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Jonas Alexander Leppig,1 Lan Song,2 Dorothea C Voigt,1 Felix W Feldhaus,1 Christoph Ruwwe-Gloesenkamp,3 Jacopo Saccomanno,3 Bianca C Lassen-Schmidt,4 Konrad Neumann,5 Katja Leitner,6 Ralf H Hubner,3 Felix Doellinger1 1Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany; 2Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; 4Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany; 5Institute of Biometrics and Clinical Epidemiology, Charité Universitätsmedizin Berlin, Berlin, Germany; 6Department of Internal Medicine, Kantonsspital Aarau AG, Aarau, SwitzerlandCorrespondence: Jonas Alexander Leppig, Department of Radiology, Charité Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin, 13353, Germany, Tel + 49 30 450 627 283, Fax + 49 30 450 527 911, Email Jonas-Alexander.Leppig@charite.dePurpose: To investigate changes in quantitative CT analysis (QCT) and pulmonary function tests (PFT) in pulmonary emphysema patients who required premature removal of endobronchial valves (EBV).Patients and Methods: Our hospital’s medical records listed 274 patients with high-grade COPD (GOLD stages 3 and 4) and pulmonary emphysema who were treated with EBV to reduce lung volume. Prior to intervention, a complete evaluation was performed that included quantitative computed tomography analysis (QCT) of scans acquired at full inspiration and full expiration, pulmonary function tests (PFT), and paraclinical findings (6-minute walking distance test (6MWDT) and quality of life questionnaires). In 41 of these 274 patients, EBV treatment was unsuccessful and the valves had to be removed for various reasons. A total of 10 of these 41 patients ventured a second attempt at EBV therapy and underwent complete reevaluation. In our retrospective study, results from three time points were compared: Before EBV implantation (BL), after EBV implantation (TP2), and after EBV explantation (TP3). QCT parameters included lung volume, total emphysema score (TES, ie, the emphysema index) and the 15th percentile of lung attenuation (P15) for the whole lung and each lobe separately. Differences in these parameters between inspiration and expiration were calculated (Vol. Diff (%), TES Diff (%), P15 Diff (%)). The results of PFT and further clinical tests were taken from the patient’s records.Results: We found persistent therapy effect in the target lobe even after valve explantation together with a compensatory hyperinflation of the rest of the lung. As a result of these two divergent effects, the volume of the total lung remained rather constant. Furthermore, there was a slight deterioration of the emphysema score for the whole lung, whereas the TES of the target lobe persistently improved.Conclusion: Interestingly, we found evidence that, contrary to our expectations, unsuccessful EBV therapy can have a persistent positive effect on target lobe QCT scores.Keywords: chronic obstructive pulmonary disease, pulmonary emphysema, endobronchial valves, lung volume reduction, computed tomography, pulmonary function test

Felix W Feldhaus,1 Dorothea Cornelia Theilig,1 Ralf-Harto Hubner,2 Jan-Martin Kuhnigk,3 Konrad Neumann,4 Felix Doellinger11Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Department of Radiology, Berlin, Germany; 2Department of Internal Medicine/Infectious and Respiratory Disease, Charité Universitätsmedizin Berlin, Berlin, Germany; 3Institute for Medical Image Computing, Fraunhofer MEVIS, Bremen, Germany; 4Institute of Biometrics and Clinical Epidemiology, Charité Universitätsmedizin Berlin, Berlin, GemanyPurpose: Quantitative analysis of CT scans has proven to be a reproducible technique, which might help to understand the pathophysiology of chronic obstructive pulmonary disease (COPD) and combined pulmonary fibrosis and emphysema. The aim of this retrospective study was to find out if the lung function of patients with COPD with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV and pulmonary emphysema is measurably influenced by high attenuation areas as a correlate of concomitant unspecific fibrotic changes of lung parenchyma.Patients and methods: Eighty-eight patients with COPD GOLD stage III or IV underwent CT and pulmonary function tests. Quantitative CT analysis was performed to determine low attenuation volume (LAV) and high attenuation volume (HAV), which are considered to be equivalents of fibrotic (HAV) and emphysematous (LAV) changes of lung parenchyma. Both parameters were determined for the whole lung, as well as peripheral and central lung areas only. Multivariate regression analysis was used to correlate HAV with different parameters of lung function.Results: Unlike LAV, HAV did not show significant correlation with parameters of lung function. Even in patients with a relatively high HAV of more than 10%, in contrast to HAV (p=0.786) only LAV showed a significantly negative correlation with forced expiratory volume in 1 second (r=−0.309, R2=0.096, p=0.003). A severe decrease of DLCO% was associated with both larger HAV (p=0.045) and larger LAV (p=0.001). Residual volume and FVC were not influenced by LAV or HAV.Conclusion: In patients with COPD GOLD stage III-IV, emphysematous changes of lung parenchyma seem to have such a strong influence on lung function, which is a possible effect of concomitant unspecific fibrosis is overwhelmed.Keywords: COPD, quantitative CT, pulmonary fibrosis, pulmonary emphysema, CPFE

