PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory.

Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2MAPK signaling cascade strengthens memory. When stress is particularly intense, very high levels of glucocorticoid hormones then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. PAI-1 levels after trauma could be a predictive biomarker of the subsequent appearance of PTSD and pharmacological inhibition of PAI-1 activity a new therapeutic approach to this debilitating condition.

Neurodevelopmental outcome at 2 years of corrected age in fetuses with increased nuchal translucency thickness and normal karyotype compared with matched controls.

OBJECTIVES: Increased nuchal translucency (NT) thickness is an antenatal marker of aneuploidy or malformation that can lead to termination of pregnancy. This study assessed the long-term neurodevelopmental prognosis of infants who had isolated increased NT in utero. METHODS: This was a prospective cohort study of infants with a NT thickness > 95th percentile in the first trimester, but with a normal karyotype and no major anomalies, and controls with normal NT matched for birth weight, Apgar score, place of birth, parity and gestational age at birth. At 2 years of corrected age, all infants underwent the psychometric Brunet-Lézine test to evaluate their developmental quotient (DQ), overall (global) and specifically for the areas of posture, language, coordination and sociability. RESULTS: A total of 203 chromosomally normal infants were included in the increased-NT group and 208 in the control group. The mean global DQ was significantly lower in the increased-NT group than in the control group (108.6 ± 9.7 vs 112.8 ± 8.3; P < 0.0001), but it was within the normal range expected for that age in both groups. Similarly, the mean DQs for coordination, sociability and language, but not for posture, were significantly lower in infants with increased NT than in controls. Only one case with increased NT had a DQ < 70 (defined as severe neurodevelopmental impairment), compared with none in the control group. The difference between the two groups remained significant for a NT threshold ≥ 99th percentile and when the data were adjusted for NT thickness, the infant's sex and the mother's educational level. In the increased-NT group, NT thickness was < 3.5 mm in over half (56%) of the infants, between 3.5 mm and 5 mm in 33% and > 5 mm in 11%, with a mean global DQ of 108.4, 110.1 and 109.7, respectively. CONCLUSIONS: Infants who had isolated increased fetal NT in the first trimester had a significantly lower, but normal, DQ at a corrected age of 2 years, when compared with controls. The findings were independent of the infant's sex, fetal NT thickness and the mother's educational level. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Heavy precipitation and asthma exacerbation risk among children: A case-crossover study using electronic health records linked with geospatial data.

Extreme precipitation events may be an important environmental trigger for asthma exacerbations in children. We used a time stratified case-crossover design and data from a large electronic health record database at the Children's Hospital of Philadelphia (CHOP) to estimate associations of daily heavy precipitation (defined as > 95th percentile of the summertime distribution) with asthma exacerbation among children. We defined control days as those falling on the same day of the week within the same month and year as the case. We restricted our primary analyses to the summer months in years 2011-2016 and used conditional logistic regression models to estimate associations between heavy precipitation and acute asthma exacerbations in both outpatient (primary care, specialty care, and emergency department) and inpatient settings. We investigated numerous individual-level (e.g., age, sex, eczema diagnosis) and environmental measures (e.g., greenspace, particulate matter) as potential effect modifiers. The analysis include 13,483 asthma exacerbations in 10,434 children. Odds of asthma exacerbation were 11% higher on heavy precipitation vs. no precipitation days (95% CI: 1.02-1.21). There was little evidence of effect modification by most measures. These results suggest that heavy summertime precipitation events may contribute to asthma exacerbations. Further research using larger datasets from other health systems is needed to confirm these results, and to explore underlying mechanisms.

[Optimization of the "pharmaceutical consultation" practiced by pharmacists - Review, feedback and future proposals for development since the introduction of the initiative in 2013 focusing on the Calvados area]. / Optimisation des entretiens pharmaceutiques à l'officine ­ Bilan et retour de cette mission mise en place en 2013 et perspectives de développement dans le département du Calvados.

