Innovation in rigid bronchoscopy-past, present, and future.

German laryngologist Gustav Killian performed the first "Direkte Bronchoskopie" using a rigid bronchoscope to extract a foreign airway body from the right main bronchus over a hundred years ago, transforming the practice of respiratory medicine. The procedure instantaneously became popular throughout the world. Chevalier Jackson Sr from the United States further advanced the instrument, technique, safety, and application. In the 1960s, Professors Harold H. Hopkins and N.S. Kapany introduced optical rods as well as fiberoptics that led Karl Storz to develop the cold light system improving endoluminal illumination, achievements that ushered in the modern era of flexible endoscopy. Several diagnostic and therapeutic procedures became possible such as transbronchial needle biopsy, transbronchial lung biopsy, airway electrosurgery, or cryotherapy. Dr. Jean-François Dumon from France advanced the use of Nd-YAG laser in the endobronchial tree and created the dedicated Dumon silicone stent introducing the whole new field of interventional pulmonology (IP). This major milestone revitalized interest in rigid bronchoscopy (RB). Now, advancements are being made in stenting, instrumentation, and education. RB robotic technology advancements are currently anticipated and can potentially revolutionize the practice of pulmonary medicine. In this review, we describe some of the most substantial advances related to RB from its beginning to the modern era.

ModInterv COVID-19: An online platform to monitor the evolution of epidemic curves.

We present the software ModInterv as an informatics tool to monitor, in an automated and user-friendly manner, the evolution and trend of COVID-19 epidemic curves, both for cases and deaths. The ModInterv software uses parametric generalized growth models, together with LOWESS regression analysis, to fit epidemic curves with multiple waves of infections for countries around the world as well as for states and cities in Brazil and the USA. The software automatically accesses publicly available COVID-19 databases maintained by the Johns Hopkins University (for countries as well as states and cities in the USA) and the Federal University of Viçosa (for states and cities in Brazil). The richness of the implemented models lies in the possibility of quantitatively and reliably detecting the distinct acceleration regimes of the disease. We describe the backend structure of software as well as its practical use. The software helps the user not only to understand the current stage of the epidemic in a chosen location but also to make short term predictions as to how the curves may evolve. The app is freely available on the internet (http://fisica.ufpr.br/modinterv), thus making a sophisticated mathematical analysis of epidemic data readily accessible to any interested user.

NSCLC in the Era of Targeted and Immunotherapy: What Every Pulmonologist Must Know.

The treatment of non-small cell lung cancer has dramatically changed over the last decade through the use of targeted therapies and immunotherapies. Implementation of these treatment regimens relies on detailed knowledge regarding each tumor's specific genomic profile, underscoring the necessity of obtaining superior diagnostic tissue specimens. While these treatment approaches are commonly utilized in the metastatic setting, approval among earlier-stage disease will continue to rise, highlighting the importance of early and comprehensive biomarker testing at the time of diagnosis for all patients. Pulmonologists play an integral role in the diagnosis and staging of non-small cell lung cancer via sophisticated tissue sampling techniques. This multifaceted review will highlight current indications for the use of targeted therapies and immunotherapies in non-small cell lung cancer and will outline the quality of various diagnostic approaches and subsequent success of tissue biomarker testing. Pulmonologist-specific methods, including endobronchial ultrasound and guided bronchoscopy, will be examined as well as other modalities such as CT-guided transthoracic biopsy and more.

Analysis of Mechanoreceptors and Free Nerve Endings of the Transverse Carpal Ligament.