Dorothea Theilig,1 Felix Doellinger,1 Alexander Poellinger,1 Vera Schreiter,1 Konrad Neumann,2 Ralf-Harto Hubner31Department of Radiology, Charité Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Berlin, Germany; 2Institute of Biometrics and Clinical Epidemiology, Charité Campus Benjamin Franklin, Charité, Universitätsmedizin Berlin, Berlin, Germany; 3Department of Pneumology, Charité Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Berlin, GermanyBackground: The degree of interlobar emphysema heterogeneity is thought to play an important role in the outcome of endoscopic lung volume reduction (ELVR) therapy of patients with advanced COPD. There are multiple ways one could possibly define interlobar emphysema heterogeneity, and there is no standardized definition.Purpose: The aim of this study was to derive a formula for calculating an interlobar emphysema heterogeneity index (HI) when evaluating a patient for ELVR. Furthermore, an attempt was made to identify a threshold for relevant interlobar emphysema heterogeneity with regard to ELVR.Patients and methods: We retrospectively analyzed 50 patients who had undergone technically successful ELVR with placement of one-way valves at our institution and had received lung function tests and computed tomography scans before and after treatment. Predictive accuracy of the different methods for HI calculation was assessed with receiver-operating characteristic curve analysis, assuming a minimum difference in forced expiratory volume in 1 second of 100 mL to indicate a clinically important change.Results: The HI defined as emphysema score of the targeted lobe (TL) minus emphysema score of the ipsilateral nontargeted lobe disregarding the middle lobe yielded the best predicative accuracy (AUC =0.73, P=0.008). The HI defined as emphysema score of the TL minus emphysema score of the lung without the TL showed a similarly good predictive accuracy (AUC =0.72, P=0.009). Subgroup analysis suggests that the impact of interlobar emphysema heterogeneity is of greater importance in patients with upper lobe predominant emphysema than in patients with lower lobe predominant emphysema.Conclusion: This study reveals the most appropriate ways of calculating an interlobar emphysema heterogeneity with regard to ELVR. Keywords: CT-quantitative, COPD, emphysema heterogeneity, endoscopic lung volume reduction

Christian Thomsen,1 Dorothea Theilig,2 Dominik Herzog,1 Alexander Poellinger,2 Felix Doellinger,2 Nils Schreiter,3 Vera Schreiter,2 Dirk Schürmann,1 Bettina Temmesfeld-Wollbrueck,1 Stefan Hippenstiel,1 Norbert Suttorp,1 Ralf-Harto Hubner1 1Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, 2Institute of Radiology, 3Institute of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany Abstract: The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. Keywords: endoscopic lung volume reduction, COPD, valves, lung perfusion, emphysema distribution

