Patients With Severe Alcohol-Related Cognitive Impairment Improve in Flexibility When Abstinence Is Maintained: A Comparative Study With Alzheimer's Disease.

The disease progression of severe alcohol-related cognitive impairment (ARCI) is debated. The aim of this study was to compare the cognitive change of patients with severe ARCI in inpatient setting to that of patients with Alzheimer's disease (AD). Fifteen consecutive patients with severe ARCI were recruited between 2013 and 2015. They received inpatient detoxification, neurological assessment, and inpatient cognitive rehabilitation in specialized facilities. Twelve patients, with documented AD matched on sex and initial cognitive impairment severity, were selected. All have benefited from two neuropsychological assessments. The neurocognitive change was tested in both groups with pair-wised Wilcoxon tests. ARCI and AD patients' time course was compared with Mann-Whitney-Wilcoxon test. In ARCI group, first assessment occurred at 2.9 (± 2.2) months of abstinence and follow-up 6.5 (± 2.9) months later, the mean age was 56.5 (± 7.4) years, and 12 were men. In AD group, follow-up occurred at 12.8 (± 2.9) months (p < 10-3), the mean age was 72.3 (± 8.4) years (p < 10-3), and 10 were men. ARCI patients significantly improved on one executive function test (TMT-B; p < 0.05), while AD patients have worsened memory subtests on Free-and-Cued-Selective-Reminding Test (p < 0.05). These tests showed a statistically different change between severe ARCI and AD group (p < 0.05). Severe ARCI patients have improved in executive functioning, discernible on the TMT-B test, in specific care setting, including abstinence maintenance and rehabilitation. The disease progression was different from that observed in AD patients.

Accuracy of endobronchial ultrasound-guided transbronchial needle aspiration in HIV-infected patients with thoracic lymphadenopathy in a tuberculosis low-burden area.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an innovative technique to explore hilar and mediastinal lymphadenopathy. We aimed to assess its diagnostic accuracy in HIV-infected patients in a tuberculosis low-burden area. A retrospective review was performed of all HIV-infected patients with thoracic lymphadenopathy referred for EBUS-TBNA between January 2012 and January 2019 in 3 Northern French Hospitals. A total of 15 patients was included during the study period. Our patients were predominantly male (80%), with a mean age of 50 ± 11 years. Six patients (43%) had a CD4 cells count of less than 200/mm3. Eleven patients (73%) were receiving antiretroviral therapy, and 7 (47%) reached undetectable viral load. Adequate lymphnode sampling was accomplished in all patients. No serious complications were reported. EBUS-TBNA led to a definitive diagnosis in 12 out of 15 patients (80%). It identified 4 neoplasia, 3 atypical mycobacterial diseases, 2 tuberculosis, 1 Castleman disease, 1 sarcoidosis, and 1 professional dustiness. In 3 cases, sampling revealed normal lymphoid tissue. Active surveillance confirmed the suspected diagnosis of HIV adenitis with regression of lymphadenopathy on antiretroviral therapy in 2 cases. In one case of negative sampling, thoracoscopy led to the diagnosis of tuberculosis. In our cohort, accuracy of EBUS-TBNA was 92%. EBUS-TBNA appeared to be a safe and accurate tool in the investigation of mediastinal lymphadenopathy in HIV-infected patients in settings of tuberculosis low-prevalence. It can avoid more invasive procedures such as mediastinoscopy.

Dupuytren's disease: personal factors and occupational exposure.

BACKGROUND: The etiology of Dupuytren's disease is unknown, and the role of occupational exposure is still debated. Our objective was to study the association between occupational exposures, personal risk factors and Dupuytren's disease. METHODS: In this cross-sectional survey, nine occupational physicians performed clinical examinations, focused on Dupuytren's disease, of 2,406 French male civil servants employed at the Equipment Ministry in 1998 and interviewed them about medical history, leisure manual exposure and occupational biomechanical exposure to vibrations and manual work. A cumulative occupational exposure score was defined, with three levels of exposure. RESULTS: Dupuytren's disease was diagnosed in 212 men (8.8%). The occupational exposure score was significantly higher in this group of cases than in the rest of the sample (377 (SD280) vs. 223 (SD250), respectively; P < 0.0001). Occupational exposure was associated with Dupuytren's disease (adjusted Odds Ratio = 2.20 [1.39-3.45] for the intermediate and 3.10 [1.99-4.84] for the high exposure groups), with adjustment for age, leisure physical activities, alcohol consumption (> or =5 servings per day), history of diabetes, epilepsy, hand trauma, and familial history of Dupuytren's disease. CONCLUSION: Manual work exposure was associated with Dupuytren's disease after adjustment for personal risk factors. Longitudinal studies are needed to confirm these results.

Impact of bronchial epithelium on dendritic cell migration and function: modulation by the bacterial motif KpOmpA.

Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c(+) and I-A(d+) myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.

Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment.

