Whole-body fasciculation detection in amyotrophic lateral sclerosis using motor unit MRI.

OBJECTIVE: Compare fasciculation rates between amyotrophic lateral sclerosis (ALS) patients and healthy controls in body regions relevant for diagnosing ALS using motor unit MRI (MUMRI) at baseline and 6 months follow-up, and relate this to single-channel surface EMG (SEMG). METHODS: Tongue, biceps brachii, paraspinals and lower legs were assessed with MUMRI and biceps brachii and soleus with SEMG in 10 healthy controls and 10 patients (9 typical ALS, 1 primary lateral sclerosis [PLS]). RESULTS: MUMRI-detected fasciculation rates in typical ALS patients were higher compared to healthy controls for biceps brachii (2.40 ± 1.90 cm-3min-1vs. 0.04 ± 0.10 cm-3min-1, p = 0.004), paraspinals (1.14 ± 1.61 cm-3min-1vs. 0.02 ± 0.02 cm-3min-1, p = 0.016) and lower legs (1.42 ± 1.27 cm-3min-1vs. 0.13 ± 0.10 cm-3min-1, p = 0.004), but not tongue (1.41 ± 1.94 cm-3min-1vs. 0.18 ± 0.18 cm-3min-1, p = 0.556). The PLS patient showed no fasciculation. At baseline, 6/9 ALS patients had increased fasciculation rates compared to healthy controls in at least 2 body regions. At follow-up every patient had increased fasciculation rates in at least 2 body regions. The MUMRI-detected fasciculation rate correlated with SEMG-detected fasciculation rates (τ = 0.475, p = 0.006). CONCLUSION: MUMRI can non-invasively image fasciculation in multiple body regions and appears sensitive to disease progression in individual patients. SIGNIFICANCE: MUMRI has potential as diagnostic tool for ALS.

[Uses of 3D printing and Bioprinting for pre-implant bone reconstruction in Oral Surgery]. / Impression 3D et bioimpression pour la régénération osseuse en chirurgie orale.

Pre-implant bone surgery in oral surgery allows to reconstruct maxillary atrophies related to traumatic, infectious or tumoral processes. In this context, the ideal biomaterial remains autogenous bone, but biomaterials (of natural or synthetic origin) allow to limit the morbidity linked to bone harvesting, and to simplify these surgical procedures. In this article, we illustrate how 3D printing technologies can be used as an adjuvant to treat bone defects of complex shape or to create anatomical models used to plan interventions. Finally, some perspectives brought by tissue engineering and bioprinting (creation of complex in vitro models) are presented.

Title: Impression 3D et bioimpression pour la régénération osseuse en chirurgie orale. Abstract: La chirurgie osseuse pré-implantaire en chirurgie orale permet de reconstruire les atrophies des maxillaires en rapport avec des processus traumatiques, infectieux ou tumoraux. Dans ce contexte, le biomatériau idéal reste l'os autogène mais les biomatériaux (d'origine naturelle ou synthétique) permettent de limiter la morbidité liée aux prélèvements osseux et de simplifier ces interventions chirurgicales. Dans cet article, nous illustrons l'apport récent de l'impression 3D dans ce contexte pour traiter des défauts osseux de forme complexe ou pour créer des modèles anatomiques servant à planifier les interventions. Enfin, les perspectives apportées par l'ingénierie tissulaire et la bioimpression (création de modèles in vitro complexes) sont détaillées.

Pulmonary Telerehabilitation for People With Chronic Obstructive Pulmonary Disease in Brazil: A Mixed-Methods Feasibility Study.

This study assessed the feasibility of pulmonary telerehabilitation‧s (PTR) acceptability, implementation, practicality, and adaptation for people with Chronic Obstructive Pulmonary Disease (COPD) in Brazil. It also explored associations with clinical and socioeconomic features of Brazilians with COPD. This mixed-method study included thirty-one participants with COPD (age 62±10 years; FEV1= 72±14% predicted). Most participants (74.2%) reported good PTR session acceptability on the System Usability Scale and scores of 4.6±0.3 and 4.5±0.6 on a 1-5 Likert-type scale of implementation and practicality, respectively. Participants suggested adaptations for better comfort on the exercise bike and varying exercise modalities. PTR acceptability was associated with participants' younger age (rs=-0.57, p<0.01) and higher education (rs=0.51, p<0.01). PTR is feasible for people with COPD in Brazil regarding acceptability, implementation, practicality, and adaptation. Younger age and higher educational level are associated with greater PTR acceptability.