Dirk Schürmann, Jacopo Saccomanno, Bettina Temmesfeld-Wollbrück, Martin Witzenrath, Ralf-Harto Hübner Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, 10117, GermanyCorrespondence: Dirk Schürmann, Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité - Universitätsmedizin Berlin, Berlin, 10117, Germany, Tel +49 30 450 653318 ; +49 1723871964, Email dirk.schuermann@charite.deAbstract: The risk of foreign body aspiration associated with uncapped handheld metered-dose inhalers (MDIs) is underestimated. We report a case in which a plastic cable clip accidentally lodged in the mouthpiece of an uncapped pressurized MDI was aspirated during its use. A literature search revealed 16 other cases of foreign body aspiration associated with uncapped handheld inhalers, all but one of which were pressurized inhalers. Patients should be informed of the risk of foreign body aspiration associated with uncapped pocket inhalers. The use of an uncuffed armoured tracheal tube with a separate oxygen tubing during flexible bronchoscopy for foreign body removal ensures a safe airway. Foreign bodies that exceed the lumen size of the tracheal tube can be pulled to the distal opening with forceps and removed when the tube is withdrawn.Plain Language Summary: Handheld pocket inhalers have significantly improved the treatment of patients with chronic obstructive pulmonary disease. We report a case in which a plastic cable clip accidentally lodged in the mouthpiece of an uncapped pressurized pocket inhaler was aspirated during its use. Depressing the plunger of the inhaler released the inhalant in a high-velocity spray, which was inhaled with a deep breath while simultaneously aspirating the plastic cable clip. The risk of foreign body aspiration associated with uncapped pressurized metered-dose inhalers is underestimated. Patients using pocket inhalers should be informed of the risk of foreign body aspiration with uncapped inhalers. Inhalers should always be kept capped except during use to prevent small objects from accidentally entering the mouthpiece. The cap of the inhaler mouthpiece should only be removed when the inhaler is used. Foreign bodies that have accidentally become lodged in the mouthpiece of an inhaler and aspirated into the lungs can usually be removed by specialists during a short outpatient procedure.Keywords: foreign body aspiration, metered-dose inhaler, removal of aspirated foreign bodies, uncuffed armoured tracheal tube with separate oxygen tubing

Arschang Valipour,1 Pallav L Shah,2 Felix J Herth,3 Christophe Pison,4 Christian Schumann,5 Ralf-Harto Hübner,6 Peter I Bonta,7 Romain Kessler,8 Wolfgang Gesierich,9 Kaid Darwiche,10 Bernd Lamprecht,11 Thierry Perez,12 Dirk Skowasch,13 Gaetan Deslee,14 Armelle Marceau,15 Frank C Sciurba,16 Reinoud Gosens,17 Jorine E Hartman,18 Francesca Conway,2 Marina Duller,1 Martin Mayse,19 Holly S Norman,19 Dirk-Jan Slebos18 On behalf of the AIRFLOW-2 Trial Study Group1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik Floridsdorf, Vienna, Austria; 2Royal Brompton & Harefield NHS Trust, Chelsea & Westminster Hospital and Imperial College, London, UK; 3Thoraxklinik, Department of Pneumology and Critical Care Medicine and Translational Lung Research Center Heidelberg (TLRCH), University of Heidelberg, Heidelberg, Germany; 4CHU Grenoble Alpes, Service Hospitalier Universitaire Pneumologie Physiologie; Université Grenoble Alpes, Grenoble, France; 5Clinic of Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care, Klinikverbund Allgaeu, Kempten and Immenstadt, Germany; 6Charité Universitätsmedizin Berlin, Medizinische Klinik m. Schw. Infektiologie und Pneumologie, Campus Virchow, Berlin, Germany; 7Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 8Service de Pneumologie, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France; 9Asklepios-Fachkliniken Munich-Gauting, Comprehensive Pneumology Center Munich, Gauting, Germany; 10Department of Pulmonary Medicine, Section of Interventional Pneumology, Ruhrlandklinik - University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 11Department of Pulmonary Medicine, Kepler Universitatsklinikum GmbH, Linz, Austria; 12CHU de Lille – Hôpital Calmette, Lille, France; 13Department of Internal Medicine II - Cardiology/Pneumology, University of Bonn, Bonn, Germany; 14CHU de Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France; 15Service de Pneumologie, Hôpital Universitaire Bichat, Paris, France; 16University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 17Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; 18Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 19Nuvaira, Inc., Minneapolis, MN, USACorrespondence: Dirk-Jan SlebosDepartment of Pulmonary Diseases/Interventional Bronchoscopy AA11, University Medical Center Groningen, PO Box 30001, Groningen, the NetherlandsTel +31 503612357Fax +31503619320Email d.j.slebos@umcg.nlPurpose: COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization.Patients and Methods: TLD was performed in COPD patients (FEV1 30– 60% predicted, CAT≥ 10 or mMRC≥ 2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed.Results: Eighty-two subjects (FEV1 41.6± 7.4% predicted, 50.0% male, age 63.7± 6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups.Conclusion: In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD.Clinical Trial Registration: NCT02058459.Keywords: COPD exacerbation, targeted lung denervation, bronchoscopy, COPD

