Low thoracic skeletal muscle index is associated with negative outcomes in 244 patients with respiratory COVID-19.

BACKGROUND: Sarcopenia is associated with negative outcomes in intensive care unit (ICU) patients and during chronic diseases. We aimed to evaluate if low skeletal muscle index (SMI) measured by computed tomography (CT) at the thoracic level is associated with poor outcomes in hospitalized patients with respiratory COVID-19. METHODS: Patients admitted to the hospital between March 1st and June 9, 2020 with a confirmed diagnosis of respiratory COVID-19 in the Emergency Department were included in this retrospective cohort study. SMI was assessed from a transverse CT image at the T12 level. We analysed the association between thoracic SMI and mortality, ICU admissions, infections, length of stay and gravity scores. RESULTS: We included 244 patients, whose median age was 62 (20-95) years, mean body mass index was 28,6 kg/m2, and 34% were obese patients. 102 patients (41,8%) had low thoracic SMI. On multivariable analysis, low thoracic SMI was associated with more infections (OR = 1,88 [1,06-2,98]) and increased length of stay (OR = 1,87 [1,14-3,49]) but not with mortality (OR = 1.37 [0.54-3.52]), whereas it was inversely associated with ICU admission (OR = 5,56 [1,96-16,67]. CONCLUSION: Low SMI measured by CT at the thoracic level T12 is associated with negative outcomes in patients with respiratory COVID-19.

Mental health among university students with eating disorders and irritable bowel syndrome in France.

BACKGROUND: University students are subject to stress due to academic pressure, empowerment and transition from adolescence to adulthood. This young population may have a higher risk of functional disorders as eating disorders (ED) and irritable bowel syndrome (IBS). Our objective was to determine the prevalence of ED, IBS and both and the associated behaviours. METHODS: A cross sectional study was conducted in Rouen University (France). Participating students filled an anonymous self-questionnaire with items on socio-demographics, depression (Duke score), stress (Cohen score), emotional exhaustion (Maslach Inventory), insomnia (Insomnia Severity Index), cyberaddiction (Internet Addiction Test), ED (SCOFF-F test) and IBS (Rome III). RESULTS: This study included 731 students (male/female ratio=0.43). The prevalences of ED, IBS and co-existing ED-IBS were respectively 16.7%, 7.8% and 2.7%. ED and IBS were more common in female students. Depression, stress, emotional exhaustion, insomnia and cyberaddiction were significantly associated with ED and IBS or both. Students with ED had a higher risk of having IBS (Adjusted Odds Ratio (AOR)=2.42, 95% CI: 1.30-4.51), and conversely students with IBS had a higher risk of having ED (AOR=2.46, 95% CI: 1.32-4.55) and were more likely to be in the third year of academic study or above (AOR=2.95, 95% CI: 1.50-5.76). CONCLUSION: Students (female especially) suffer from ED and IBS, with a significant risk of co-existing ED-IBS. ED and IBS are related to multiple mental health symptoms, which could lead to negative academic consequences. Screening, using simple and quick tests as SCOFF questionnaire and ROME IV criteria (update of ROME III in 2016), is essential in this population of university students.

Changes and specificities in health behaviors among healthcare students over an 8-year period.