In 2012, a National Agreement of Pharmacists was initiated in France and then amended in 2013 to introduce the "Pharmaceutical consultation". These consultations must be conducted by the pharmacist with the patient in a confidential area in pharmacy or patient residence. The objective is to decrease the frequency of negative side effects of the medical treatments (anti-vitamins k, direct oral anticoagulants and inhaled corticoid) and to improve the correct use of medication therefore assure the safety of the patient. This initiative also recognizes the expertise of the pharmacists who are remunerated with 50 euros per year and per patient from Social Security. This publication is based on a survey conducted in the whole Calvados area and it is based on several individual interviews. It gives a clear picture about how effective the practice has been so far. It shows that the "Pharmaceutical consultation" is currently only proposed to patients by 40% of pharmacists in this area, additionally the practice decreased by 85% in the pharmacies since 2013. However, 8 on 10 pharmacists recognized a real benefit for patients who subscribed for consultation. Independently, the number of non-subsidized conversation initiatives carried out by pharmacists (anti-tobacco, pregnancy, diabetes) are increasing. This finding leads to the investigation of the causes for not practicing the "Pharmaceutical consultation". The causes for not carrying out the consultations were identified, quantified, analysed and classified with a view to proposing short, medium and long time actions to optimize the "Pharmaceutical consultation" in a financially feasible manner. Nine practical proposals were identified and groups in three areas of improvement: communication, remuneration and organization.

Banff Lung Report: Current knowledge and future research perspectives for diagnosis and treatment of pulmonary antibody-mediated rejection (AMR).

The Lung session of the 2017 14th Banff Foundation for Allograft Pathology Conference, Barcelona focused on the multiple aspects of antibody-mediated rejection (AMR) in lung transplantation. Multidimensional approaches for AMR diagnosis, including classification, histological and immunohistochemical analysis, and donor- specific antibody (DSA) characterization with their current strengths and limitations were reviewed in view of recent research. The group also discussed the role of tissue gene expression analysis in the context of unmet needs in lung transplantation. The current best practice for monitoring of AMR and the therapeutic approach are summarized and highlighted in this report. The working group reached consensus of the major gaps in current knowledge and focused on the unanswered questions regarding pulmonary AMR. An important outcome of the meeting was agreement on the need for future collaborative research projects to address these gaps in the field of lung transplantation.

Can Local Enhancement in Earthworms Affect the Outcome of the Standard Earthworm Avoidance Test?

Earthworms exhibit clumping behaviour in and out of the soil. However, it remains unknown if such social behaviour ultimately influences the outcome of ecotoxicological experiments in the laboratory. We performed several overnight avoidance tests to determine whether social behaviour (i.e., local enhancement) is a factor in pollution avoidance behaviour in the earthworm Eisenia fetida. The results showed that there was no clear influence of social behaviour on the choice or avoidance of Cd contaminated soils, although we suspect that 50 mg Cd/kg might not have been high enough to elicit a significant avoidance response. Nevertheless, when offered a choice between clean undisturbed soil and previously inhabited soil, the worms preferred the previously inhabited soil (p < 0.01). While the level of metal pollution investigated in this study did not disrupt or help predict social dynamics, local enhancement, perhaps driven by some sort of habitat imprinting, was successfully documented in Eisenia fetida.

[The value of healthy skin biopsy in the diagnosis of intravascular B-cell lymphoma: A case report and systematic literature review]. / Intérêt de la biopsie cutanée en peau saine dans le diagnostic du lymphome B intravasculaire : cas clinique et revue systématique de la littérature.

BACKGROUND: Intravascular large B-cell lymphoma (ivLBCL) is a rare blood dyscrasia that is difficult to diagnose. Healthy skin biopsies may prove useful in diagnosis of the condition. Herein we report a case of ivLBCL diagnosed using this type of examination, and we provide a literature review to determine the sensitivity of such testing. PATIENTS AND METHODS: A 67-year-old woman was hospitalised for unexplained prolonged fever (UPF) and impaired general well-being. Laboratory tests revealed inflammatory syndrome, elevated LDH>2000IU/L, hepatic cytolysis and decreased prothrombin time at 47 %. Analysis for infection and medical imaging ruled out both an infectious or inflammatory origin and solid tumour. A healthy skin biopsy enabled confirmation of the diagnosis of ivLBCL. DISCUSSION: This clinical case illustrates the value of healthy skin biopsy in establishing a diagnosis of ivLBCL in patients hospitalised for UPF. Following a systematic literature review in PubMed/Medline, we included eight studies involving at least three patients designed to assess the value of healthy skin biopsy in the diagnosis of ivLBCL. The diagnostic sensitivity of this approach ranged from 67% to 100%, with a sensitivity of 100% being seen in four of the eight studies. Details of the biopsy sites were available in three studies and diagnostic sensitivity was similar overall between samples taken from the thigh, abdomen and arms. CONCLUSION: Healthy skin biopsy sampling from at least two sites constitutes a sensitive and relatively non-invasive procedure for early diagnosis of ivLBCL.

