically used to assess perceived stress. AIMS: To provide evidence on two of the psychometric properties of the VAS: its discriminative sensitivity (capacity to highlight a difference between groups) and its interconcept validity (the relationship between VAS stress assessment and the assessment of different, but similar concepts). METHODS: Employees attending occupational health centres were randomly selected and completed the VAS and also either the Perceived Stress Scale (PSS) or the Hospital Anxiety and Depression Scale (HADS). Analyses of variance were performed to study group effects (age, sex, marital status, parental status, occupational status) on stress scores (PSS and VAS). RESULTS: In total, 763 employees participated of whom 501 completed the PSS and 262 the HADS. P-values obtained for the effects of sex, age and occupational status were lower with the VAS than with the PSS. Correlations between the VAS and the anxiety subscale, depression subscale and total score of the HADS were 0.66, 0.45 and 0.65, respectively. Other tools used to assess aspects of psychological distress are known to have similar correlations. CONCLUSIONS: Our findings provide evidence that the VAS is at least as discriminating as a questionnaire when it comes to highlighting differences in stress levels between two groups, and the observed correlations with related constructs support its construct validity.

[Local salicylate transcutaneous absorption: an unrecognized risk of severe intoxication: a case report]. / Application cutanée localisée d'acide salicylique : un risque méconnu d'intoxication : à propos d'un cas.

INTRODUCTION: Although rare, salicylate intoxication through the skin should not be ignored as it can be severely life-threatening. We describe an original case of accidental poisoning with salicylates topically applied to the scalp of a 6-week-old infant. CLINICAL REPORT: A 6-week-old infant, with no prior history, was admitted to the pediatric intensive care unit for treatment of severe disorders of consciousness associated with significant tachypnea. Laboratory results revealed metabolic acidosis with elevated anion gap, ketonuria, and normal glycemia. Initial assessment ruled out the hypothesis of accidental ingestion of salicylates. However, the presence of salicylic acid derivatives in organic acid chromatography, confirmed by plasma salicylate levels at 580 mg/L, ultimately re-established the diagnosis. Further inquiry retrospectively highlighted the prolonged topical application in occlusion (3 days) of an extemporaneous preparation containing 23% salicylic acid on the scalp. The course after urine alkalinization was rapidly favorable without sequelae. COMMENT AND CONCLUSIONS: Salicylate intoxication is potentially lethal, particularly in infants under 12 months of age. The vast majority of these intoxications result from accidental ingestion. The present observation underscores the original and undescribed risk of intoxication due to a localized application to the scalp. In the presence of warning symptoms, salicylate poisoning should be investigated, including topical application of salicylic acid, even if localized. Careful attention should be paid to following the indications of use of this product in terms of concentration, characteristics of the infant, and exposed skin. The use of extended topical application of salicylic acid in concentrations greater than 3% should be avoided.

Neurovascular deconvolution of optical signals as a proxy for the true neuronal inputs.

UNLABELLED: Since the Kalman filter and Monte Carlo techniques, much theoretical work has been put into the development of signal deconvolution tools. Among recent developments taking place in neuroscience are Dynamic Expectation Maximization, Generalized Filtering and the Cubature Kalman Filter. While there are exciting prospects to use these tools for Dynamic Causal Modeling and other analyses of networks, there has been comparatively little work to validate the algorithms on controlled experimental data. In this work, the latest evolution of these tools, the square-root cubature Kalman smoother (SCKS), is tested for its effectiveness on multimodal neurovascular data. Multispectral intrinsic optical imaging and electrophysiological measurements of Wistar rats are used in combination with somatosensory stimulation. The Buxton-Friston (B-F) balloon model is then deconvolved with the SCKS algorithm to obtain the estimated neuronal inputs u(t) from the hemodynamic measurements (flow, oxy- and deoxygenated hemoglobin). RESULTS: The estimated neuronal inputs are compared to the stimulation protocol and a sensitivity and specificity analysis is carried out. SCKS succeeds in recovering most of the stimulations. Next, the estimated inputs are compared to actual measures of neuronal activity: local field potentials (LFPs) and multiunit activity (MUA). Good sensitivity of the technique is obtained with both LFPs and MUA over the whole recordings, with the area of the ROC curves favoring LFPs. A weak correlation between SCKS estimated inputs and LFPs is found outside stimulation periods, significant at one standard deviation. Finally, the accuracy of state reconstructions is studied and SCKS reconstructed states are highly concordant with measured states.