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Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Research Questions: Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients., Study Design and Methods: We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response., Results: 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005)., Conclusion: Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2023.)

Background: The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) for people with cystic fibrosis (pwCF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for pwCF carrying one of 177 rare variants., Methods: An observational study was conducted to evaluate the effectiveness of ETI in pwCF with advanced lung disease that were not eligible to ETI in Europe. All patients with no F508del variant and advanced lung disease (defined as having a percent predicted forced expiratory volume (ppFEV 1 )<40 and/or being under evaluation for lung transplantation) and enrolled in the French Compassionate Program initiated ETI at recommended doses. Effectiveness was evaluated by a centralized adjudication committee at 4-6 weeks in terms of clinical manifestations, sweat chloride concentration and ppFEV 1 ., Results: Among the first 84 pwCF included in the program, ETI was effective in 45 (54%) and 39 (46%) were considered to be non-responders. Among the responders 22/45 (49%) carried a CFTR variant that is not currently approved by FDA for ETI eligibility. Important clinical benefits, including suspending the indication for lung transplantation, a significant decrease in sweat chloride concentration by a median [IQR] -30 [-14;-43]mmol·l -1 (n=42; p <0.0001) and an improvement in ppFEV 1 by+10.0 [6.0; 20.5] (n=44, p <0.0001), were observed in those for whom treatment was effective., Conclusion: Clinical benefits were observed in a large subset of pwCF with advanced lung disease and CFTR variants not currently approved for ETI., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Rationale and Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have revolutionised the treatment of cystic fibrosis (CF). Chest computed tomography (CT) is key in the diagnosis and follow-up of anatomical damage to the lungs. Our study aimed to evaluate changes on lung CT scans of patients with CF after receiving elexacaftor-tezacaftor-ivacaftor (ETI) therapy for one year., Materials and Methods: We conducted a retrospective, observational, single-centre study between 2018 and 2021 on adult patients with CF administered ETI. We reviewed chest CT scans before and at least one year after starting ETI. The Brody-II score (BSII) was measured by two experienced radiologists who were blinded to the treatment. Paranasal sinus CT scans and clinical and functional data were also compared. Wilcoxon tests were used to compare differences, and Spearman's correlation coefficient was used to evaluate changes in forced expiratory volume in one second (FEV 1 ) and total BSII., Results: In the period, 63 patients were given ETI, and 12 met the criteria for analysis. The inter-observer reproducibility of BSII was satisfactory (intraclass correlation coefficient = 0.83, 95% confidence interval 0.57-0.91). The BSII decreased after one year of treatment (-18 ± 16, p = 0.002) due to lower mucous plugging (-7 ± 4, p < 0.001) and peribronchial thickening (-9 ± 10, p = 0.002) scores. Bronchial, parenchymal, and hyperinflation scores were unchanged. Clinical and functional parameters were significantly improved, except for total lung capacity. The correlation between ΔFEV 1 and Δtotal BSII was strong (r = 0.88, p < 0.001). The paranasal sinus CT score significantly improved with ETI treatment., Conclusions: ETI decreased pulmonary and sinus morphological abnormalities after one year of treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Chronic Lung Allograft Dysfunction (CLAD) is the main cause of morbidity and mortality after the first year following lung transplantation (LTx). Risk factors of CLAD have been extensively studied, but the association between gram-negative bacteria (GNB) bronchial colonization and the development of CLAD is controversial. The purpose of our study was to investigate the association between post-transplant recolonization with the same species or de-novo colonization with a new GNB species and CLAD. The same analysis was performed on a sub-group of patients at the strain level using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry technique., Results: Forty adult cystic fibrosis (CF) patients who underwent a first bilateral LTx in the University Hospital of Marseille, between January 2010 and December 2014, were included in the study. Patients with GNB de-novo colonization had a higher risk of developing CLAD (OR = 6.72, p = 0.04) and a lower rate of CLAD-free survival (p = 0.005) compared to patients with GNB recolonization. No conclusion could be drawn from the subgroup MALDI-TOF MS analysis at the strain level., Conclusion: Post-LTx GNB airway recolonization seems to be a protective factor against CLAD, whereas de-novo colonization with a new species of GNB seems to be a risk factor for CLAD.