AMEBaS: Automatic Midline Extraction and Background Subtraction of Ratiometric Fluorescence Time-Lapses of Polarized Single Cells.

Cell polarity is a macroscopic phenomenon established by a collection of spatially concentrated molecules and structures that culminate in the emergence of specialized domains at the subcellular level. It is associated with developing asymmetric morphological structures that underlie key biological functions such as cell division, growth, and migration. In addition, the disruption of cell polarity has been linked to tissue-related disorders such as cancer and gastric dysplasia. Current methods to evaluate the spatiotemporal dynamics of fluorescent reporters in individual polarized cells often involve manual steps to trace a midline along the cells' major axis, which is time consuming and prone to strong biases. Furthermore, although ratiometric analysis can correct the uneven distribution of reporter molecules using two fluorescence channels, background subtraction techniques are frequently arbitrary and lack statistical support. This manuscript introduces a novel computational pipeline to automate and quantify the spatiotemporal behavior of single cells using a model of cell polarity: pollen tube/root hair growth and cytosolic ion dynamics. A three-step algorithm was developed to process ratiometric images and extract a quantitative representation of intracellular dynamics and growth. The first step segments the cell from the background, producing a binary mask through a thresholding technique in the pixel intensity space. The second step traces a path through the midline of the cell through a skeletonization operation. Finally, the third step provides the processed data as a ratiometric timelapse and yields a ratiometric kymograph (i.e., a 1D spatial profile through time). Data from ratiometric images acquired with genetically encoded fluorescent reporters from growing pollen tubes were used to benchmark the method. This pipeline allows for faster, less biased, and more accurate representation of the spatiotemporal dynamics along the midline of polarized cells, thus advancing the quantitative toolkit available to investigate cell polarity. The AMEBaS Python source code is available at: https://github.com/badain/amebas.git.

A Prototype Implantable Artificial Bronchus Reduces Lung Hyperinflation in Recently Deceased Patients with Emphysema.

BACKGROUND: Several minimally invasive treatments have been offered to patients with severe emphysema over the last two decades. Currently, endobronchial valves (EBVs) are the only approved therapeutic option, but this method has drawbacks: only a few can undergo this therapy and the incidence of pneumothorax remains high. A minimally invasive technique, appropriate for a broader patient population and posing fewer risks, would represent a desirable alternative to improve lung function in these patients. OBJECTIVE: The objective of this study was to demonstrate whether a new prototype implantable artificial bronchus (IAB) releases trapped air from the lungs of recently deceased patients with emphysema. METHOD: Seven recently deceased patients with emphysema were mechanically ventilated and the respiratory rate increased from 12 bpm (resting) to 30 bpm (exercise), inducing air trapping and dynamic hyperinflation. This protocol was performed twice, before and after IAB placement. Ventilation parameters and the fraction of inspired oxygen were similar in all patients. Respiratory system plateau pressure (Pplat,rs) and intrinsic positive end-expiratory pressure (iPEEP) were measured. RESULTS: IAB implantation significantly reduced Pplat,rs (p = 0.017) in 6 of 7 deceased patients with emphysema and iPEEP (p = 0.03) in 5 of 7 patients. CONCLUSIONS: Placement of one or two IABs in segmental bronchi (up to 15th generation) proved to be feasible and improved lung function. These findings should provide a basis for subsequent clinical studies to assess the safety and efficacy of IAB in patients with emphysema, as well as identify short- and long-term effects of this innovative procedure.

A survey of current practice in genetic testing in amyotrophic lateral sclerosis in the UK and Republic of Ireland: implications for future planning.

