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.

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.

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.

Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: a model of healthy aging.

The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

Biophysical model estimation of neurovascular parameters in a rat model of healthy aging.

Neuronal, vascular and metabolic factors result in a deterioration of the cerebral hemodynamic response with age. The interpretation of neuroimaging studies in the context of aging is rendered difficult due to the challenge in untangling the composite effect of these modifications. In this work we integrate multimodal optical imaging in biophysical models to investigate vascular and metabolic changes occurring in aging. Multispectral intrinsic optical imaging of an animal model of healthy aging, the LOU/c rat, is used in combination with somatosensory stimulation to study the modifications of the hemodynamic response with increasing age. Results are fitted with three macroscopic biophysical models to extract parameters, providing a phenomenological description of vascular and metabolic changes. Our results show that 1) biophysical parameters are estimable from multimodal data and 2) parameter estimates in this population change with aging.

Detection of hemodynamic responses to epileptic activity using simultaneous Electro-EncephaloGraphy (EEG)/Near Infra Red Spectroscopy (NIRS) acquisitions.

Simultaneous recordings of Electro-EncephaloGraphy (EEG) with Near InfraRed Spectroscopy (NIRS) allow measuring hemodynamic changes (changes in the concentration of oxy- and deoxyhemoglobin) at the time of epileptic discharges detected on scalp EEG. Two NIRS detection methods based on the General Linear Model (GLM) respectively in the time domain and in the time-frequency domain are investigated in this study using realistic simulations of spontaneous interictal epileptic activity. We evaluated the sensitivity at different Signal to Noise Ratios (SNR), the effect of either a large or a small number of discharges and the impact of model misspecification (e.g. omission or false detection of epileptic discharges). We also explored the effect on the estimation of key parameters, which set the model order. Simulations showed that both methods become inaccurate in lower SNR conditions, leading to many false positive detections. However, the time-frequency estimator showed better performance than the time-domain one. Key parameters for each algorithm were identified and results suggest to model confounds in the GLM differently for oxy- and deoxyhemoglobin. We also demonstrated that an inaccurate marking of epileptic events has a small impact on the detection statistics whereas an inaccurate specification of the hemodynamic response function delay decreases drastically the detection abilities. Finally, we illustrated the two methods on clinical EEG/NIRS data of one patient with focal epilepsy, showing an increase of regional Cerebral Blood Volume (rCBV) spatially concordant with the presumed epileptogenic focus.

Validity of occupational stress assessment using a visual analogue scale.

BACKGROUND: The visual analogue scale (VAS) is empirically used by occupational physicians to assess stress but very few studies have been published about its quantitative validation. AIMS: To assess the external validity of the VAS for the assessment of stress in the clinical occupational health setting by comparing its scores with the Perceived Stress Scale (PSS) of Cohen. METHODS: An anonymous self-completed questionnaire (PSS14) and the VAS were filled in by a random sample of 360 workers from several occupational health centres. RESULTS: No difference between the mean scores of PSS14 and stress VAS was found. The equation of the linear regression was 'VAS score = -0.18 + 1008 × PSS14 score'. A VAS score of 7.0 was identified as having the best sensitivity/specificity ratio (0.74 and 0.93, respectively) for identifying those with 'high stress' using the PSS cut-off score of 7.2, using a receiver operator curve approach. CONCLUSIONS: Our results support an acceptable agreement between the two tests, meaning that the two tools assess the same psychological construct. The good sensitivity/specificity ratio and the area under the curve close to 1 provide evidence that a VAS is suitable to help the occupational physician detect a high level of stress. The use of a VAS for stress assessment seems to be meaningful, suitable and useful for occupational physicians.

Bimodal modulation and continuous stimulation in optical imaging to map direction selectivity.

In the visual system, neurons with similar functional properties such as orientation and direction selectivity are clustered together to form modules. Optical imaging recordings in combination with episodic paradigms have been previously used to estimate direction selectivity, a fundamental property of visual neurons. The major drawback of the episodic approach is that the extraction of the signal from various forms of physiological noise is difficult, leading to a poor estimation of direction. Recent work, based on periodic stimulation and Fourier decomposition improved the extraction of periodic stimulus responses from noise and thus, reduced the recording time considerably. Given the success of this new paradigm in mapping orientation, the present study evaluated its reliability to measure direction selectivity in the visual cortex of anesthetized cats. Here, a model that exploits the harmonics of the Fourier decomposition is proposed where the first harmonic is related to direction responses, and the second to orientation. As expected, the first harmonic was absent when a static stimulus was presented. Contrarily, the first harmonic was present when moving stimuli were presented and the amplitude was greater with random dots kinematograms than with drifting gratings. The phase of the first harmonic showed a good agreement with direction preference measured by episodic paradigm. The ratio of the first/the second harmonic amplitude, related to a direction index, was weaker in fracture. It was also weaker in areas of the ventral pathway (areas 17 and 21a) where direction selectivity is known to be reduced. These results indicate that a periodic paradigm can be easily used to measure specific parameters in optical signals, particularly in situations when short acquisition periods are needed.