Purpose of the Study: Vibrating-mesh nebulizers are widely used at home for cystic fibrosis (CF) treatment, with a therapeutic efficiency closely linked to the mesh performance. This national study looks at the maintenance at home by CF patients and their families of the mesh of the eFlow ® rapid nebulizer. Ninety-two patients from 34 French CF centers, treated at home with inhaled drugs delivered with a vibrating-mesh nebulizer, answered to a phone standardized questionnaire specifying the different techniques of maintenance of the nebulizer., Principal Results: Patients were aged from 2 to 68 years (58.7% of children). They inhaled a mean of 1.8 nebulizations per day. Maintenance was assumed by patients in 36% of the cases. All steps of the theoretical maintenance of a nebulizer were respected in 66% of the cases. The mesh was not cleaned in 45.6%, not disinfected or not thermically disinfected in 32.5%, and not rinsed after chemical disinfection in 45.5% of the case. Only 49% of the patients knew the role of the MeshCare ® system in the mesh maintenance, and only 39% had already used it when the nebulization duration reached 10 min., Conclusions: Efforts about education, particularly for the maintenance of the mesh, are needed for CF patients using a vibrating-mesh nebulizer at home., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Primary ciliary dyskinesia (PCD) is a genetic disease characterised by abnormalities in ciliary function, responsible for chronic pulmonary and sinonasal diseases. Adult clinical features and outcome are poorly described., Objectives: To assess the clinical characteristics and disease progression in adults with PCD., Methods: Bicentric retrospective study, focusing on adults (≥18 years) with an asserted diagnosis of PCD based on the presence of bronchiectasis with typical ultrastructural defect of cilia and/or situs inversus (SI). Clinical symptoms, respiratory function, extent of bronchiectasis, microbiology and molecular analysis were assessed. Results are expressed as median (25th; 75th centile)., Results: 78 patients were included with a median follow-up of 8.1 years. 91% of patients had respiratory symptoms and 95% had chronic rhinosinusitis. Half of ultrastructural defects concerned dynein arms. Respiratory function was significantly lower in women (FEV 1 =60% predicted (50; 76), vs 77% (62; 95), p=0.009) and in patients with chronic airway Pseudomonas aeruginosa (PA, n=21) infection (FEV 1 =60% (48; 71) vs 75% (55; 89), p=0.04). FEV 1 was associated with gender (regression coefficient for men =13.8, p=0.009), chest CT score (r=-0.42, p<0.001) but not with age at diagnosis, SI or body mass index. FEV 1 decline was -13.4 mL/year (-42.8; +11.9) and was greater in women (-29.3 mL/year, (-59.7; -11.9), vs -2.0 mL/year (-26.9; +25.4), p=0.002). Three patients had severe respiratory failure., Conclusions: Alteration of respiratory function in adults with PCD is heterogeneous and usually moderate but appears more severe in women and in patients with chronic PA infection. Only 4% of patients develop chronic respiratory failure., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose of Review: Successful ambulatory care implementation should combine both medical and organizational features. These two components are closely interrelated. Only optimal organization, part of a quality management program, will allow us to perform safe medical procedures and provide good patient satisfaction. This review is intended to update organizational concepts that could improve ambulatory surgery center efficiency., Recent Findings: Current organizational concepts are based on the implementation of a dedicated pathway that could be divided into sequential steps, wherein the concepts of flow time and throughput should be applied. Wasted times have to be evaluated and suppressed, so patients have to spend only the minimum required time at each step. A 'forward pathway' would allow maintaining unidirectional patients' flow to avoid any blockade and to build sequential surgical program planning. These processes are easier to implement in dedicated facilities, managed by a dedicated staff, after extensive patient preoperative information, and with the use of numeric information systems., Summary: Organizational feature in ambulatory surgery center is a major determinant of patient flow, activity, resource utilization, safety, and patient satisfaction. Most of these basic principles may contribute to improve the quality of care that can also be of benefit to conventional surgical activity.

Patients flow in outpatient surgical unit is a major issue with regards to resource utilization, overall case load and patient satisfaction. An electronic Radio Frequency Identification Device (RFID) was used to document the overall time spent by the patients between their admission and discharge from the unit. The objective of this study was to evaluate how a RFID-based data collection system could provide an accurate prediction of the actual time for the patient to be discharged from the ambulatory surgical unit after surgery. This is an observational prospective evaluation carried out in an academic ambulatory surgery center (ASC). Data on length of stay at each step of the patient care, from admission to discharge, were recorded by a RFID device and analyzed according to the type of surgical procedure, the surgeon and the anesthetic technique. Based on these initial data (n = 1520), patients were scheduled in a sequential manner according to the expected duration of the previous case. The primary endpoint was the difference between actual and predicted time of discharge from the unit. A total of 414 consecutive patients were prospectively evaluated. One hundred seventy four patients (42%) were discharged at the predicted time ± 30 min. Only 24% were discharged behind predicted schedule. Using an automatic record of patient's length of stay would allow an accurate prediction of the discharge time according to the type of surgery, the surgeon and the anesthetic procedure.