Objective: To determine the current practice in genetic testing for patients with apparently sporadic motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) and asymptomatic at-risk relatives of familial MND/ALS patients seen in specialized care centers in the UK. Methods: An online survey with 10 questions distributed to specialist healthcare professionals with a role in requesting genetic testing working at MND/ALS care centers. Results: Considerable variation in practice was found. Almost 30% of respondents reported some discomfort in discussing genetic testing with MND/ALS patients and a majority (77%) did not think that all patients with apparently sporadic disease should be routinely offered genetic testing at present. Particular concerns were identified in relation to testing asymptomatic at-risk individuals and the majority view was that clinical genetics services should have a role in supporting genetic testing in MND/ALS, especially in asymptomatic individuals at-risk of carrying pathogenic variants. Conclusions: Variation in practice in genetic testing among MND/ALS clinics may be driven by differences in experience and perceived competence, compounded by the increasing complexity of the genetic underpinnings of MND/ALS. Clear and accessible guidelines for referral pathways between MND/ALS clinics and clinical genetics may be the best way to standardize and improve current practice, ensuring that patients and relatives receive optimal and geographically equitable support.

Explaining predictive factors in patient pathways using autoencoders.

This paper introduces an end-to-end methodology to predict a pathway-related outcome and identifying predictive factors using autoencoders. A formal description of autoencoders for explainable binary predictions is presented, along with two objective functions that allows for filtering and inverting negative examples during training. A methodology to model and transform complex medical event logs is also proposed, which keeps the pathway information in terms of events and time, as well as the hierarchy information carried in medical codes. A case study is presented, in which the short-term mortality after the implementation of an Implantable Cardioverter-Defibrillator is predicted. Proposed methodologies have been tested and compared to other predictive methods, both explainable and not explainable. Results show the competitiveness of the method in terms of performances, particularly the use of a Variational Auto Encoder with an inverse objective function. Finally, the explainability of the method has been demonstrated, allowing for the identification of interesting predictive factors validated using relative risks.

In vitrolong term differentiation and functionality of three-dimensional bioprinted primary human hepatocytes: application forin vivoengraftment.

In recent decades, 3Din vitrocultures of primary human hepatocytes (PHHs) have been increasingly developed to establish models capable of faithfully mimicking main liver functions. The use of 3D bioprinting, capable of recreating structures composed of cells embedded in matrix with controlled microarchitectures, is an emergent key feature for tissue engineering. In this work, we used an extrusion-based system to print PHH in a methacrylated gelatin (GelMa) matrix. PHH bioprinted in GelMa rapidly organized into polarized hollow spheroids and were viable for at least 28 d of culture. These PHH were highly differentiated with maintenance of liver differentiation genes over time, as demonstrated by transcriptomic analysis and functional approaches. The cells were polarized with localization of apico/canalicular regions, and displayed activities of phase I and II biotransformation enzymes that could be regulated by inducers. Furthermore, the implantation of the bioprinted structures in mice demonstrated their capability to vascularize, and their ability to maintain human hepatic specific functions for at least 28 d was illustrated by albumin secretion and debrisoquine metabolism. This model could hold great promise for human liver tissue generation and its use in future biotechnological developments.

Electrodiagnostic findings in facial onset sensory motor neuronopathy (FOSMN).

OBJECTIVE: To determine the electrodiagnostic characteristics of facial onset sensory and motor neuronopathy (FOSMN). METHODS: Electrophysiological data from 10 FOSMN patients in Newcastle-upon-Tyne and Sydney were reviewed. Relevant literature was reviewed. RESULTS: Findings on standard electrophysiological assessment were in broad agreement with those published: blink reflexes were abnormal in all but one patient; sensory nerve action potentials were reduced but compound muscle action potentials preserved; mixed acute and chronic neurogenic change was identified on needle electromyography in bulbar and cervico-thoracic muscles in approximately 50% of patients. Upper limb somatosensory evoked potential (SEP) central conduction times were increased (n = 4) and progressed on repeat testing (n = 3). Upper motor neuron dysfunction was revealed by several measures [ipsilateral motor evoked potentials (MEPs) (n = 1); reduced short interval intra-cortical inhibition on threshold-tracking transcranial magnetic stimulation (n = 2); absent beta-band intermuscular coherence (n = 3)]. CONCLUSIONS: Electrodiagnostic investigation of FOSMN should include blink reflex testing, SEPs and tests of upper motor neuron function. The combination of progressive lower motor neuron disease and upper motor neuron disease on neurophysiological investigation provides further support for the contention that FOSMN is a rare variant of motor neurone disease. SIGNIFICANCE: These findings will aid the neurologist and neurophysiologist in making a confident diagnosis of FOSMN, thus expediting appropriate care.

