Acute hypoxic respiratory failure due to Lenalidomide-induced interstitial pneumonitis in a patient with multiple myeloma.

BACKGROUND: Patients with multiple myeloma are immunosuppressed due to both the disease itself and immunosuppressive therapies. Thus, when presenting with respiratory failure and pulmonary opacities, pneumonia must be considered. However, while rare, immunomodulating medications used in the treatment of multiple myeloma can also cause potentially life-threatening respiratory failure, a distinction which has important treatment implications. CASE PRESENTATION: An 80-year-old male with recently diagnosed multiple myeloma undergoing treatment with lenalidomide and daratumumab presented with acute, rapidly progressive hypoxic respiratory failure ultimately requiring intubation and mechanical ventilatory support. Imaging revealed bilateral pulmonary opacities, however infectious workup was negative, and he was ultimately diagnosed with lenalidomide-induced interstitial pneumonitis, a rare but serious adverse effect of this medication. He was treated with drug discontinuation and methylprednisolone, and quickly recovered. CONCLUSION: Lenalidomide is an immunomodulating medication used in the treatment of multiple myeloma, and is associated with rare but serious cases of drug-induced interstitial pneumonitis. Thus, if a patient receiving lenalidomide develops shortness of breath and/or hypoxia, drug-induced pneumonitis must be on the differential. Permanent drug discontinuation with or without corticosteroids is the mainstay of treatment, and patients are often able to fully recover, underscoring the need for early recognition of this condition.

Interstitial lung disease progression after genomic usual interstitial pneumonia testing.

BACKGROUND: A genomic classifier for usual interstitial pneumonia (gUIP) has been shown to predict histological UIP with high specificity, increasing diagnostic confidence for idiopathic pulmonary fibrosis (IPF). Whether those with positive gUIP classification exhibit a progressive, IPF-like phenotype remains unknown. METHODS: A pooled, retrospective analysis of patients who underwent clinically indicated diagnostic bronchoscopy with gUIP testing at seven academic medical centres across the USA was performed. We assessed the association between gUIP classification and 18-month progression-free survival (PFS) using Cox proportional hazards regression. PFS was defined as the time from gUIP testing to death from any cause, lung transplant, ≥10% relative decline in forced vital capacity (FVC) or censoring at the time of last available FVC measure. Longitudinal change in FVC was then compared between gUIP classification groups using a joint regression model. RESULTS: Of 238 consecutive patients who underwent gUIP testing, 192 had available follow-up data and were included in the analysis, including 104 with positive gUIP classification and 88 with negative classification. In multivariable analysis, positive gUIP classification was associated with reduced PFS (hazard ratio 1.58, 95% CI 0.86-2.92; p=0.14), but this did not reach statistical significance. Mean annual change in FVC was -101.8 mL (95% CI -142.7- -60.9 mL; p<0.001) for those with positive gUIP classification and -73.2 mL (95% CI -115.2- -31.1 mL; p<0.001) for those with negative classification (difference 28.7 mL, 95% CI -83.2-25.9 mL; p=0.30). CONCLUSIONS: gUIP classification was not associated with differential rates of PFS or longitudinal FVC decline in a multicentre interstitial lung disease cohort undergoing bronchoscopy as part of the diagnostic evaluation.

Transbronchial Lung Cryobiopsy for Diffuse Parenchymal Lung Disease.

Transbronchial lung cryobiopsy (TBLC) offers a minimally invasive option for the diagnosis of diffuse parenchymal lung diseases, of which interstitial lung diseases comprise the most common diagnoses. It has a high diagnostic yield with prognostic and therapeutic implications. TBLC has a favorable safety profile compared with surgical lung biopsy, but associated complications include pneumothorax and bleeding. However, TBLC techniques remain variable. Here we review the latest techniques described to maximize diagnostic yield and mitigate complications of TBLC as well as how this modality has been incorporated into guidelines.

Novel Robotic-Assisted Cryobiopsy for Peripheral Pulmonary Lesions.

PURPOSE: Tissue acquisition in lung cancer is vital for multiple reasons. Primary reasons reported for molecular testing failure in lung cancer biopsy specimens include insufficient amount of tumor cells provided and inadequate tissue quality. Robotic bronchoscopy is a new tool enabling peripheral pulmonary lesion sampling; however, diagnostic yield remains imperfect possibly due to the location of nodules adjacent to or outside of the airway. The 1.1-mm cryoprobe is a novel diagnostic tool and accesses tissue in a 360-degree manner, thus potentially sampling eccentric/adjacent lesions. This study examines the diagnostic yield of the cryoprobe compared to standard needle aspiration and forceps biopsy. It additionally evaluates yield for molecular markers in cases of lung cancer. METHODS: This is a retrospective analysis of 112 patients with 120 peripheral pulmonary lesions biopsied via robotic bronchoscopy using needle aspirate, forceps, and cryobiopsy. RESULTS: The overall diagnostic yield was 90%. Nearly 18% of diagnoses were made exclusively from the cryobiopsy sample. Molecular analysis was adequate on all cryobiopsy samples sent. Digital imaging software confirmed an increase in quantity and quality of samples taken via cryobiopsy compared to needle aspirate and traditional forceps biopsy. CONCLUSION: Using the 1.1-mm cryoprobe to biopsy PPN combined with the Ion robotic bronchoscopy system is safe, feasible, and provides more diagnostic tissue than needle aspirates or traditional forceps biopsies. The combination of cryobiopsy with robotic-assisted bronchoscopy increased diagnostic yield, likely due to its 360-degree tissue acquisition which is beneficial when targeting extraluminal lesions adjacent to the airway.