BACKGROUND: Healthcare students are future health care providers and serve as role models and coaches to enhance behaviors for healthy lifestyles. However healthcare students face multiple stressors that could lead to adopting risk behaviors. OBJECTIVES: To assess the changes in health risk factors among healthcare students between 2007 and 2015, and to identify specific health behaviors based on the curriculum in a population of healthcare students. METHODS: Two cross sectionnal studies were conducted in 2007 and 2015 among nursing, medical, pharmacy, and physiotherapy students (Rouen, France). During compulsory courses and examination sessions students filled self-administered questionnaires on socio-demographic characteristics and behavior as: tobacco smoking, alcohol consumption, cannabis consumption, eating disorders, regular practice of sport, perceived health, stress and use of psychotropic drugs. RESULTS: 2,605 healthcare students were included (1,326 in 2007 and 1,279 in 2015), comprising 1,225 medical students (47.0%), 738 nursing students (28.3%), 362 pharmacy students (13.9%), and 280 physiotherapy students (10.8%). Between 2007 and 2015, occasional binge drinking and regular practice of sport increased significantly among healthcare students, respectively AOR = 1.48 CI95% (1.20-1.83) and AOR = 1.33 CI95% (1.11-1.60), regular cannabis consumption decreased significantly, AOR = 0.32 CI95% (0.19-0.54). There was no change in smoking or overweight/obese. There was a higher risk of frequent binge drinking and a lower risk of tobacco smoking in all curricula than in nursing students. Medical students practiced sport on a more regular basis, were less overweight/obese, had fewer eating disorders than nursing students. CONCLUSION: Our findings demonstrate a stable frequency of classic behaviors as smoking but a worsening of emerging behaviors as binge drinking among healthcare students between 2007 and 2015. Health behaviors differed according to healthcare curricula and nursing students demonstrated higher risks. As health behaviors are positively related to favorable attitudes towards preventive counseling, therefore healthcare students should receive training in preventive counseling and develop healthy lifestyles targeted according to the health curriculum.

Delayed gastric emptying and altered antrum protein metabolism during activity-based anorexia.

BACKGROUND: Anorexia nervosa, a restrictive eating disorder, is often associated with gastrointestinal disorders, particularly a delayed gastric emptying. However, the mechanisms remained poorly documented. Thus, we aimed to evaluate gastric emptying and antrum protein metabolism in the Activity-Based Anorexia model (ABA). METHODS: Females C57Bl/6 mice were randomized into 3 groups: Control, ABA, and Limited Food Access (LFA). Food access has been progressively limited from 6 h/day at day 6 to 3 h/day at day 9 and until day 17. ABA mice had free access to an activity wheel. Gastric emptying was assessed. On gastric extracts, a proteomic analysis was performed, as well as an evaluation of protein synthesis and protein oxidation. KEY RESULTS: Both LFA and ABA mice exhibited a delayed gastric emptying compared with Controls (P < .05). Proteomic approach revealed 15 proteins that were differentially expressed. Among these proteins, we identified 2 clusters of interest contributing to (i) the organization of muscle fiber with ACTA2, VCL, KRT19, KRT8, and DES proteins and (ii) "heat shock proteins" with STIP1, HSPD1, and HSPA8 proteins. ABA mice specifically exhibited an increased rate of gastric oxidized proteins. CONCLUSIONS AND INFERENCES: Delayed gastric emptying observed in anorectic conditions appears to be secondary to malnutrition. However, an oxidative stress is specifically present in the stomach of ABA mice. Its role remains to be further studied.

Hemoperitoneum in peripartum: A case-series.

Hemorrhages are the first cause of perinatal deaths in French women. Thirteen percent of these deaths are not linked to obstetrical problems but rather to hemoperitoneum. These incidents are under-diagnosed and as a result, treatment is delayed and fetal and maternal mortality increases. We report three cases of patients, all White female in their last trimester of a non-problematic pregnancy presenting with hemoperitoneum and resulting in different outcomes. The analysis of published materials and of our cases leads us to infer that a diagnosis of hemoperitoneum must be considered in pregnant women when abdominal pain, symptoms of shock and a decrease in hemoglobin are associated. An immediate response and intensive care followed by hemostatic surgery give these patients the best chance to survive.

Acute sacral nerve stimulation reduces visceral mechanosensitivity in a cross-organ sensitization model.

BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model. METHODS: Hypersensitive model was obtained by instillation of acetic acid into the bladder of rats during 5 minutes, 30 minutes before the start of the experiments. Visceral sensitivity was assessed by monitoring the change in mean arterial pressure in response to graded isobaric colorectal distension series. To decipher the mechanisms underlying SNS effect, rats were administered intravenously either a nonselective opioid receptor antagonist (naloxone) or a nitric oxide synthesis antagonist (L-NAME). Neuronal activation in the dorsal horn of the sacral spinal cord was measured by counting c-fos immunoreactive cells in response to colorectal distension and NMS. KEY RESULTS: Intravesical acetic acid instillation increased mean arterial pressure variation in response to colorectal distension when compared to saline group. SNS reduced the variation in arterial pressure. Colorectal distension induced a rise in c-fos immunoreactive cells in the dorsal horn of the spinal cord. This effect was reduced by SNS. CONCLUSIONS & INFERENCES: SNS reduces visceral mechanosensitivity in a cross-organ sensitization model.