In vitroandin vivocharacterization of a novel tricalcium silicate-based ink for bone regeneration using laser-assisted bioprinting.

Grafts aside, current strategies employed to overcome bone loss still fail to reproduce native tissue physiology. Among the emerging bioprinting strategies, laser-assisted bioprinting (LAB) offers very high resolution, allowing designing micrometric patterns in a contactless manner, providing a reproducible tool to test ink formulation. To this date, no LAB associated ink succeeded to provide a reproduciblead integrumbone regeneration on a murine calvaria critical size defect model. Using the Conformité Européenne (CE) approved BioRoot RCS® as a mineral addition to a collagen-enriched ink compatible with LAB, the present study describes the process of the development of a solidifying tricalcium silicate-based ink as a new bone repair promoting substrates in a LAB model. This ink formulation was mechanically characterized by rheology to adjust it for LAB. Printed aside stromal cells from apical papilla (SCAPs), this ink demonstrated a great cytocompatibility, with significantin vitropositive impact upon cell motility, and an early osteogenic differentiation response in the absence of another stimulus. Results indicated that thein vivoapplication of this new ink formulation to regenerate critical size bone defect tends to promote the formation of bone volume fraction without affecting the vascularization of the neo-formed tissue. The use of LAB techniques with this ink failed to demonstrate a complete bone repair, whether SCAPs were printed or not of at its direct proximity. The relevance of the properties of this specific ink formulation would therefore rely on the quantity appliedin situas a defect filler rather than its cell modulation properties observedin vitro. For the first time, a tricalcium silicate-based printed ink, based on rheological analysis, was characterizedin vitroandin vivo, giving valuable information to reach complete bone regeneration through formulation updates. This LAB-based process could be generalized to normalize the characterization of candidate ink for bone regeneration.

Expert Statement: Pneumothorax Associated with One-Way Valve Therapy for Emphysema: 2020 Update.

For selected patients with advanced emphysema, bronchoscopic lung volume reduction with one-way valves can lead to clinically relevant improvements of airflow obstruction, hyperinflation, exercise capacity, and quality of life. The most common complication of this procedure is pneumothorax with a prevalence of up to ±34% of the treated patients. Patients who develop a pneumothorax also experience meaningful clinical benefits once the pneumothorax is resolved. Timely resolution of a post-valve treatment pneumothorax requires skilled and adequate pneumothorax management. This expert panel statement is an updated recommendation of the 2014 statement developed to help guide pneumothorax management after valve placement. Additionally, mechanisms for pneumothorax development, risk assessment, prevention of pneumothorax, and outcomes after pneumothorax are addressed. This recommendation is based on a combination of the current scientific literature and expert opinion, which was obtained through a modified Delphi method.

A comparative analysis between atraumatic and conventional anesthetic techniques in surgical removal of upper third molars / Análise comparativa entre a técnica anestésica atraumática e convencional em cirurgia para remopao dos terceiros molares superiores

ABSTRACT Pain control is essential in dental practice, and can be accomplished through various techniques. This study seeks to compare atraumatic and conventional anesthetic techniques, applied during surgeries to remove upper third molars. The endpoints evaluated were pain indices, patient satisfaction and anesthetic efficacy. A random parallel split-mouth clinical trial was conducted with 14 patients. Group A received atraumatic anesthesia without a needle (Comfort-in®) and group B received conventional anesthesia by blocking the posterior superior alveolar nerve (PSAN) and Greater Palatine Nerve (GPN). A Visual Analogue Scale (VAS) was used to assess pain. A significantly (p<0.001) lower perception ofpain was observed among individuals who received the atraumatic technique. In 71% of cases, it was necessary to supplement the anesthesia during the procedure. Even considering the need for additional anesthesia, the Comfort-in® technique was more accepted by patients with regard to pain perception than the conventional manual technique.