Influence of amino acid sequence in a peptidic Cu+-responsive luminescent probe inspired by the copper chaperone CusF.

Copper(i) is a soft metal ion that plays an essential role in living organisms and Cu+-responsive probes are required to detect Cu+ ions in physiological conditions and understand its homeostasis as well as the diseases associated with its misregulation. In this article, we describe a series of cyclic peptides, which are structurally related to the copper chaperone CusF, and that behave as Cu+-repsonsive probes. These peptide probes comprise the 16-amino acid loop of CusF cyclized by a ß-turn inducer dipeptide and functionalized by a Tb3+ complex for its luminescence properties. The mechanism of luminescence enhancement relies on the modulation of the antenna effect between a tryptophan residue and the Tb3+ ion within the probe when Cu+ forms a cation-π interaction with the tryptophan. Here, we investigate the influence of the amino acid sequence of these cyclic peptides on the copper-induced modulation of Tb3+ emission and show that the rigid ß-turn inducer Aib-d-Pro and insertion of the Tb3+ complex close to its tryptophan antenna are required to obtain turn-on Cu+ responsive probes. We also show that the amino acid sequence, especially the number and position of proline residues has a significant impact on metal-induced luminescence enhancement and metal-binding constant of the probes.

T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-ß. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-ß-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.

TLR3 promotes MMP-9 production in primary human airway epithelial cells through Wnt/ß-catenin signaling.

BACKGROUND: Airway epithelial cells (AEC) act as the first line of defence in case of lung infections. They constitute a physical barrier against pathogens and they participate in the initiation of the immune response. Yet, the modalities of pathogen recognition by AEC and the consequences on the epithelial barrier remain poorly documented. METHOD: We investigated the response of primary human AEC to viral (polyinosinic-polycytidylic acid, poly(I:C)) and bacterial (lipopolysaccharide, LPS) stimulations in combination with the lung remodeling factor Transforming Growth Factor-ß (TGF-ß). RESULTS: We showed a strong production of pro-inflammatory cytokines (Interleukin (IL)-6, Tumor Necrosis Factor α, TNFα) or chemokines (CCL2, CCL3, CCL4, CXCL10, CXCL11) by AEC stimulated with poly(I:C). Cytokine and chemokine production, except CXCL10, was Toll Like Receptor (TLR)-3 dependent and although they express TLR4, we found no cytokine production after LPS stimulation. Poly(I:C), but not LPS, synergised with TGF-ß for the production of matrix metalloproteinase-9 (MMP-9) and fibronectin. Mechanistic analyses suggest the secretion of Wnt ligands by AEC along with a degradation of the cellular junctions after poly(I:C) exposure, leading to the release of ß-catenin from the cell membrane and stimulation of the Wnt/ß-catenin pathway. CONCLUSION: Our results highlight the cross talk between TGF-ß and TLR signaling in bronchial epithelium and its impact on the remodeling process.

The impact of pathogen burden on leukocyte telomere length in the Multi-Ethnic Study of Atherosclerosis.