BACKGROUND: Airway dendritic cells (DCs) are crucial for allergen-induced sensitization and inflammation in allergic asthma. After allergen challenge, an increased number of DCs is observed in airway epithelium from patients with allergy. OBJECTIVE: Because Der p 1, a cysteine protease allergen from Dermatophagoides pteronyssinus , induces chemokine production by bronchial epithelial cells (BECs), the purpose of this investigation was to evaluate the capacity of BEC exposed to Der p 1 to recruit DCs. METHODS: Chemotactic activity of BEAS-2B, a bronchial epithelial cell line, and BECs from nonatopic controls and patients with allergic asthma was evaluated on the migration of precursors, immature and mature monocyte-derived DCs (MDDCs), and CD34 + -derived Langerhans cells (LCs). RESULTS: C-C chemokine ligand (CCL)-2, CCL5, and C-X-C chemokine ligand 10 production by BEAS-2B and BEC was increased after Der p 1 exposure, whereas the proenzyme proDer p 1 devoid of enzymatic activity had no effect. Der p 1 stimulation of BEAS-2B and BEC from both groups increased significantly the recruitment of MDDC precursors, depending on CCL2, CCL5, and C-X-C chemokine ligand 10 production. In a reconstituted polarized epithelium, apical application of Der p 1 enhanced MDDC precursor migration into the epithelial layer. Moreover, Der p 1 stimulation of BEC from patients with asthma but not from controls increased the migration of LC precursors, mainly dependent on CCL20 secretion. No migration of immature and mature DCs was observed. CONCLUSION: These data confirmed that BECs participate in the homeostasis of the DC network present within the bronchial epithelium through the secretion of chemokines. In allergic asthma, upregulation of CCL20 production induced LC recruitment, the role of which remains to be determined.

Outer membrane protein A from Klebsiella pneumoniae activates bronchial epithelial cells: implication in neutrophil recruitment.

Aside from its mechanical barrier function, bronchial epithelium plays an important role both in the host defense and in the pathogenesis of inflammatory airway disorders. To investigate its role in lung defense, the effect of a bacterial cell wall protein, the outer membrane protein A from Klebsiella pneumoniae (kpOmpA) on bronchial epithelial cells (BEC) was evaluated on adhesion molecule expression and cytokine production. Moreover, the potential implication of this mechanism in kpOmpA-induced lung inflammation was also determined. Our in vitro studies demonstrated that kpOmpA strongly bound to BEAS-2B cells, a human BEC line, and to BEC primary cultures, resulting in NF-kappaB signaling pathway activation. Exposure to kpOmpA increased ICAM-1 mRNA and cell surface expression, as well as the secretion of IL-6, CXC chemokine ligand (CXCL)1, CXCL8, C-C chemokine ligand 2, CXCL10 by BEAS-2B cells, and BEC primary cultures (p < 0.005). We analyzed in vivo the consequences of intratracheal injection of kpOmpA to BALB/c mice. In kpOmpA-treated mice, a transient neutrophilia (with a maximum at 24 h) was observed in bronchoalveolar lavage and lung sections. In vivo kpOmpA priming induced bronchial epithelium activation as evaluated by ICAM-1 and CXCL1 expression, associated with the secretion of CXCL1 and CXCL5 in bronchoalveolar lavage fluids. In the lung, an increased level of the IL-6, CXCL1, CXCL5, CXCL10 mRNA was observed with a maximum at 6 h. These data showed that kpOmpA is involved in host defense mechanism by its ability to activate not only APC but also BEC, resulting in a lung neutrophilia.

Chronic interstitial pneumonia with honeycombing in coal workers.

BACKGROUND: Coal worker's pneumoconiosis (CWP) results from coal mine dust inhalation. PATIENTS AND METHODS: We report here the presence of a chronic interstitial pneumonia (CIP) with honeycombing in 38 cases of coal miners, with or without CWP. The 38 patients were selected on the basis of clinical criteria which are unusual in CWP, i.e. fine inspiratory crackles and severe dyspnea. There were 37 men and one woman; mean age was 67.5 +/- 9.1 years. Thirty-two were smokers. Duration of exposure was 26.7 +/- 9.9 years. All the patients had clinical examination, chest radiography, computed tomography (CT), lung function, laboratory investigations, wedged fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). In eight cases, lung specimens were obtained (lung biopsy n = 6, explanted lungs n = 2). RESULTS: Seventeen out of 38 had finger clubbing. 17 had radiological signs of CWP limited to the upper lobes (n = 11) or diffusely distributed (n = 6). CT showed honeycombing (36 cases), and/or ground glass opacities (30 cases) with traction bronchiectasis (8 cases) predominant in the lower lobes. BAL analysis demonstrated an increased percentage of neutrophils (9.4% +/- 6). Lung function showed a restrictive pattern (TLC = 75.1% +/- 16 and FVC = 79.7% +/- 17 of predicted values) associated with a decreased DLCO (50.4 % +/- 22.9 of predicted values) and hypoxemia (at rest = 65.9 mmHg +/- 13.5, upon effort = 56.5 mmHg +/- 13.4). Lung specimens demonstrated in 2 cases a homogenous interstitial fibrosis of intra-alveolar septum with an accumulation of immune and inflammatory cells without temporal variation and with obvious honeycombing. The 6 other cases showed features of usual interstitial pneumonia. CONCLUSION: In presenting these cases, we would like to alert other clinicians to a possible association between CIP with honeycombing and coal dust exposure, with or without associated CWP.