A specific prediction equation is necessary to estimate peak oxygen uptake in obese patients with metabolic syndrome.

PURPOSE: The aims were to: (1) compare peak oxygen uptake ([Formula: see text]peak) predicted from four standard equations to actual [Formula: see text]peak measured from a cardiopulmonary exercise test (CPET) in obese patients with metabolic syndrome (MetS), and (2) develop a new equation to accurately estimate [Formula: see text]peak in obese women with MetS. METHODS: Seventy-five obese patients with MetS performed a CPET. Anthropometric data were also collected for each participant. [Formula: see text]peak was predicted from four prediction equations (from Riddle et al., Hansen et al., Wasserman et al. or Gläser et al.) and then compared with the actual [Formula: see text]peak measured during the CPET. The accuracy of the predictions was determined with the Bland-Altman method. When accuracy was low, a new prediction equation including anthropometric variables was proposed. RESULTS: [Formula: see text]peak predicted from the equation of Wasserman et al. was not significantly different from actual [Formula: see text]peak in women. Moreover, a significant correlation was found between the predicted and actual values (p < 0.001, r = 0.69). In men, no significant difference was noted between actual [Formula: see text]peak and [Formula: see text]peak predicted from the prediction equation of Gläser et al., and these two values were also correlated (p = 0.03, r = 0.44). However, the LoA95% was wide, whatever the prediction equation or gender. Regression analysis suggested a new prediction equation derived from age and height for obese women with MetS. CONCLUSIONS: The methods of Wasserman et al. and Gläser et al. are valid to predict [Formula: see text]peak in obese women and men with MetS, respectively. However, the accuracy of the predictions was low for both methods. Consequently, a new prediction equation including age and height was developed for obese women with MetS. However, new prediction equation remains to develop in obese men with MetS.

Validation of the Arabic version of the SCOFF questionnaire for the screening of eating disorders.

The high prevalence of eating disorders in Arab countries indicates a need for an Arabic language screening tool. This study aimed to validate an Arabic version (A-SCOFF) of the British SCOFF questionnaire, a brief tool for the screening of eating disorders in primary health care. After translation and back-translation the A-SCOFF was given to 123 female patients [mean age 32 (SD 8.8) years] visiting primary health-care centres in Beirut. Each patient was evaluated by an eating disorders specialist blinded to A-SCOFF results. The validated Arabic version of the Mini International Neuropsychiatric Interview and the DSM-IV criteria for eating disorders were used as diagnostic references. The best diagnostic threshold for the A-SCOFF was found to be at 2 positive answers with a sensitivity of 80.0%, a specificity of 72.7% and an area under the curve of 80.0%. The A-SCOFF questionnaire is accurate and reliable for the early detection of eating disorders in this high-risk population.

Impact of deep brain stimulation on pharyngo-esophageal motility: a randomized cross-over study.

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinson's disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study. METHODS: Sixteen humans PD patients (4 women, 12 men; age: 62.4 ± 9.3-years old) who underwent STN stimulation for at least 6 months were randomly evaluated with either stimulator turned OFF then ON, or inversely. Esophageal high resolution manometry was performed at the end of each ON and OFF period, with a 5 min resting period followed by ten swallows of 5 mL. KEY RESULTS: During the ON, an increase in the distal contractility index was found (OFF: 1750 ± 629 vs ON: 2171 ± 755 mmHg/cm/s; p = 0.03), with no difference in the distal front velocity. A decrease in the integrative relaxation pressure of the lower esophageal sphincter (LES) was noted (OFF: 11.1 ± 1.8 mmHg vs ON: 7.2 ± 1.8 mmHg; p < 0.05) in ON. The LES resting pressure remained unchanged during the two periods. This resulted in a decrease in the intrabolus pressure (p = 0.03). No difference was observed for the upper esophageal sphincter, nor the pharyngeal contraction amplitude and velocity. CONCLUSIONS & INFERENCES: In conclusion, STN stimulation in PD patients increased esophageal body contractions and enhanced the LES opening. This suggests that the nigrostriatal-striatonigral loop is involved in the control of esophageal motility.

