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Endotracheal aspirates (ETAs) are widely used for microbiologic studies of the respiratory tract in intubated patients. However, they involve sampling through an established endotracheal tube using suction catheters, both of which can acquire biofilms that may confound results. Does standard clinical ETA in intubated patients accurately reflect the authentic lower airway bacterial microbiome? Comprehensive quantitative bacterial profiling using 16S rRNA V1-V2 gene sequencing was applied to compare bacterial populations captured by standard clinical ETA vs contemporaneous gold standard samples acquired directly from the lower airways through a freshly placed sterile tracheostomy tube. The study included 13 patients undergoing percutaneous tracheostomy following prolonged (median, 15 days) intubation. Metrics of bacterial composition, diversity, and relative quantification were applied to samples. Pre-tracheostomy ETAs closely resembled the gold standard immediate post-tracheostomy airway microbiomes in bacterial composition and community features of diversity and quantification. Endotracheal tube and suction catheter biofilms also resembled cognate ETA and fresh tracheostomy communities. Unbiased molecular profiling shows that standard clinical ETA sampling has good concordance with the authentic lower airway microbiome in intubated patients. [ABSTRACT FROM AUTHOR]

Rationale: Outcomes of interventional lymphangiographic treatment of nontraumatic chylous pleural effusions using traditional approaches have been highly variable. Recent advances in lymphatic imaging have revealed variations in underlying pathophysiology, enabling improved targeting of therapeutic interventions. Objectives: To assess outcomes of an algorithm for management of nontraumatic chylous pleural effusions based on advanced magnetic resonance (MR) identification of various abnormalities in the thoracoabdominal lymphatic network that give rise to chylothorax. Methods: Novel lymphatic MR imaging was performed in 52 patients aged 11-89 years. Three distinct pathophysiological patterns were found: 1) abnormal pulmonary lymphatic flow from the thoracic duct only; 2) abnormal pulmonary lymphatic flow from retroperitoneal lymphatic networks with or without involvement of the thoracic duct; and 3) chylous ascites presenting as chylous pleural effusion. Lymphatic interventions were individualized to the underlying pathophysiological patterns. Results: In 41/52 (79%) patients, imaging revealed abnormal pulmonary lymphatic flow from the thoracic duct and/or retroperitoneal lymphatic networks. Thoracic duct embolization and/or interstitial embolization of retroperitoneal lymphatic resulted in resolution of chylothorax in this group in 38/41 (93%) of those patients. Five patients experienced grade 1 or 2 complications. One patient succumbed to postoperative stress-induced cardiomyopathy and pulmonary embolism. Chylous ascites was the cause of chylothorax in 11/52 (21%) patients. Eight chose to undergo interventions for chylous ascites with clinical success in 6/8 (75%). Conclusions: Application of magnetic resonance imaging-guided intervention algorithm resulted in successful control of nontraumatic chylothorax in 93% patients with abnormal pulmonary lymphatic flow. Appropriate treatment of chylous ascites presenting as a pleural effusion requires systematic evaluation and diagnosis prior to potential treatments. [ABSTRACT FROM AUTHOR]

Introduction: Patients with COVID-19 ARDS require significant amounts of sedation and analgesic medications which can lead to longer hospital/ICU length of stay, delirium, and has been associated with increased mortality. Tracheostomy has been shown to decrease the amount of sedative, anxiolytic and analgesic medications given to patients. The goal of this study was to assess whether tracheostomy decreased sedation and analgesic medication usage, improved markers of activity level and cognitive function, and clinical outcomes in patients with COVID-19 ARDS. Study Design and Methods: A retrospective registry of patients with COVID-19 ARDS who underwent tracheostomy creation at the University of Pennsylvania Health System or the Johns Hopkins Hospital from 3/2020 to 12/2020. Patients were grouped into the early (≤14 days, n=31) or late (15+days, n=97) tracheostomy groups and outcome data collected. Results: 128 patients had tracheostomies performed at a mean of 19.4 days, with 66% performed percutaneously at bedside. Mean hourly dose of fentanyl, midazolam, and propofol were all significantly reduced 48-h after tracheostomy: fentanyl (48-h pre-tracheostomy: 94.0 mcg/h, 48-h post-tracheostomy: 64.9 mcg/h, P =.000), midazolam (1.9 mg/h pre vs. 1.2 mg/h post, P= .0012), and propofol (23.3 mcg/kg/h pre vs. 8.4 mcg/kg/h post, P =.0121). There was a significant improvement in mobility score and Glasgow Coma Scale in the 48-h pre- and post-tracheostomy. Comparing the early and late groups, the mean fentanyl dose in the 48-h pre-tracheostomy was significantly higher in the late group than the early group (116.1 mcg/h vs. 35.6 mcg/h, P = .03). ICU length of stay was also shorter in the early group (37.0 vs. 46.2 days, P =.012). Interpretation: This data supports a reduction in sedative and analgesic medications administered and improvement in cognitive and physical activity in the 48-h period post-tracheostomy in COVID-19 ARDS. Further, early tracheostomy may lead to significant reductions in intravenous opiate medication administration, and ICU LOS. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 50-year-old male suffering with sarcoidosis complicated by interstitial lung disease and cirrhosis underwent combined liver and bilateral lung transplantation. Post transplant he developed severe ischemic airway changes notable for sloughing and necrosis beyond the anastomoses.