RESUMO O controle da dor é fundamental na prática odontológica, po-dendo ser feito a partir de várias técnicas. Este estudo visa comparar as técnicas anestésicas atraumática e convencional, aplicadas durante cirurgias para remover terceiros molares superiores. Os pontos avaliados foram índice de dor, satisfaqao do paciente e eficácia anestésica. Um ensaio clínico randomi-zado, paralelo, boca dividida, foi conduzido com 14 participantes. O grupo A recebeu anestesia atraumática sem agulha (Comfort-in®) e o grupo B anestesia convencional por meio de bloqueio do nervo alveolar superior posterior (NASP) e nervo palatino maior (NPM). Uma Escala Visual Analógica (EVA) foi utilizada para avaliar a dor. Uma significativa (p<0,001) menor percepção de dor entre os individuos que receberam a técnica atraumática foi observada. Em 71% dos casos, fez-se necessària a complementação da anestesia durante a realiza-ção do procedimento. Mesmo considerando a necessidade de anestesia adicional, a técnica empregando o sistema Comfort-in® teve maior aceitação dos pacientes quando comparado à técnica manual convencional, no que se refere a percepção de dor, ainda que considerando a necessidade de complementação da anestesia.

"Bow-tie" optimal pathway discovery analysis of sepsis hospital admissions using the Hospital Episode Statistics database in England.

OBJECTIVE: The "Bow-tie" optimal pathway discovery analysis uses large clinical event datasets to map clinical pathways and to visualize risks (improvement opportunities) before, and outcomes after, a specific clinical event. This proof-of-concept study assesses the use of NHS Hospital Episode Statistics (HES) in England as a potential clinical event dataset for this pathway discovery analysis approach. MATERIALS AND METHODS: A metaheuristic optimization algorithm was used to perform the "bow-tie" analysis on HES event log data for sepsis (ICD-10 A40/A41) in 2016. Analysis of hospital episodes across inpatient and outpatient departments was performed for the period 730 days before and 365 days after the index sepsis hospitalization event. RESULTS: HES data captured a sepsis event for 76 523 individuals (>13 years), relating to 580 000 coded events (across 220 sepsis and non-sepsis event classes). The "bow-tie" analysis identified several diagnoses that most frequently preceded hospitalization for sepsis, in line with the expectation that sepsis most frequently occurs in vulnerable populations. A diagnosis of pneumonia (5 290 patients) and urinary tract infections (UTIs; 2 057 patients) most often preceded the sepsis event, with recurrent UTIs acting as a potential indicative risk factor for sepsis. DISCUSSION: This proof-of-concept study demonstrates that a "bow-tie" pathway discovery analysis of the HES database can be undertaken and provides clinical insights that, with further study, could help improve the identification and management of sepsis. The algorithm can now be more widely applied to HES data to undertake targeted clinical pathway analysis across multiple healthcare conditions.

TDP-43 proteinopathies: a new wave of neurodegenerative diseases.

Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. For instance, the majority of patients with sporadic amyotrophic lateral sclerosis (up to 97%) and a substantial proportion of patients with frontotemporal lobar degeneration (~45%) exhibit TDP-43 positive neuronal inclusions, suggesting a role for this protein in disease pathogenesis. In addition, TDP-43 inclusions are evident in familial ALS phenotypes linked to multiple gene mutations including the TDP-43 gene coding (TARDBP) and unrelated genes (eg, C9orf72). While TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism, determining the pathophysiological mechanisms through which TDP-43 mediates neurodegeneration appears complex, and unravelling these molecular processes seems critical for the development of effective therapies. This review highlights the key physiological functions of the TDP-43 protein, while considering an expanding spectrum of neurodegenerative diseases associated with pathogenic TDP-43 deposition, and dissecting key molecular pathways through which TDP-43 may mediate neurodegeneration.