Several infections have been linked to telomere shortening and in some cases these associations have varied by sex. We assessed the association between seropositivity to four persistent pathogens (cytomegalovirus (CMV), herpes simplex virus-1, Helicobacter pylori, Chlamydia pneumoniae), and total pathogen burden on leukocyte telomere length in a diverse US sample. Data came from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study. We utilized cross-sectional survey data, and biological samples from participants tested for pathogens and telomere length (N = 163). Linear regression was used to examine the association between seropositivity for individual pathogens as well as total pathogen burden and telomere length, adjusting for various confounders. CMV seropositivity and increased total pathogen burden level were significantly associated with shorter telomere length among females (ß = -0·1204 (standard error (s.e.) 0·06), P = 0·044) and (ß = -0·1057 (s.e. = 0·05), P = 0·033), respectively. There was no statistically significant association among males. Our findings suggest that prevention or treatment of persistent pathogens, in particular CMV, may play an important role in reducing telomere shortening over the life course among women. Future research is needed to confirm these novel findings in larger longitudinal samples.

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics.

In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.

Reduced susceptibilities to biocides and resistance to antibiotics in food-associated bacteria following exposure to quaternary ammonium compounds.

AIMS: Our aim was to assess the effects of step-wise exposure to didecyl dimethyl ammonium chloride (DDAC) on the antimicrobial (antibiotics and biocides) susceptibilities of food-associated bacterial strains. METHODS AND RESULTS: Adaptive responses of bacterial strains were investigated by exposing the strains daily to increasing subinhibitory concentrations of DDAC for 7 days. Following adaptation to DDAC, a threefold increase in the minimum inhibitory concentration (MIC) values for this biocide was observed in 48% of the Escherichia coli and Listeria monocytogenes strains, and 3% of the Salmonella strains. Reduced susceptibility to other biocides was found with the most important increase in MIC for benzalkonium chloride (BC) and a commercial biocide formulation (Galox Horizon) containing DDAC and glutaraldehyde, for all species except Salmonella. Increase in antibiotic MIC values was more pronounced in E. coli in terms of antibiotic numbers and of magnitude (from 4- to 32-fold increase) and, to a lesser extent, in Salmonella strains. Most of these strains had acquired resistance to ampicillin, cefotaxime, ceftazidime, chloramphenicol and ciprofloxacin. CONCLUSIONS: The effects of exposure to DDAC on biocides and antibiotics susceptibilities depend upon the bacteria species. SIGNIFICANCE AND IMPACT OF THE STUDY: Extensive use of DDAC at subinhibitory concentrations may lead to the development of antibiotic-resistant bacteria and may represent a public health issue.

Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes.

BACKGROUND: We reviewed our experience with tracheal extubation in the operating room (E-OR) among cystic fibrosis patients requiring bilateral lung transplantation to evaluate safety and determine predictive factors of E-OR. METHODS: The charts of 89 recipients (from May 2007 to June 2013) were analysed. Patients were divided into E-OR and E-ICU (intensive care unit extubation) groups. Data are expressed as numbers (percentages) or medians [25th-75th percentiles]. RESULTS: There were 41 patients in the E-OR group (46%). Donor and recipient characteristics were similar between groups. Intraoperative complications occurred less frequently in the E-OR group, and fluid and transfusion requirements were lower. Postoperative courses were different in the E-OR group, including a lower rate of grade 3 primary graft dysfunction (0 compared with 19 patients, P<0.0001) and shorter ICU (5.0 [3.7-7.2] compared with 11.5 [7.0-15.5] days) and hospital stays (22.0 [18.0-25.5] compared with 33.0 [25.0-56.5] days, respectively; P<0.0001 for both). The 1 yr survival rates were similar: 95% in the E-OR group and 98% in the E-ICU group. A statistical model built on a development cohort of 60 randomly selected patients predicted 95% of E-OR instances in this cohort and 82% of E-OR instances in the validation cohort (28 patients). Predictive factors were complications during single-lung ventilation (second graft implantation), complications during bipulmonary ventilation (end of surgery), and the ratio of arterial partial pressure of oxygen to fractional inspired oxygen (end of surgery). CONCLUSIONS: Our protocol allowed for extubation of 46% of bilateral lung transplant patients without increased postoperative risks.

Blood stream infections due to multidrug-resistant organisms among spinal cord-injured patients, epidemiology over 16 years and associated risks: a comparative study.