Coronavirus disease 2019 (COVID-19) has had a devastating impact around the world. With high rates of transmission and no curative therapies or vaccine yet available, the current cornerstone of management focuses on prevention by social distancing. This includes decreased health care contact for patients. Patients with lung cancer are a particularly vulnerable population, where the risk of mortality from cancer must now be balanced by the potential risk of a life-threatening infection. In these unprecedented times, a collaborative and multidisciplinary approach is required to streamline but not compromise care. We have developed guidelines at our academic cancer center to standardize management of patients with lung cancer across our health care system and provide guidance to the larger oncology community. We recommend that general principles of lung cancer treatment continue to be followed in most cases where delays could result in rapid cancer progression. We recognize that our recommendations may change over time based on clinical resources and the evolving nature of the COVID-19 pandemic. In principle, however, treatment paradigms must continue to be individualized, with careful consideration of risks and benefits of continuing or altering lung cancer–directed therapy. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma. [ABSTRACT FROM AUTHOR]

Endobronchial stents are increasingly used to treat airway complications in multiple conditions including lung transplantation but little is known about the biofilms that form on these devices. We applied deep sequencing to profile luminal biofilms of 46 endobronchial stents removed from 20 subjects primarily with lung transplantation-associated airway compromise. Microbial communities were analyzed by bacterial 16S rRNA and fungal ITS marker gene sequencing. Corynebacterium was the most common bacterial taxa across biofilm communities. Clustering analysis revealed three bacterial biofilm types: one low diversity and dominated by Corynebacterium; another was polymicrobial and characterized by Staphylococcus; and the third was polymicrobial and associated with Pseudomonas, Streptococcus, and Prevotella. Biofilm type was significantly correlated with stent material: covered metal with the Staphylococcus-type biofilm, silicone with the Corynebacterium-dominated biofilm, and uncovered metal with the polymicrobial biofilm. Subjects with sequential stents had frequent transitions between community types. Fungal analysis found Candida was most prevalent, Aspergillus was common and highly enriched in two of three stents associated with airway anastomotic dehiscence, and fungal taxa not typically considered pathogens were highly enriched in some stents. Thus, molecular analysis revealed a complex and dynamic endobronchial stent biofilm with three bacterial types that associate with stent material, a central role for Corynebacterium, and that both expected and unexpected fungi inhabit this unique niche. The current work provides a foundation for studies to investigate the relationship between stent biofilm composition and clinical outcomes, mechanisms of biofilm establishment, and strategies for improved stent technology and use in airway compromise. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has now become a recognized approach to treating cancers. In addition to checkpoint blockade, adoptive T cell transfer (ACT) using chimeric antigen receptors (CARs) has shown impressive clinical outcomes in leukemias and is now being explored in solid tumors. CARs are engineered receptors, stably or transiently transduced into T cells, that aim to enhance T cell effector function by recognizing and binding to a specific tumor-associated antigen. In this review, we provide a summary of CAR T cell preclinical studies and clinical trials for malignant pleural mesothelioma (MPM), a rare, locally invasive pleural cancer with poor prognosis. We list other attractive potential targets for CAR T cell therapy for MPM, and discuss augmentation strategies of CAR T cell therapy with other forms of immunotherapy in this disease. [ABSTRACT FROM AUTHOR]

Rationale: Transbronchial cryobiopsy is an emerging technique for obtaining biopsies of lung parenchyma. Despite limited evidence of its safety and efficacy in direct comparison with other available biopsy procedures, pulmonologists are integrating this technique into clinical practice with the hope of avoiding the risks of surgical lung biopsy.Objectives: To report the rate of severe complications and diagnostic outcomes immediately after introduction of transbronchial cryobiopsy into the clinical practice of a single-center, high-volume, interventional pulmonary group at a large academic medical center in the United States.Methods: We conducted a retrospective review of a case series.Results: Twenty-five consecutive patients underwent transbronchial cryobiopsy for a variety of indications over a period of 14 weeks. In the absence of a strict protocol, a variety of techniques were employed by four attending interventional pulmonologists and one advanced interventional pulmonology fellow to plan and complete the procedures. Three patients (12%) experienced serious hemorrhage immediately after biopsy, including one patient who survived a life-threatening bleed. Two procedures were complicated by an iatrogenic pneumothorax. One patient experienced hypercapnic respiratory failure shortly after the procedure. A definitive diagnosis was made with 14 cryobiopsies (56%). Another five biopsies (20%) contributed to a presumptive diagnosis achieved by multidisciplinary consensus.Conclusions: Transbronchial cryobiopsy may have diagnostic and safety limitations that are not yet well appreciated, given the state of the published medical literature. Major questions remain regarding the safest procedural protocol to be used when performing transbronchial cryobiopsy. Thorough planning and a high degree of caution are encouraged on first introduction of this technique into a clinical practice. [ABSTRACT FROM AUTHOR]