Automatic and Explainable Labeling of Medical Event Logs With Autoencoding.

Process mining is a suitable method for knowledge extraction from patient pathways. Structured in event logs, medical events are complex, often described using various medical codes. An efficient labeling of these events before applying process mining analysis is challenging. This paper presents an innovative methodology to handle the complexity of events in medical event logs. Based on autoencoding, accurate labels are created by clustering similar events in latent space. Moreover, the explanation of created labels is provided by the decoding of its corresponding events. Tested on synthetic events, the method is able to find hidden clusters on sparse binary data, as well as accurately explain created labels. A case study on real healthcare data is performed. Results confirm the suitability of the method to extract knowledge from complex event logs representing patient pathways.

Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial.

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation.Objectives:Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported.Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George's Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy).Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P < 0.05 and P < 0.001, respectively). Reduction in CAT was through improvements in breathlessness (P < 0.05), energy level (P < 0.05), activities (P < 0.001), and increased confidence when leaving home (P < 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved (P < 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio.Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months.Clinical trial registered with www.clinicaltrials.gov (NCT01796392).

A comparative analysis between atraumatic and conventional anesthetic techniques in surgical removal of upper third molars.

Pain control is essential in dental practice, and can be accomplished through various techniques. This study seeks to compare atraumatic and conventional anesthetic techniques, applied during surgeries to remove upper third molars. The endpoints evaluated were pain indices, patient satisfaction and anesthetic efficacy. A random parallel split-mouth clinical trial was conducted with 14 patients. Group A received atraumatic anesthesia without a needle (Comfort-in®) and group B received conventional anesthesia by blocking the posterior superior alveolar nerve (PSAN) and Greater Palatine Nerve (GPN). A Visual Analogue Scale (VAS) was used to assess pain. A significantly (p<0.001) lower perception of pain was observed among individuals who received the atraumatic technique. In 71% of cases, it was necessary to supplement the anesthesia during the procedure. Even considering the need for additional anesthesia, the Comfort-in® technique was more accepted by patients with regard to pain perception than the conventional manual technique.

O controle da dor é fundamental na prática odontológica, podendo ser feito a partir de várias técnicas. Este estudo visa comparar as técnicas anestésicas atraumática e convencional, aplicadas durante cirurgias para remover terceiros molares superiores. Os pontos avaliados foram índice de dor, satisfação do paciente e eficácia anestésica. Um ensaio clínico randomizado, paralelo, boca dividida, foi conduzido com 14 participantes. O grupo A recebeu anestesia atraumática sem agulha (Comfort-in®) e o grupo B anestesia convencional por meio de bloqueio do nervo alveolar superior posterior (NASP) e nervo palatino maior (NPM). Uma Escala Visual Analógica (EVA) foi utilizada para avaliar a dor. Uma significativa (p<0,001) menor percepção de dor entre os indivíduos que receberam a técnica atraumática foi observada. Em 71% dos casos, fez-se necessária a complementação da anestesia durante a realização do procedimento. Mesmo considerando a necessidade de anestesia adicional, a técnica empregando o sistema Comfort- in® teve maior aceitação dos pacientes quando comparado à técnica manual convencional, no que se refere a percepção de dor, ainda que considerando a necessidade de complementação da anestesia.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Non-Answered Questions in Patients with Endobronchial Valve Placement for Lung Volume Reduction.

Endoscopic lung volume reduction is a minimally invasive procedure performed to reduce the space occupied by the emphysemas' lobes. This procedure has been demonstrated to be beneficial for patients with advanced chronic obstructive pulmonary disease and severe hyperinflation. The use of endobronchial valves is increasing, as well as the number of reports of adverse events. The most common complications after the procedure are a pneumothorax, bleeding, infections, the need for valve removal, and valve expulsion. We have recently treated a patient who achieved immediate left upper lobe atelectasis but developed a pneumothorax on the 6th day and near-fatal kinking of the left lower lobe bronchus. This patient had asphyctic episodes probably due to a functional left pneumonectomy. We should consider this unusual complication in patients undergoing endoscopic lung volume reduction whose condition worsens after achieving complete lobar atelectasis.