STUDY DESIGN: Retrospective study. OBJECTIVES: We aimed to describe the epidemiology of multidrug-resistant organisms (MDROs) during bloodstream infection (BSI) and identify associated risks of MDROs among patients with spinal cord injury (SCI). SETTING: A teaching hospital, expert center in disability, in France. METHODS: We studied a retrospective cohort of all BSIs occurring in SCI patients hospitalized over 16 years. We described the prevalence of MDRO BSI among this population and its evolution over time and compared the BSI population due to MDROs and due to non-MDROs. RESULTS: A total of 318 BSIs occurring among 256 patients were included in the analysis. The most frequent primary sites of infection were urinary tract infection (34.0%), pressure sore (25.2%) and catheter line-associated bloodstream infection (11.3%). MDROs were responsible for 41.8% of BSIs, and this prevalence was stable over 16 years. No significant associated factor for MDRO BSI could be identified concerning sociodemographic and clinical characteristics, primary site of infection and bacterial species in univariate and multivariate analyses. BSI involving MDROs was not associated with initial severity of sepsis compared with infection without MDROs (43.8 vs 43.6%, respectively) and was not associated either with 30th-day mortality (6.2 vs 9%, respectively). CONCLUSION: During BSI occurrence in an SCI population, MDROs are frequent but remain stable over years. No associated risk can be identified that would help optimize antibiotic treatment. Neither the severity of the episode nor the mortality is significantly different when an MDRO is involved.

Rifle impulse noise affects middle-ear compliance in soldiers wearing protective earplugs.

OBJECTIVE: We tested middle-ear functioning in humans following intense exposure to noise. Noise generated by small caliber firearms was thought to have no effect on the middle-ear. DESIGN: A cross-over design. We measured middle-ear impedance, acoustic reflex, distortion product otoacoustic emissions (DPOAEs), and transient evoked otoacoustic emissions (TEOAEs) before and after practice rounds performed twice per day. STUDY SAMPLE: Fifty-nine soldiers equipped with earplugs undergoing regular training for a special mission. The mean noise exposure (LAeq8h) was estimated to be 106 ±1 dB SPL. RESULTS: Impedancemetry revealed a significant increase in the compliance and gradient of the tympano-ossicular chain after impulse noise exposure in the right and left ears. Acoustic reflex reactivity did not show a significant change. DPOAEs and TEOAEs were slightly decreased at 2 kHz, and showed a marked asymmetry in disfavor of the left ear. In soldiers with initial high reactivity of acoustic reflex, increased compliance was associated with a significant decrease in left TEOAEs at 1.5 and 2 kHz. CONCLUSION: Our results suggest that the use of small-caliber firearms, even while wearing earplugs, affects middle-ear function and may play a role in the early stage of auditory fatigue encompassing tinnitus.

[Management of Adult Community-acquired Pneumonia and Prevention - Update 2016]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie und Prävention - Update 2016.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

BDNF-TrkB signaling through Erk1/2 MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids.

Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.

Canal wall reconstruction in cholesteatoma surgeries: rate of residual.

To evaluate the rates of residual and recurrent cholesteatoma following canal wall reconstruction (CWR) tympano-mastoidectomy with mastoid obliteration, for the treatment of chronic otitis with cholesteatoma. Consecutive cohort study. We included patients following surgical cholesteatoma removal by CWR tympano-mastoidectomy with hydroxyapatite mastoid obliteration from 2008 to 2012. We analyzed audiometric and postoperative radiologic data. We determined the rates of residual disease and recurrence, and evaluated postoperative complications. Thirty-six ears were included in this study. The mean follow-up after surgery was 24 months (range 12.3-51.4 months). The recurrence rate was 3.1% (one case) and the rate of residual disease was 6.2% (two cases including one of iatrogenic cholesteatoma). No canal-wall-down tympanoplasty was required. Local infection was detected in 33% of cases and was successfully treated with appropriate antibiotics. Postoperative audiometry showed no impairment of the cochlear reserve. No postoperative facial palsy or deafness was observed. CWR permits well exposure of the lesion, making complete excision of the cholesteatoma possible. This study showed a decreasing of the rate of residual cholesteatoma and must be confirmed with further studies. CWR makes it possible to use hearing aids for auditory rehabilitation.