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.

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.

Nonbacterial purpura fulminans and severe autoimmune acquired protein S deficiency associated with human herpesvirus-6 active replication.

Nonbacterial purpura fulminans (PF) is rare, usually follows viral infection in young children, and is characterized by specific coagulation disorders, requiring specific therapy. Following a transient rash, a 2-year-old previously healthy girl developed PF without haemodynamic impairment. Laboratory data revealed disseminated intravascular coagulation and a severe transient protein S deficiency. Antiprotein S autoantibodies and active human herpesvirus-6 (HHV6) replication were demonstrated. Purpuric skin lesions spread very rapidly despite broad-spectrum antibiotics and right leg amputation. Plasmapheresis and intravenous immunoglobulins gave complete clinical recovery and normalization of protein S level within 10 days, with progressive clearance of antiprotein S autoantibodies. Transient severe protein S deficiencies have previously been reported in patients with nonbacterial PF, usually after varicella infection. This is the first documented case of PF after HHV6 infection.

RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca(2+) channels.

Ca(2+) influx through voltage-gated channels initiates the exocytotic fusion of synaptic vesicles to the plasma membrane. Here we show that RIM binding proteins (RBPs), which associate with Ca(2+) channels in hair cells, photoreceptors, and neurons, interact with alpha(1D) (L type) and alpha(1B) (N type) Ca(2+) channel subunits. RBPs contain three Src homology 3 domains that bind to proline-rich motifs in alpha(1) subunits and Rab3-interacting molecules (RIMs). Overexpression in PC12 cells of fusion proteins that suppress the interactions of RBPs with RIMs and alpha(1) augments the exocytosis triggered by depolarization. RBPs may regulate the strength of synaptic transmission by creating a functional link between the synaptic-vesicle tethering apparatus, which includes RIMs and Rab3, and the fusion machinery, which includes Ca(2+) channels and the SNARE complex.

Inner ear defects induced by null mutation of the isk gene.

The isk gene is expressed in many tissues. Pharmacological evidence from the inner ear suggests that isk mediates potassium secretion into the endolymph. To examine the consequences of IsK null mutation on inner ear function, and to produce a system useful for examining the role(s) IsK plays elsewhere, we have produced a mouse strain that carries a disrupted isk locus. Knockout mice exhibit classic shaker/waltzer behavior. Hair cells degenerate, but those of different inner ear organs degenerate at different times. Functionally, we show that in mice lacking isk, the strial marginal cells and the vestibular dark cells of the inner ear are unable to generate an equivalent short circuit current in vitro, indicating a lack of transepithelial potassium secretion.

Complex wavelets applied to diffuse optical spectroscopy for brain activity detection.

The analysis of diffuse optical imaging (DOI) data has seen significant developments over the last few years. When compared to fMRI, signals originating from optical imaging are tainted by more physiology and the separation of activation from this background can be difficult in some cases. In this work, we show that the use of time-frequency techniques based on wavelets distinguish different physiological sources from the evoked response to a given stimulus. In particular, we show that analytical complex wavelets identify synchronies in the signal at different scales. These synchronies are then used to extract activation information from the DOI data in order to estimate the evoked hemodynamic response or to define a new type of contrast between two conditions. This work presents both simulations and applications with real data (visual stimulation and motor tasks experiments).

Inhalational anesthetics activate two-pore-domain background K+ channels.

Volatile anesthetics produce safe, reversible unconsciousness, amnesia and analgesia via hyperpolarization of mammalian neurons. In molluscan pacemaker neurons, they activate an inhibitory synaptic K+ current (IKAn), proposed to be important in general anesthesia. Here we show that TASK and TREK-1, two recently cloned mammalian two-P-domain K+ channels similar to IKAn in biophysical properties, are activated by volatile general anesthetics. Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK. Carboxy (C)-terminal regions were critical for anesthetic activation in both channels. Thus both TREK-1 and TASK are possibly important target sites for these agents.

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.