Karin Klooster,1,* T David Koster,1,* Christoph Ruwwe-Glösenkamp,2 Dorothea Theilig,3 Felix Doellinger,3 Jacopo Saccomanno,2 Huib AM Kerstjens,1 Dirk-Jan Slebos,1 Ralf-Harto Hübner2 1University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands; 2Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Pneumology, Berlin, Germany; 3Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Radiology, Berlin, Germany*These authors contributed equally to this workCorrespondence: Karin Klooster Email k.klooster@umcg.nlPurpose: Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection.Patients and Methods: Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation.Results: An FCS > 95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤ 80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤ 90%, but 69.7% for the right upper lobe fissure.Conclusion: Quantitative CT analysis is recommended in all patients evaluated for endobronchial valves. Patients with incomplete fissures (left major fissure: FCS < 80%; right major fissure: < 90%) can be excluded from Chartis measurement and endobronchial valve treatment. In patients with more complete fissures, the FCS is not specific enough for endobronchial valve treatment decisions. In this case, additional Chartis measurements are always recommended in the right lung. For the left lung, Chartis assessments may be omitted if the FCS is > 95%.Keywords: COPD, lung volume reduction, fissure, collateral ventilation, CT scan

Purpose: The aim of this retrospective study was to evaluate correlations between parameters of quantitative computed tomography (QCT) analysis, especially the 15th percentile of lung attenuation (P15), and parameters of clinical tests in a large group of patients with pulmonary emphysema., Patients and Methods: One hundred and seventy-two patients with pulmonary emphysema and chronic obstructive pulmonary disease (COPD) global initiative for chronic obstructive lung disease (GOLD) stage 3 or 4 were assessed by nonenhanced thin-section CT scans in full inspiratory and expiratory breath-hold, pulmonary function test (PFT), a 6-minute walk test (6MWT), and quality of life questionnaires (SGRQ and CAT). QCT parameters included total lung volume (TLV), total emphysema score (TES), and P15, all measured at inspiration (IN) and expiration (EX). Differences between inspiration and expiration were calculated for TLV (TLV Diff ), TES (TES Diff ), and P15 (P15 Diff ). Spearman correlation analysis was performed., Results: CT-measured lung volume in inspiration (TLV IN ) correlated strongly with spirometry-measured total lung capacity (TLC) (r=0.81, p <0.001) and moderately to strongly with residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV 1 )/FVC (r=0.60, 0.56, and -0.49, each p <0.001). Lung volume in expiration (TLV EX ) correlated moderately to strongly with TLC, RV and FEV 1 /FVC ratio (r=0.75, 0.66, and -0.43, each p <0.001). TES and P15 showed stronger correlations with the carbon monoxide transfer coefficient (KCO%) (r= -0.42, 0.44, both p <0.001), when measured during expiration. P15 Diff correlated moderately with KCO% and carbon monoxide diffusing capacity (DLCO%) (r= 0.41, 0.40, both p <0.001). The 6MWT and most QCT parameters showed significant differences between COPD GOLD 3 and 4 groups., Conclusion: Our results suggest that QCT can help predict the severity of lung function decrease in patients with pulmonary emphysema and COPD GOLD 3 or 4. Some QCT parameters, including P15 EX and P15 Diff , correlated moderately to strongly with parameters of pulmonary function tests., Competing Interests: Author Bianca C Lassen-Schmidt is an employee of Fraunhofer MEVIS, the developer of the MeVis PULMO3D software. Ralf H Hubner reports personal fees from Pulmonx during the conduct of the study. All other authors report no conflicts of interest in this work., (© 2020 Song et al.)