Purpose: To assess the suitability of ultrasound-guided (USG), single-injection distal block(s) for pain management after outpatient hand and wrist bone surgery., Methods: We conducted a retrospective review of 125 of 198 consecutive ambulatory surgery patients who underwent hand and wrist bone surgery between June 2010 and January 2012. All patients received a USG axillary block using a short-acting local anesthetic (lidocaine) and secondary 1, 2, or 3 (median, radial, or ulnar) USG distal analgesic block(s) using a long-acting local anesthetic (ropivacaine). All patients were contacted by phone on the first postoperative day. All patients received a concomitant prescription of acetaminophen and nonsteroidal anti-inflammatory drugs with opioids as a rescue treatment. Effectiveness and duration of the distal nerve blocks, compliance with analgesic treatment and rescue opioids requirement, opioid-related side effects, prolonged upper limb motor block, quality of sleep on first postoperative night, and patient satisfaction were evaluated., Results: Most distal analgesic blocks were effective (120 of 125; 96%), with an average duration of nearly 12 hours On the first day after surgery, 28 patients (23%) had a numeric verbal scale greater than 3, although 14 of them had taken the rescue opioids. No patient reported prolonged motor blockade or insensate limb. Opioid-related side effects occurred in 23% of patients., Conclusions: After hand and wrist bone surgery, USG selective distal blocks using a long-acting local anesthetic, combined with oral analgesics, were effective in a large majority of patients. However, pain control was suboptimal for some especially painful procedures such as wrist surgery, trapeziometacarpal arthrodesis, and finger amputation., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Objective: TAP is a regional anaesthetic technique where local anaesthesic (LA) is injected between the internal oblique and the transversus abdominis muscles in order to block intercostal nerves. The technique originally described, is based on the identification of the lumbar triangle of Petit as the area where to insert the needle before the LA injection. We performed a study to determine, using ultrasonography, the actual location of the LA when TAP block was performed using landmark-based technique., Study Design: Prospective and observational study., Methods: Fifty-two patients scheduled for ileostomy closure surgery under general anaesthesia received a TAP block (20 mL 0.75% ropivacaine) based on standard anatomical landmarks technique. Ultrasonography was used immediately after the block to determine the LA placement. Failed blocks were considered when the patient required intravenous morphine in the immediate postoperative period for pain localised at the operative site., Results: LA solution was injected in the right place in 14 cases out of 52. Only one of these patient received morphine in the postoperative period. In the remaining 38 blocks, the LA was administered in adjacent anatomical structures and 25 failed. Two injections in the peritoneum were observed., Conclusion: The localization of LA after the TAP block being performed by landmark-based techniques is highly variable. In the majority of patients, the LA was injected in adjacent anatomical structures with unpredictable block results. This may promote the use of ultrasound-guided technique to perform the TAP block., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Purpose: This study measured time and ability to walk in PACU after unilateral spinal anaesthesia., Methods: Orthopaedic adult patients ASA 1-2, in the lateral decubitus position and placed on the operative side, received via a 25-gauge Whitacre needle 5 mg of 0.5% bupivacaine plus 2.5 microg of sufentanil. Lateral decubitus was maintained for 15 minutes. Time from the spinal injection to eligibility for discharge was recorded. Discharge criteria were stable hemodynamic and ability to walk without crutches., Results: One hundred consecutive patients (38 females), 48 +/- 15 years-old were included. Unilateral sensory block was noted in 70% of patients. The maximum level of sensory block was at L1-T12 in 30 patients, at T11-T10 in 55 patients, at T9-T8 in 6 patients and at T7-T6 in 9. Criteria for PACU discharge were completed at 140 +/- 14 min (extremes: 55-235). All patients were discharged home uneventfully., Conclusion: Unilateral spinal anesthesia combining bupivacaine and sufentanil gives fast ability to walk for discharge.

Continuous surveillance of both regional and general temperatures is of great interest in anaesthesia and intensive care. After a brief review of temperature regulation and the value of temperature control, the authors suggest a simple and reliable method of surveillance. This uses Chromel/Alumel thermocouples connected to a central device used to store the information. An experimental clinical study involved the assessment of 3 different anaesthetic protocols: Taractan-Palfium; Droleptan-Phenoperidine, Fentanyl only. These measurements were made in 30 young subjects undergoing a maxillofacial surgical procedure under identical conditions. The parameters studied were central temperature (rectal) and skin temperature of the index finger. With regard to peripheral temperature curves the results showed a first phase consisting of fall followed by a second phase characterised by a sudden increase up to a plateau. This plateau (3rd phase) persisted as long as the subject slept. The 4th phase, when peripheral temperature fell suddenly to a level sometimes lower than the initial temperature represented one of the first signs of awakening. As far as central temperature was concerned it fell in a linear fashion for all curves. Comparing the different curves obtained, the authors conclude by noting that the more vasoplegic the anaesthetic protocol, the higher the induction peak of the second phase of peripheral temperature pattern, but also that the fall in central temperature was marked. The authors feel that an anaesthetic which is biologically satisfactory and at the same time produces an overall fall in the production of heat without causing chills avoids the development of vasoconstrictor reactions between the care and the surface which are reflected by a decrease in the gradient between central and peripheral temperatures.

We describe the disaster medicine training program that has been developed in France by the anesthesia-reanimation specialists who provide emergency medical services. The diploma course is presented twice yearly over a two-week period to physicians of all disciplines. The 71-hour didactic program covers the background of disasters, various plans and strategies, tactics and logistics, techniques, and victim assessment and treatment. This is followed by a field exercise. Graduates then participate in a full-scale mock disaster exercise that lasts two days to one week. The development of such a course illustrates the attention that nations worldwide are giving to specialized physician training in disaster preparedness.