Cryotherapy is an evolving therapeutic and diagnostic tool used during bronchoscopy. Through rapid freeze-thaw cycles, cryotherapy causes cell death and tissue necrosis or tissue adherence that can be used via the flexible or rigid bronchoscope. This extreme cold can be used through the working channel of the bronchoscope via a specialized cryoprobe or directly with the use of spray cryotherapy. These properties allow for multiple bronchoscopic techniques, each with its own equipment and procedural, safety, and efficacy considerations. Bronchoscopic cryotherapy can be used in a variety of clinical scenarios, including the treatment of malignant and benign central airway obstruction and low-grade airway malignancy, foreign body removal or cryoextraction, endobronchial biopsy, and transbronchial biopsy. The bulk of the experience with bronchoscopic cryotherapy consists of uncontrolled case series of malignant central airway obstruction. There are also controlled data supporting the use of cryoadhesion for endobronchial biopsies, albeit with an increased risk of controllable bleeding. The use of cryoadhesion for transbronchial biopsies is an active area of investigation with limited controlled data. In addition, there are promising future directions using bronchoscopic cryotherapy, including chemosensitizing malignancy with cryotherapy and capitalizing on the synergy between cryotherapy and radiation. [ABSTRACT FROM AUTHOR]

The article presents a brief review on the advances in pleural effusion management approaches in the U.S. and presents updated changes to common procedural terminology (CPT) billing codes in the wake of technological advances in pleural disease management approaches. Topics include the emerging tools in improving noninvasive pleural disease evaluation and procedures and the separate CPT codes for newer techniques such as imaging and percutaneous approaches.

BACKGROUND: Anesthesia for bronchoscopy presents unique challenges, as constant stimulus due to bronchoscope needs to be obtunded using drugs with a minimal post-procedure residual effect. Remifentanil for maintenance is an ideal choice, but optimal doses are yet to be determined. MATERIALS AND METHODS: Bronchoscopic procedures were prospectively evaluated for 4 months studying the frequency of complications and anesthesia techniques. Anesthesia was maintained on remifentanil/propofol infusion avoiding neuromuscular blockers. Laryngeal mask airway was used for the controlled ventilation (with high oxygen concentration) that also served as a conduit for bronchoscope insertions. Anesthesiologists were blinded to the study (avoiding performance bias) and the Pulmonologist was blinded to the anesthesia technique (to document unbiased procedural satisfaction scores). Procedures were divided into 2 groups based on the dose of remifentanil used for maintenance: Group-H (high dose −0.26 to 0.5 μg/kg/min and Group-NH (non-high dose ≤0.25 μg/kg/min). RESULTS: Observed 75 procedures were divided into Group-H (42) and Group-NH (33). Number of statistical difference was found in demography, procedural profile, hemodynamic parameters and total phenylephrine used. Chi-square test showed Group-NH had significantly higher frequency of laryngospasm (P = 0.047) and coughing (P = 0.002). The likelihood ratio of patient coughing and developing laryngospasm in Group-NH was found to be 4.56 and 10.97 times respectively. Minimum pulse-oximeter saturation was statistically higher in Group-H (98.80% vs. 96.50% P = 0.009). Pulmonologist satisfaction scores were significantly better in Group-H. CONCLUSIONS: High dose of remifentanil infusion is associated with a lower incidence of coughing and laryngospasms during bronchoscopy. Simultaneously, it improves Pulmonologist's satisfaction and procedural conditions. [ABSTRACT FROM AUTHOR]

The article discusses the proposed Current Procedural Terminology code which reflects work performed during stereotactic body radiation therapy (SBRT) by consulting specialists and subspecialists. It cites the increasing use of SBRT in treating patients with stage I non-small cell lung cancer (NSCLC). Particular focus is given to the clinical outcomes, toxicity profiles and treatment delivery for SBRT.