The treatment of symptomatic lung emphysema by lung volume reduction has become established over the last 15 years. While surgical partial lung resection has profited from improved and less invasive surgical techniques, various endoscopic interventional procedures have been developed and are now available for use. All treatment approaches are dependent on individual anatomical variants and a regional distribution of the lung emphysema, which is why no procedure can be designated as the gold standard for all patients. High-resolution computed tomography can be qualitatively evaluated and provides decisive information for treatment, which is why radiologists play a particularly important role in treatment planning and aftercare of an intervention for reduction of the lung volume. This article presents the various endoscopic techniques, names the demands of the treating physician on the advising radiologist and finally describes how a treatment decision is derived from the results obtained.

Rationale: Endobronchial valves (EBVs) have been successfully used in patients with severe heterogeneous emphysema to improve lung physiology. Limited available data suggest that EBVs are also effective in homogeneous emphysema., Objectives: To evaluate the efficacy and safety of EBVs in patients with homogeneous emphysema with absence of collateral ventilation assessed with the Chartis system., Methods: Prospective, multicenter, 1:1 randomized controlled trial of EBV plus standard of care (SoC) or SoC alone. Primary outcome was the percentage change in FEV 1 (liters) at 3 months relative to baseline in the EBV group versus the SoC group. Secondary outcomes included changes in FEV 1 , St. George's Respiratory Questionnaire (SGRQ), 6-minute-walk distance (6MWD), and target lobe volume reduction., Measurements and Main Results: Ninety-three subjects (age, 63.7 ± 6.1 yr [mean ± SD]; FEV 1 , % predicted, 29.3 ± 6.5; residual volume, % predicted, 275.4 ± 59.4) were allocated to either the EBV group (n = 43) or the SoC group (n = 50). In the intention-to-treat population, at 3 months postprocedure, improvement in FEV 1 from baseline was 13.7 ± 28.2% in the EBV group and -3.2 ± 13.0% in the SoC group (mean between-group difference, 17.0%; P = 0.0002). Other variables demonstrated statistically and clinically significant changes from baseline to 3 months (EBV vs. SoC, respectively: SGRQ, -8.63 ± 11.25 vs. 1.01 ± 9.36; and 6MWD, 22.63 ± 66.63 m vs. -17.34 ± 52.8 m). Target lobe volume reduction at 3 months was -1,195 ± 683 ml (P < 0.0001). Of the EBV subjects, 97.2% achieved volume reduction in the target lobe (P < 0.0001). Procedure-related pneumothoraces occurred in 11 subjects (25.6%). Five subjects required removal/replacement of one or more valves. One subject experienced two valve migration events requiring removal/replacement of valves., Conclusions: EBV in patients with homogeneous emphysema without collateral ventilation results in clinically meaningful benefits of improved lung function, exercise tolerance, and quality of life.

Objective: Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax., Methods: Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC))., Results: The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts., Conclusions: In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data.

Congenital hypotrichosis and Stargardt macular dystrophy are rare autosomal recessive disorder of unknown etiology respectively characterized by hair loss, macular degeneration and severe progressive vision reduction. There are few reports in the literature with this association. Studies show that the defective gene is on the chromosome I6q22.1 and involve cadherin molecule in the pathogenesis. Early recognition of these disorders often starts with hair changes and should alert the dermatologist for an eye examination thereby avoiding more severe ocular defect.