Acute sacral nerve stimulation reduces visceral mechanosensitivity in Rat through spinal opioid pathway.

BACKGROUND: Sacral nerve stimulation (SNS) is an alternative surgical treatment of refractory urge incontinence and/or fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS remain poorly understood. The aim of this experimental study was to evaluate the effect of SNS on visceral mechanosensitivity in rats. METHODS: Anesthetized Sprague-Dawley rats were treated with SNS or sham stimulation. SNS was performed by implanting an electrode close to the sacral nerve root S1. Rats were administered either a non-selective opioid receptor antagonist (naloxone) or a nitric oxide synthase inhibitor (L-NAME). Colonic mechanosensitivity was evaluated using the variation of arterial blood pressure as a spino-bulbar reflex in response to graded isobaric colorectal distension (CRD). C-fos immunoreactive neurons were quantified in spinal and supraspinal sites. µ-opioid receptor (MOR) internalization was counted in the sacral spinal cord with sham or effective SNS in response to CRD. KEY RESULTS: SNS reduced visceral mechanosensitivity in response to CRD. This effect was reversed by intrathecal and intraveinous naloxone administration. In both models, CRD induced increased c-fos immunoreactivity in the dorsal horn neurons of the sacral spinal cord and supraspinal areas. This increase was prevented by SNS. MOR internalization was significantly higher in stimulated group. CONCLUSIONS & INFERENCES: SNS impacts on visceral mechanosensitivity by decreasing the spino-bulbar reflex in response to CRD. Spinal opioid receptors are likely involved in this effect.

Chronic delivery of α-melanocyte-stimulating hormone in rat hypothalamus using albumin-alginate microparticles: effects on food intake and body weight.

Chronic delivery of neuropeptides in the brain is a useful experimental approach to study their long-term effects on various biological parameters. In this work, we tested albumin-alginate microparticles, as a potential delivery system, to study if continuous release in the hypothalamus of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, may result in a long-term decrease in food intake and body weight. The 2-week release of α-MSH from peptide-loaded particles was confirmed by an in vitro assay. Then, daily food intake and body weight were studied for 18 days in rats injected bilaterally into the paraventricular hypothalamic nucleus with particles loaded or not with α-MSH. A decrease in body weight gain, persisting throughout the study, was found in rats injected with α-MSH-charged particles as compared with rats receiving non-charged particles and with rats injected with the same dose of α-MSH in solution. Food intake was significantly decreased for 3 days in rats receiving α-MSH-loaded particles and it was not followed by the feeding rebound effect which appears after food restriction. The presence of α-MSH-loaded particles in the hypothalamus was confirmed by immunohistochemistry. In conclusion, our study validates albumin-alginate microparticles as a new carrier system for long-term delivery of neuropeptides in the brain and demonstrates that chronic delivery of α-MSH in the hypothalamus results in a prolonged suppression of food intake and a decrease of body weight gain in rats.

Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders.

The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) are involved in regulation of feeding and emotion; however, the origin of such auto-Abs is unknown. Here, using proteomics, we identified ClpB heat-shock disaggregation chaperone protein of commensal gut bacteria Escherichia coli as a conformational antigen mimetic of α-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with α-MSH, influencing food intake, body weight, anxiety and melanocortin receptor 4 signaling. Furthermore, chronic intragastric delivery of E. coli in mice decreased food intake and stimulated formation of ClpB- and α-MSH-reactive antibodies, while ClpB-deficient E. coli did not affect food intake or antibody levels. Finally, we show that plasma levels of anti-ClpB IgG crossreactive with α-MSH are increased in patients with AN, bulimia and BED, and that the ED Inventory-2 scores in ED patients correlate with anti-ClpB IgG and IgM, which is similar to our previous findings for α-MSH auto-Abs. In conclusion, this work shows that the bacterial ClpB protein, which is present in several commensal and pathogenic microorganisms, can be responsible for the production of auto-Abs crossreactive with α-MSH, associated with altered feeding and emotion in humans with ED. Our data suggest that ClpB-expressing gut microorganisms might be involved in the etiology of EDs.