Background: The treatment of carpal tunnel syndrome (CTS) by sectioning the transverse carpal ligament (TCL) is not exempt from complications. Some nerve branches may be damaged by the incision. The aim of this study is to identify and map the TCL nerve endings, serving as a guide for sectioning this structure in a zone with less nerve ending density. Methods: Ten TCLs were obtained from fresh frozen cadavers. The TCLs were measured, divided into 3 equal bands (radial, central, and ulnar), and submitted to cryostat sectioning. The sections were subjected to immunofluorescence with the protein gene product (PGP) 9.5 and confocal microscopy analysis. Results: All the specimens contained type I and type IV mechanoreceptors. Neural elements occupied 0.695 ± 0.056% of the ligament area. The density of the neural elements was greater in the radial, followed by the ulnar and central bands, with 0.730 ± 0.083%, 0.686 ± 0.009%, and 0.669 ± 0.031%, respectively. Conclusion: The present findings suggest that the region with the least potential for neural element injury during TCL release is the central third near the transition with the ulnar third. When performed distally to proximally with a slight inclination from the radial to the ulnar, this release compromises the lowest nerve element density. Topographically, the proximal limit of the release is the distal wrist crease, while the distal limit is the intersection of Kaplan cardinal line and the axis of the third webspace.

Short-term Endoscopic Outcomes of Balloon and Rigid Bronchoplasty in the Management of Benign Subglottic and Tracheal Stenosis.

BACKGROUND: Endoscopic therapies are firmly established in the management algorithm of benign subglottic and tracheal stenosis (SGTS). The optimal dilation strategy, however, has yet to be elucidated. The objective of this study was to compare the efficacy and safety of balloon versus rigid bronchoplasty in the treatment of benign SGTS. METHODS: De novo cases of benign SGTS at our institution over a 9-year period were retrospectively identified. Patients were divided into 2 groups based on the initial dilation strategy of balloon or rigid bronchoplasty. Demographics, clinical findings, concurrent interventions, lesion characteristics, and complications were analyzed. Two reviewers independently assigned an index and follow-up endoscopic stenosis grade for each case. The mean stenosis grade at follow-up in both groups was then calculated and compared. RESULTS: Sixty-three patients with benign SGTS were included. Most stenoses in the rigid (80%) and balloon (63%) bronchoplasty groups were complex ( P =0.174). In addition, 94% (59/63) of index stenoses were classified as Cotton Myer Grade 3. At follow-up, no significant difference was found in the mean stenosis grade between dilation strategies (1.97 vs. 2.2, P =0.287). Furthermore, no procedural-related complications were observed in either group. CONCLUSION: Balloon and rigid bronchoplasty are safe and effective endoscopic tools in the early management of benign SGTS. A multimodality approach centered around mucosal sparing techniques remains vitally important to the overall and likely long-term success of treating this challenging disease entity.

ModInterv: An automated online software for modeling epidemics.

The COVID-19 pandemic has proven the importance of mathematical tools to understand the evolution of epidemic outbreaks and provide reliable information to the general public and health authorities. In this perspective, we have developed ModInterv, an online software that applies growth models to monitor the evolution of the COVID-19 epidemic in locations chosen by the user among countries worldwide or states and cities in the USA or Brazil. This paper describes the software capabilities and its use both in recent research works and by technical committees assisting government authorities. Possible applications to other epidemics are also briefly discussed.

Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.

Subclinical Burkholderia pseudomallei Infection Associated with Travel to the British Virgin Islands.

Phylogenetic analysis of a clinical isolate associated with subclinical Burkholderia pseudomallei infection revealed probable exposure in the British Virgin Islands, where reported infections are limited. Clinicians should consider this geographic distribution when evaluating possible infection among persons with compatible travel history.

Radial endobronchial ultrasound-assisted transbronchial needle aspiration for pulmonary peripheral lesions in the segmental bronchi adjacent to the central airway.