Background: Uremic pruritus is the most frequent symptom in long-term hemodialysis patients. Abnormal laboratory parameters have been found with conflicting data., Objective: To correlate the prevalence of pruritus with alterations in mineral metabolism in hemodialysis patients., Methods: This was a case-control study. A hundred and five patients on maintenance hemodialysis were evaluated: a group of patients with pruritus and a control group. They answered a research protocol questionnaire; laboratory data were collected from medical records and the patients with pruritus filled out a visual analogue scale (VAS) to measure pruritus level., Results: The mean age was 51.9 years; 59% of the patients were men and 43% of the patients had pruritus. Xeroderma occurred in 45% of the patients. High levels of calcium were demonstrated in 55% of the patients and 47% had pruritus. 60% of the patients had high phosphorus levels and 43% had pruritus. The Ca/P ratio was normal for all the patients. Parathyroid hormone was high in 95% of the patients, all of them referring pruritus., Conclusion: There was a statistically significant association between the group of patients with pruritus and xeroderma. Serum calcium and phosphorus levels, Ca/P ratio, PTHi and size of the dialyzer did not show a statistically significant association with pruritus. Therefore, we found an important relationship between xeroderma and pruritus, with no relation with the assessed laboratory parameters.

Bone marrow contains distinct microenvironments that regulate hematopoietic stem cells (HSCs). The endosteal HSC niche includes osteoblasts, mineral, and extracellular matrix proteins that interact through various molecular signals to control HSCs. Sonic hedgehog (Shh) is a morphogen involved in the regulation of skeletal development and hematopoiesis, but the effects of Shh on bone in relation to the HSC niche are not well understood. We demonstrate that systemic overexpression of Shh in mice increases osteoblast number with the resultant formation of new trabeculae in the femoral diaphysis. Suggestive of a functional change in the hematopoietic niche, numbers of Lin(-) Sca-1(+) c-Kit(+) cells with hematopoietic progenitor function expand, although cells with in vivo repopulating capacity in the wild-type environment do not increase. Instead, Shh mediates a decrease in number of bone marrow lymphocytes accompanied by a decreased expression of stromal-derived growth factor 1 (SDF-1) and a decrease in Flk2-expressing Lin(-) Sca-1(+) c-Kit(+) cells, indicating a modulation of early lymphopoiesis. This is caused by a microenvironment-induced mechanism as Shh treatment of bone marrow recipients, but not donors, results in a dramatic depletion of lymphocytes. Together, these data suggest that Shh mediates alterations in the bone marrow hematopoietic niche affecting the early lymphoid differentiation.

Autophagy is an intracellular pathway that contributes to the degradation and recycling of unfolded proteins. Based on the knowledge that autophagy affects glycogen metabolism and that alpha(1)-antitrypsin (AAT) deficiency is associated with an autophagic response in the liver, we hypothesized that the conformational abnormalities of the Z-AAT protein interfere with hepatocyte glycogen storage and/or metabolism. Compared with wild-type mice (WT), the Z-AAT mice had lower liver glycogen stores (P < 0.001) and abnormal activities of glycogen-related enzymes, including acid alpha-glucosidase (P < 0.05) and the total glycogen synthase (P < 0.05). As metabolic consequences, PiZ mice demonstrated lower blood glucose levels (P < 0.05), lower body weights (P < 0.001), and lower fat pad weights (P < 0.001) compared with WT. After the stress of fasting or partial hepatectomy, PiZ mice had further reduced liver glycogen and lower blood glucose levels (both P < 0.05 compared WT). Finally, PiZ mice exhibited decreased survival after partial hepatectomy (P < 0.01 compared with WT), but this was normalized with postoperative dextrose supplementation. In conclusion, these observations are consistent with the general concept that abnormal protein conformation and degradation affects other cellular functions, suggesting that diseases in the liver might benefit from metabolic compensation if glycogen metabolism is affected.