Effect of Extrinsic and Intrinsic Stressors on Clinical Skills Performance in Third-Year Medical Students.

BACKGROUND: Both enhancements and impairments of clinical performance due to acute stress have been reported, often as a function of the intensity of an individual's response. According to the broader stress literature, peripheral or extrinsic stressors (ES) and task-contingent or intrinsic stressors (IS) can be distinguished within a stressful situation. The objective of this study was to assess the impact of IS and ES on clinical performance. METHOD: A prospective randomized crossover study was undertaken with third-year medical students conducting two medical experiences with simulated patients. The effects of severity of the disease (IS) and the patient's aggressiveness (ES) were studied. A total of 109 students were assigned to four groups according to the presence of ES and IS. Subjective stress and anxiety responses were assessed before and after each experience. The students' clinical skills, diagnostic accuracy and argumentation were assessed as clinical performance measures. Sex and student-perceived cognitive difficulty of the task were considered as adjustment variables. RESULTS: Both types of stressors improved clinical performance. IS improved diagnostic accuracy (regression parameter ß = 9.7, p = 0.004) and differential argumentation (ß = 5.9, p = 0.02), whereas ES improved clinical examination (ß = 12.3, p < 0.001) and communication skills (ß = 15.4, p < 0.001). The student-perceived cognitive difficulty of the task was a strong deleterious factor on both stress and performance. CONCLUSION: In simulated consultation, extrinsic and intrinsic stressors both have a positive but different effect on clinical performance.

Activation of the prostaglandin D2 metabolic pathway in Crohn's disease: involvement of the enteric nervous system.

BACKGROUND: Recent works provide evidence of the importance of the prostaglandin D2 (PGD2) metabolic pathway in inflammatory bowel diseases. We investigated the expression of PGD2 metabolic pathway actors in Crohn's disease (CD) and the ability of the enteric nervous system (ENS) to produce PGD2 in inflammatory conditions. METHODS: Expression of key actors involved in the PGD2 metabolic pathway and its receptors was analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in colonic mucosal biopsies of patients from three groups: controls, quiescent and active CD patients. To determine the ability of the ENS to secrete PGD2 in proinflammatory conditions, Lipocalin-type prostaglandin D synthase (L-PGDS) expression by neurons and glial cells was analyzed by immunostaining. PGD2 levels were determined in a medium of primary culture of ENS and neuro-glial coculture model treated by lipopolysaccharide (LPS). RESULTS: In patients with active CD, inflamed colonic mucosa showed significantly higher COX2 and L-PGDS mRNA expression, and significantly higher PGD2 levels than healthy colonic mucosa. On the contrary, peroxysome proliferator-activated receptor Gamma (PPARG) expression was reduced in inflamed colonic mucosa of CD patients with active disease. Immunostaining showed that L-PGDS was expressed in the neurons of human myenteric and submucosal plexi. A rat ENS primary culture model confirmed this expression. PGD2 levels were significantly increased on primary culture of ENS treated with LPS. This production was abolished by AT-56, a specific competitive L-PGDS inhibitor. The neuro-glial coculture model revealed that each component of the ENS, ECG and neurons, could contribute to PGD2 production. CONCLUSIONS: Our results highlight the activation of the PGD2 metabolic pathway in Crohn's disease. This study supports the hypothesis that in Crohn's disease, enteric neurons and glial cells form a functional unit reacting to inflammation by producing PGD2.

[Dual role for prostaglandin D2 in intestinal epithelial homeostasis]. / Prostaglandine D2 et homéostasie de la barrière épithéliale intestinale--Une relation équivoque.

Prostaglandin D2 (PGD2) and derivatives are lipid mediators involved in the control of the intestinal epithelial barrier homeostasis. Their involvement in the pathophysiology of chronic inflammatory bowel disease (IBD) is still debated. Several results highlight the duality of PGD2 as an anti- or pro-inflammatory mediator. This duality seems to be related to a differential expression of its receptors by intestinal epithelial cells and the surrounding immunocompetent cells. The enteric glial cells from the enteric nervous system (ENS) express the lipocalin-type-prostaglandin D synthase and secrete PGD2 and 15d-PGJ2. The protective role of the ENS in the homeostatic control of the epithelial intestinal barrier and its involvement in the pathogenesis of IBD have already been demonstrated. Thus, these lipid mediators seem to be new actors of the neuro-glio-epithelial unit and could play a crucial role maintaining gut barrier integrity.

Stress responses in medical students in ambulatory and in-hospital patient consultations.

CONTEXT: Little is known about health professionals' responses to acute stressors encountered in the clinical environment. The goal of this study was to measure the subjective and physiological stress responses of medical students to consultations in familiar (in-hospital) and unfamiliar (ambulatory) settings. We hypothesised that: (i) providing a consultation in an unfamiliar setting would result in increased stress responses in medical students, and (ii) some differences in stress responses according to gender might become apparent. METHODS: A quantitative cross-over study was conducted over a 6-month period. Participating students were invited to provide consultations to patients in an ambulatory setting. In order to provide a control condition, each student was required to conduct a similar consultation (without reporting back to the patient) with an in-hospital patient during his or her rotation in internal medicine. Pre- and post-consultation subjective and physiological responses were measured using a visual analogue scale (VAS), the State-Trait Anxiety Inventory (STAI), a cognitive appraisal scale and salivary cortisol levels. RESULTS: All of the subjective and physiological stress responses were greater in the ambulatory setting than the in-hospital setting. There was an effect of gender on the responses. Women showed greater pre-consultation subjective stress levels in the ambulatory setting, whereas men exhibited greater physiological stress levels in the ambulatory setting. No correlations were observed between subjective and cortisol responses. CONCLUSIONS: Ambulatory consultations are more stressful for medical students than consultations carried out in the more familiar in-hospital setting. Further studies should be conducted to investigate the nature of the stressors in this particular environment, to explore the possible explanations for a gender effect, and to explore the effects of these stress responses on students' diagnostic skills.