Morphological and immunohistochemical study of ovarian and tubal dysplasia associated with tamoxifen.

Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies for BReast CAncer gene (BRCA) mutation. Similar histopathological abnormalities have been revealed after ovulation stimulation. Given that tamoxifen (TAM) has a clomid-like effect and is sometimes used to induce ovulation, we studied the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in adnexectomies previously exposed to TAM for breast cancer. We blindly reviewed 173 histopathological slides of adnexectomies according to three groups - oophorectomie sassociated with TAM exposure (n=42), oophorectomies associated with clomiphene exposure (n=15) and a spontaneously fertile non cancerous control group (n=116). Morphological features (with an ovarian and tubal dysplasia scoring system) and immunohistochemical expression patterns of Ki-67, p53 and Aldehyde dehydrogenase 1 (ALDH1 is an enzyme significantly associated with earlystage ovarian cancer) were evaluated and correlated. Mean tubal dysplasia score was significantly higher in the TAM group and clomiphene group than in controls (respectively 7.8 vs 3.5, P<0.007 and 6.8 vs 3.5, P=0.008). There is no statistical difference for the ovarian score in TAM group in comparison with the control group whereas we found a significant score for clomiphen group (6.5, P=0.009). Increased ALDH1 expression was observed in the two exposed group whereas expression patterns of Ki67 and p53 were moderate. Interestingly, ALDH1 expression was low in non-dysplastic epithelium, high in dysplasia, and constantly low in the two carcinoma. Furthermore, we confirm our previous results showing that ALDH1 may be a useful tissue biomarker in the subtle histopathological diagnosis of tubo-ovarian dysplasia.

Is BRAF a prognostic factor in stage III skin melanoma? A retrospective study of 72 patients after positive sentinel lymph node dissection.

BACKGROUND: BRAF was identified as an oncogene in skin melanoma in 2002, and since 2011 has been a therapeutic target in the treatment of metastatic melanoma. The role of BRAF mutation in tumour initiation and the disease course remains to be elucidated. OBJECTIVES: The main objective of our study was to determine whether there is a relationship between BRAF status and overall survival in patients with a melanoma and a positive sentinel lymph node. We also sought an association between BRAF status and the clinicopathological features of the melanoma. Finally, we looked for a potential heterogeneity of BRAF status in primary and metastatic tumours. METHODS: All patients (n = 72) treated for melanoma and with a positive sentinel lymph node at the University Hospital of Clermont-Ferrand, France, between January 2000 and January 2010 were enrolled in the study. We investigated BRAF status in primary melanoma and lymph node metastatic tissue in our molecular pathology laboratory and collected the clinical and survival data. RESULTS: Of the 72 patients, 32 had at least one BRAF mutation. There was a statistically significant difference in overall survival between the BRAF-mutated and wild-type populations. The only clinical feature related to BRAF status was metastatic burden. Of the 25 patients in whom we obtained the status in both locations, five had a discordant result. CONCLUSIONS: BRAF mutation is an indicator of poor prognosis in patients with stage III melanoma with a positive sentinel lymph node. BRAF status could be used in the staging of this population. BRAF has a role not only in cellular immortalization but also in metastatic spread.

A feature selection based framework for histology image classification using global and local heterogeneity quantification.

Biopsy remains the gold standard for the diagnosis of chronic liver diseases. However, the concordance between readers is subject to variability causing an increasing need of objective tissue description methods. A complete framework has been implemented to analyze histological images from any kind of tissue. Based on the feature selection approach, it computes the most relevant subset of descriptors in terms of classification from a wide initial list of local and global descriptors. In comparison with equivalent methods, this implementation is able to find lists of descriptors which are significantly shorter for an equivalent accuracy and furthermore it enables the classification of slides using combinations of global and local measurements. The results have pointed that it could reach an accuracy of 82.8% in a human liver fibrosis grading approach by selecting 6 descriptors from an initial set of 258 global and local descriptors.