Pleural malignancies, either primary or metastatic, are common and problematic clinical issues in thoracic oncology and pulmonary medicine. Malignant pleural mesothelioma and metastatic pleural effusions often present late in the course of a disease and have a dramatic impact on the patient's quality of life and survival. Novel approaches to manage mesothelioma and malignant pleural effusions are desperately needed and the pleural space provides a unique platform as an easily accessible body cavity for developing and assessing these treatments and their responses. In this review, we discuss the unique intrapleural chemotherapeutic, immunotherapeutic and genetic treatments that have been investigated, as well as those under current clinical development. While responses have been demonstrated to variable degrees with all these approaches, an integrated multimodality approach incorporating these methods with other anti-neoplastic interventions ultimately will ensure the best responses and patient outcomes. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans. [ABSTRACT FROM AUTHOR]

This study evaluates two different techniques for topically anaesthetizing the airway with lidocaine during curvilinear probe endobronchial ultrasound bronchoscopy (CP-EBUS): standard injection through the working channel and spray catheter application. This was a randomized, non-blinded, single-centre pilot study. Patients with plans for CP-EBUS under moderate sedation were enrolled. All patients received nebulized lidocaine followed by posterior oropharyngeal lidocaine via atomizer and a cotton ball swab using McGill forceps. Patients were then randomly assigned to lidocaine administration using spray catheter instillation or direct application through the working channel. Lidocaine was administered in a uniform fashion by a single investigator throughout the study. The primary end-point was the number of significant coughing episodes in the first 30 min of bronchoscopy. Other end-points included lidocaine and intravenous sedation medication dosage; severe coughing session; and number of transbronchial needle aspirations. Forty patients were included in the study: 20 patients in each group. The median numbers of coughing episodes in the first 30 min were 1 (spray catheter group) and 2 (standard injection group) ( P < 0.004). Six patients in the standard installation group experienced severe coughing sessions, while there was none in the spray catheter group ( P = 0.02). There were no statistical differences between the groups in the dosage of lidocaine or intravenous sedation medications used. There were a greater number of transbronchial needle aspirations performed in the spray catheter group ( P = 0.008). Lidocaine delivery via the spray catheter reduced the number of significant coughing episodes compared with standard working channel injection during CP-EBUS. Larger studies are needed to confirm these exploratory findings. We compared two techniques for anaesthetizing the airway during curvilinear endobronchial ultrasound bronchoscopy: lidocaine injection through the working channel and spray catheter aerosolization. A prospective randomized study was performed under moderate sedation with coughing as the primary end-point. This study offers an additional insight to optimize bronchoscopy under moderate sedation. [ABSTRACT FROM AUTHOR]

In the current era of organ shortages and long wait times for life-saving transplants, marginal or extended donors are increasingly being considered; one such category of marginal organs is from donors with a previous history of malignancy. Melanoma in particular has been associated with increased risk of developing late recurrence. In this report, we describe a case of fatal donor melanoma transmission to a 64-year-old lung transplant recipient 32 years after surgical excision of the melanoma. Based on this report and review of the available literature, we conclude that a history of donor melanoma, regardless of the stage and time interval from ‘curative’ surgical resection, should remain a strong relative contraindication to transplantation. [ABSTRACT FROM AUTHOR]

The article provides Malignant Pleural Effusions (MPE) management strategies. MPE is a complication of advanced malignancies, with lung and breast cancer accounting for most of it. There are several approaches to MPE management, with each procedure to drain the pleural space and to relieve respiratory syndromes including repeat thoracentesis, placement of an indwelling cuffed and medical pleuroscopy.

Advanced-stage malignancies are often characterized by systemic complications related to primary tumor progression. Pulmonary complications such as cough and dyspnea are relatively common and can dramatically reduce quality of life and lead to inpatient or intensive care unit admission. Although cancer-induced cough can be improved with radiation therapy or chemotherapy, or both, it is often best managed with central-acting opioids. Dyspnea can arise from a range of etiologies that may or may not be related to the underlying malignant pulmonary disease. Recent advances in the management of malignant pleural effusion, central airway obstruction, and superior vena cava syndrome have allowed relatively noninvasive interventions to be performed that can significantly reduce dyspnea, minimize inpatient hospitalization, and improve the quality of life in patients where the major focus is palliative care. [ABSTRACT FROM AUTHOR]

The appropriate and timely evaluation and treatment of patients with severely elevated blood pressure is essential to avoid serious adverse outcomes. Most importantly, the distinction between a hypertensive emergency (crisis) and urgency needs to be made. A sudden elevation in systolic (SBP) and/or diastolic blood pressure (DBP) that is associated with acute end organ damage (cardiovascular, cerebrovascular, or renal) is defined as a hypertensive crisis or emergency. In contrast, acute elevation in SBP and/or DBP not associated with evidence of end organ damage is defined as hypertensive urgency. In patients with a hypertensive emergency, blood pressure control should be attained as expeditiously as possible with parenteral medications to prevent ongoing and potentially permanent end organ damage. In contrast, with hypertensive urgency, blood pressure control can be achieved with the use of oral medications within 24–48 hours. This paper reviews the management of hypertensive emergencies. [ABSTRACT FROM AUTHOR]