Efficiency of the Therascreen® RGQ PCR kit for the detection of EGFR mutations in non-small cell lung carcinomas.

BACKGROUND: Activating mutations of the EGFR gene in lung carcinoma are associated with response to tyrosine kinase inhibitors. Therefore, a rapid, sensitive assay for mutation detection using routine pathological specimens is mandatory in clinical practice. METHODS: We have compared our in-house procedure to the Therascreen® EGFR RGQ PCR kit (Qiagen). This assay, based on allele-specific amplification, is approved in the United States, in Europe, Japan and China. RESULTS: We first selected a series of 209 that were representative of our routine practice during the last 2years. Using our assays, EGFR mutations were detected in 36 (17.4%) of these patients (18 p.L858R mutations and 18 exon 19 deletions). All these alterations were also detected using the Therascreen® kit. In addition, this kit allowed us to detect 7 additional alterations: one exon 19 alteration (c.2239_2240TT>CC, p.L747P), 3 p.G719X mutations and 3 p.S768L mutations. In the second part of our study, we selected 81 samples that were identified as deleted for exon 19 using our assay. Eighteen different deletions were described following sequencing. All these samples were tested positive with the Therascreen® kit. CONCLUSION: The Therascreen® EGFR RGQ kit was found to be very powerful (sensitivity 100%; specificity 100%) for the detection of the most frequent EGFR alterations that are clearly associated with response to tyrosine kinase inhibitors.

[Hormonal evaluation of adrenal incidentalomas]. / Explorations hormonales d'un incidentalome surrénalien.

Imaging technological advances and widespread use of abdominal imaging have led to the identification of an increasing number of adrenal incidentalomas in the last decades. Causes of these adrenal masses are multiple, but the most common etiology is the non-functional adenoma. Although in most cases, these masses are benign and non-functional, clinicians have to perform biochemical testing for subclinical cushing's syndrome, pheochromocytoma or primary hyperaldosteronism. This screening is essential for their etiological diagnosis and therapeutic management. We report in this article the biological approach to detect secretory activity of adrenal incidentalomas and the diagnostic accuracy of the biochemical tests used.

Detection of EGFR gene mutations in non-small cell lung cancer: lessons from a single-institution routine analysis of 1,403 tumor samples.

Activating mutations of the epidermal growth factor receptor (EGFR) in lung tumors are associated with a dramatic response to tyrosine kinase inhibitors. Therefore, routine analysis of pathological specimens is mandatory in clinical practice. We have prospectively tested tumors from Caucasian lung tumor patients between January 2010 and June 2012. DNA was extracted from formalin-fixed paraffin-embedded tissues following macrodissection. The p.L858R substitution was assessed by allele-specific PCR and exon 19 deletions by PCR and DNA fragment analysis. Using a robust process from patient sampling to screening methods, we analyzed samples from 1,403 patients. The EGFR status could be successfully determined for 1,322 patients. EGFR mutations were detected in 179 (13.5%) patients, with female and adenocarcinoma histology predominance. Mutated patients were significantly older than non-mutated patients. Similar mutation rates were obtained with primary tumors and metastases, and with surgical resection, bronchial biopsies, CT-guided needle biopsies and transbronchial needle aspiration. The sensitivity of our assays allowed us to detect EGFR mutations in samples poor (<10%) in tumor cells. Finally, the mutation rate was much higher in tumors expressing the TTF-1 antigen (145/820; 17.7%) than in TTF-1 negative tumors (3/218; 1.4%). The results obtained through routine analysis of more than 1,300 samples indicated that all types of specimen can be analyzed without any significant bias. TTF-1 immunostaining may be used to predict negative EGFR mutation status.

Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas.

Previous studies have identified mutations of the isocitrate dehydrogenase 1 (IDH1) gene in more than 70% of World Health Organization (WHO) grade II and III gliomas. The most frequent mutation leads to a specific amino acid change from arginine to histidine at codon 132 (c.395G>A, p.R132H). IDH1 mutated tumors have a better prognosis than IDH1 non-mutated tumors. The aim of our study was to evaluate and compare the methods of mIDH1 R132H immunohistochemistry, allele-specific PCR and DNA sequencing for determination of IDH1 status. We performed a retrospective study of 91 patients with WHO grade II (n=43) and III (n=48) oligodendrogliomas. A fragment of exon 4 spanning the sequence encoding the catalytic domain of IDH1, including codon 132, was amplified and sequenced using standard conditions. Allele-specific amplification was performed using two forward primers with variations in their 3' nucleotides such that each was specific for the wild-type or the mutated variant, and one reverse primer. Immunohistochemistry was performed with mouse monoclonal mIDH1 R132H. DNA was extracted from FFPE sections following macrodissection. IDH1 mutations were found in 55/90 patients (61.1%) by direct sequencing. R132H mutations were found in 47/55 patients (85.4%). The results of the allele-specific PCR positively correlated with those from DNA sequencing. Other mutations (p.R132C, p.R132S and pR132G) were found by DNA sequencing in 3, 3 and 2 tumors, respectively (8/55 patients, 14.6%). mIDH1 R132H immunostaining was found in the 47 patients presenting the R132H mutation (sensitivity 47/47, 100% for this mutation). None of the tumors presenting a wild-type IDH1 gene were stained (specificity 35/35, 100%). Our results demonstrate that immunohistochemistry using the mIDH1 R132H antibody and allele-specific amplification are highly sensitive techniques to detect the most frequent mutation of the IDH1 gene.