[Prenatal diagnosis of cerebral tumors and differential diagnosis]. / Diagnostic anténatal des tumeurs cérébrales fœtales et diagnostics différentiels.

Fetal brain tumors are rare and have different histologies. Although the definitive diagnosis relies on the histopathology of the tumor, it is useful to distinguish the tumors potentially curable from the tumors rapidly fatal after birth. Nevertheless, some intracranial masses are not tumors. We report four cases of intracerebral masses diagnosed prenatally corresponding to different histological lesions: teratoma, fetus-in-fetu, chraniopharyngioma, hemangioma. We discuss the elements of the differential diagnosis, which can be identified prenatally.

Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients.

Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.

Desmoplastic malignant melanoma: a study of ten cases and status of BRAF mutation.

BACKGROUND: Desmoplastic malignant melanoma (DM) is a rare variant of melanoma. BRAF gene mutations have been poorly explored in this entity. OBJECTIVE: To detect BRAF gene mutation in a series of DM. METHODS: This is a single-center retrospective study of ten patients with DM, with a biomolecular analysis of BRAF mutation. RESULTS: The male:female ratio was 2.3:1, with a mean patient age of 66.5 years. Melanoma arose in the head and neck region in 3 cases. The mean tumor thickness was 7.97 mm, Clark level was IV or V in all cases. Six melanomas were of the pure DM variant. Three patients had at least one local recurrence, two had regional node metastases, and two experienced systemic metastases which they died of (average follow-up 34.1 months). A V600E BRAF mutation was detected in only one patient. CONCLUSION: BRAF mutation seems to be a rare event in DM contrary to other melanoma variants.

[Congenital diaphragmatic hernia - mechanisms of pulmonary hypoplasia]. / Hernie congénitale du diaphragme : mécanismes de l'hypoplasie pulmonaire.

Congenital diaphragmatic hernia (CDH) is a common cause of severe neonatal respiratory distress. Mortality and morbidity are determined by the amount of pulmonary hypoplasia (PH) that occurs and by the development of therapy-resistant pulmonary hypertension. The pathogenesis and aetiology of CDH and its associated anomalies are still largely unknown despite all research efforts. The pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. PH, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Our understanding of CDH has also been aided by basic research with the use of dietary, teratogen-induced, and knockout models of CDH. These studies indicate that lung hypoplasia may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. Recent data reveal the role of disruption of a retinoid-signalling pathway in the pathogenesis of CDH. Although multifactorial inheritance may best explain most cases of CDH in humans, much has been learned about the genetic factors that play a role in the development of CDH by studies of patients with CDH caused by specific genetic syndromes and chromosome anomalies. More research is warranted to improve our understanding of normal and abnormal lung development in relation to CDH. Such investigations will help in the design of new treatment strategies to improve the natural course or even to prevent this anomaly.

[A lethal variant of Netherton syndrome in a large inbred family]. / Forme létale de syndrome de Netherton au sein d'une famille multiplex consanguine.

Netherton syndrome is a rare autosomal recessive disorder characterized by the triad of ichthyosiform erythrodermia, typical hair dysplasia, and severe atopic features. The broad range of variable expression of this disease is well described and 20% of complications occur during the neonatal period such as hypernatremic dehydration, electrolyte imbalances, recurrent or severe infections, and failure to thrive. Mutation of the SPINK5 gene has been identified as disease-causing in Netherton syndrome, but the pathophysiology still remains unclear. Almost all SPINK5 mutations result in the absence of the serine-protease inhibitor LEKTI protein in both keratinocytes and lymphocytes. In this study, we report on a severe form of Netherton syndrome observed in three patients within a large inbred Rom family. All of them died in the first months of life despite early treatment. They were found to be homozygous for the c.1431-12G>A SPINK5 gene mutation, which has not been associated with a lethal form of the disease thus far. This family illustrates the extreme phenotype of Netherton disease of neonatal onset. Molecular diagnosis allowed further genetic counseling and prenatal testing during other pregnancies.