BACKGROUND: Tissue samples from lesions located in the 3rd to 5th segmental bronchi are challenging to obtain. In this retrospective study, we aimed to evaluate the diagnostic rate of pulmonary peripheral lesions located in the 3rd to 5th segmental bronchi, near the inner field of lung on the computed tomography (CT) image and outside the bronchus, using radial endobronchial ultrasound (REBUS) followed by transbronchial needle aspiration (TBNA). METHODS: This retrospective study enrolled patients whose preoperative CT examinations showed a lesion located in the segmental bronchi (3rd to 5th), yet adjacent to the inner field of lung on the CT image. REBUS followed by TBNA was used to acquire tissue samples from these lesions. A bronchoscope was used to reach the bronchi surrounding the lesion, and an ultrasound probe was used to determine the lesion's location. Then, the ultrasound probe was withdrawn, and puncture was performed at the location that was determined by ultrasound. The tissue specimens obtained were subjected to pathological examination. RESULTS: Nineteen patients were enrolled in this study including 15 males and 4 females with an average age of 55 years old. Of the enrollees, 8 patients (42.1%) were successfully diagnosed with samples obtained through TBNA, including 6 cases of lung cancer, 1 case of non-specific inflammation, and 1 case of cryptococcal infection. The diagnostic rate was 42.1%. No post-procedural complications were observed among the patients. There was no significant difference in nodule diameter between patients with a diagnostic sample and those in whom TBNA failed to provide a diagnosis (2.99±0.96 vs. 2.26±1.27 cm, P=0.20). CONCLUSIONS: With the assistance of REBUS, TBNA can acquire sufficient samples to achieve a reasonably diagnostic rate for parenchymal lung lesions located near the inner field of lung on the CT image without intrabronchial invasion.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

Power law behaviour in the saturation regime of fatality curves of the COVID-19 pandemic.

We apply a versatile growth model, whose growth rate is given by a generalised beta distribution, to describe the complex behaviour of the fatality curves of the COVID-19 disease for several countries in Europe and North America. We show that the COVID-19 epidemic curves not only may present a subexponential early growth but can also exhibit a similar subexponential (power-law) behaviour in the saturation regime. We argue that the power-law exponent of the latter regime, which measures how quickly the curve approaches the plateau, is directly related to control measures, in the sense that the less strict the control, the smaller the exponent and hence the slower the diseases progresses to its end. The power-law saturation uncovered here is an important result, because it signals to policymakers and health authorities that it is important to keep control measures for as long as possible, so as to avoid a slow, power-law ending of the disease. The slower the approach to the plateau, the longer the virus lingers on in the population, and the greater not only the final death toll but also the risk of a resurgence of infections.

The utility of endobronchial ultrasound-transbronchial needle aspiration in patients with suspected extra-pulmonary sarcoidosis without thoracic lymphadenopathy.

BACKGROUND: Diagnosis of extra-pulmonary sarcoidosis can be difficult, and a biopsy is usually required. We evaluated the utility of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) in patients with suspected extra-pulmonary sarcoidosis with thoracic lymph nodes ≤10 mm on chest computed tomography (CT) and no or minimal pulmonary infiltrates. METHODS: The Cleveland Clinic bronchoscopy registry was screened. Patients with thoracic lymph nodes >10 mm on short axis or significant pulmonary infiltrates in the chest CT scan were excluded. Two separate analyses using expert consensus (before and after release of bronchoscopy results) were the reference standard. RESULTS: 15 patients met the inclusion criteria. 40% had suspected ocular, 33% cardiac and 27% neurologic sarcoidosis. Six patients (40%) had EBUS-TBNA compatible with sarcoidosis. When the reference standard was the consensus diagnosis blinded to bronchoscopy results, the sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA were 56%, 83%, 83%, and 56% respectively. The combination of a positive EBUS-TBNA and BAL CD4/CD8 improved the specificity from 83 to 100%, but the difference was not statistically significant (p = 0.074). When the reference standard was the consensus diagnosis with the bronchoscopic results, the sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA were 75%, 100%, 100%, and 78% respectively. CONCLUSIONS: In patients with suspected extra-pulmonary sarcoidosis, the EBUS-TBNA may be useful in the diagnosis of patients with thoracic lymph nodes ≤10 mm and no or minimal pulmonary infiltrates on chest CT. Larger and prospective studies are needed to validate our findings.

AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.

BACKGROUND: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management. METHODS: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique. RESULTS: A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations. CONCLUSION: This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.

Continuous infusion chemotherapy, radiotherapy, and FDG-PET are feasible during extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) may be used in extreme circumstances for patients with a mediastinal mass and respiratory failure. We report on a young man with primary mediastinal B-cell lymphoma invading into the trachea, requiring a 40-day ECMO run who underwent fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and treatment with concurrent mediastinal irradiation and continuous infusion chemotherapy while on this life-saving technology. This case illustrates that oncology patients may be managed by multidisciplinary teams for extended periods in extraordinary circumstances using multimodality therapies. Additionally, to our knowledge this is the first case to demonstrate the feasibility of FDG-PET imaging while on ECMO.

Modelling fatality curves of COVID-19 and the effectiveness of intervention strategies.

The main objective of the present article is twofold: first, to model the fatality curves of the COVID-19 disease, as represented by the cumulative number of deaths as a function of time; and second, to use the corresponding mathematical model to study the effectiveness of possible intervention strategies. We applied the Richards growth model (RGM) to the COVID-19 fatality curves from several countries, where we used the data from the Johns Hopkins University database up to May 8, 2020. Countries selected for analysis with the RGM were China, France, Germany, Iran, Italy, South Korea, and Spain. The RGM was shown to describe very well the fatality curves of China, which is in a late stage of the COVID-19 outbreak, as well as of the other above countries, which supposedly are in the middle or towards the end of the outbreak at the time of this writing. We also analysed the case of Brazil, which is in an initial sub-exponential growth regime, and so we used the generalised growth model which is more appropriate for such cases. An analytic formula for the efficiency of intervention strategies within the context of the RGM is derived. Our findings show that there is only a narrow window of opportunity, after the onset of the epidemic, during which effective countermeasures can be taken. We applied our intervention model to the COVID-19 fatality curve of Italy of the outbreak to illustrate the effect of several possible interventions.

Complications following symptom-limited thoracentesis using suction.

BACKGROUND: Thoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO. METHODS: A retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included. RESULTS: Pleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04-0.54%; 95% CI 0.13-2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01). CONCLUSIONS: Symptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

Convex probe endobronchial ultrasound: historical, contemporary, and cutting-edge applications.

The use of convex-probe endobronchial ultrasound (CP-EBUS) has revolutionized bronchoscopy. It has provided the option of a relatively safe, minimally invasive approach for the assessment of various intrathoracic diseases. In current practice, its most dramatic impact has been on the diagnosing and staging of lung cancer. It has served as an invaluable tool that has replaced mediastinoscopy in a variety of clinical scenarios. Many pulmonologists and thoracic surgeons consider CP-EBUS the most significant milestone in bronchoscopy after the development of the flexible bronchoscope itself. In this review, we summarize the historical aspects, current indications, technical approach, and future direction of CP-EBUS.

Idiopathic subglottic stenosis: a review.

Idiopathic subglottic stenosis (iSGS) is a fibrotic disease of unclear etiology that produces obstruction of the central airway in the anatomic region under the glottis. The diagnosis of this entity is difficult, usually delayed and confounded with other common respiratory diseases. No apparent etiology is identified even after a comprehensive workup that includes a complete history, physical examination, pulmonary function testing, auto-antibodies, imaging studies, and endoscopic procedures. This approach, however, helps to exclude other conditions such as granulomatosis with polyangiitis (GPA). It is also helpful to characterize the lesion and outline management strategies. Therapeutic endoscopic procedures and surgery are the most common management modalities, but medical therapy can also play a significant role in preventing or delaying recurrence. In this review, we describe the morphology, pathophysiology, clinical presentation, evaluation, management, and prognosis of iSGS.