Percepta Genomic Sequencing Classifier and decision-making in patients with high-risk lung nodules: a decision impact study.

BACKGROUND: Incidental and screening-identified lung nodules are common, and a bronchoscopic evaluation is frequently nondiagnostic. The Percepta Genomic Sequencing Classifier (GSC) is a genomic classifier developed in current and former smokers which can be used for further risk stratification in these patients. Percepta GSC has the capability of up-classifying patients with a pre-bronchoscopy risk that is high (> 60%) to "very high risk" with a positive predictive value of 91.5%. This prospective, randomized decision impact survey was designed to test the hypothesis that an up-classification of risk of malignancy from high to very high will increase the rate of referral for surgical or ablative therapy without additional intervening procedures while increasing physician confidence. METHODS: Data were collected from 37 cases from the Percepta GSC validation cohort in which the pre-bronchoscopy risk of malignancy was high (> 60%), the bronchoscopy was nondiagnostic, and the patient was up-classified to very high risk by Percepta GSC. The cases were randomly presented to U.S pulmonologists in three formats: a pre-post cohort where each case is presented initially without and then with a GSG result, and two independent cohorts where each case is presented either with or without with a GSC result. Physicians were surveyed with respect to subsequent management steps and confidence in that decision. RESULTS: One hundred and one survey takers provided a total of 1341 evaluations of the 37 patient cases across the three different cohorts. The rate of recommendation for surgical resection was significantly higher in the independent cohort with a GSC result compared to the independent cohort without a GSC result (45% vs. 17%, p < 0.001) In the pre-post cross-over cohort, the rate increased from 17 to 56% (p < 0.001) following the review of the GSC result. A GSC up-classification from high to very high risk of malignancy increased Pulmonologists' confidence in decision-making following a nondiagnostic bronchoscopy. CONCLUSIONS: Use of the Percepta GSC classifier will allow more patients with early lung cancer to proceed more rapidly to potentially curative therapy while decreasing unnecessary intervening diagnostic procedures following a nondiagnostic bronchoscopy.

Lung ultrasound is non-inferior to bronchoscopy for confirmation of double-lumen endotracheal tube positioning: a randomized controlled noninferiority study.

BACKGROUND: Appropriate placement of left-sided double-lumen endotracheal tubes (LDLTs) is paramount for optimal visualization of the operative field during thoracic surgeries that require single lung ventilation. Appropriate placement of LDLTs is therefore confirmed with fiberoptic bronchoscopy (FOB) rather than clinical assessment alone. Recent studies have demonstrated lung ultrasound (US) is superior to clinical assessment alone for confirming placement of LDLT, but no large trials have compared US to the gold standard of FOB. This noninferiority trial was devised to compare lung US with FOB for LDLT positioning and achievement of lung collapse for operative exposure. METHODS: This randomized, controlled, double-blind, noninferiority trial was conducted at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from October 2017 to July 2019. The study enrolled 200 ASA classification 1-3 patients that were scheduled for elective thoracic surgery requiring placement of LDLT. Study patients were randomized into either the FOB group or the lung US group after initial blind placement of LDLT. Five patients were excluded due to protocol deviation. In the FOB group (n = 98), fiberoptic bronchoscopy was used to confirm lung collapse due to proper positioning of the LDLT, and to adjust the tube if necessary. In the US group (n = 97), lung ultrasonography of four pre-specified zones (upper and lower posterior and mid-axillary) was used to assess lung collapse and guide adjustment of the tube if necessary. The primary outcome was presence of adequate lung collapse as determined by visual grading by the attending surgeon on scale from 1 to 4. Secondary outcomes included the time needed to adjust and confirm lung collapse, the time from finishing LDLT positioning to the grading of lung collapse, and intraoperative parameters such has hypotension or hypertension, hypoxia, and hypercarbia. The patient, attending anesthesiologist, and attending thoracic surgeon were all blinded to the intervention arm. RESULTS: The primary outcome of lung collapse by visual grading was similar between the intervention and the control groups, with 89 patients (91.8%) in the US group compared to 83 patients (84.1%) in the FOB group (p = 0.18) experiencing adequate collapse. This met criteria for noninferiority per protocol analysis. The median time needed to confirm and adjust LDLT position in the US group was 3 min (IQR 2-5), which was significantly shorter than the median time needed to perform the task in the FOB group (6 min, IQR 4-10) (p = 0.002). CONCLUSIONS: In selected patients undergoing thoracic surgery requiring LDLT, lung ultrasonography was noninferior to fiberoptic bronchoscopy in achieving adequate lung collapse and reaches the desired outcome in less time. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov, NCT03314519 , Principal investigator: Kasana Raksamani, Date of registration: 19/10/2017.

Combined Percutaneous Tracheostomy and Endoscopic Gastrostomy Tubes in COVID-19: A Prospective Series of Patient Outcomes.

Background: A significant number of patients with severe respiratory failure related to COVID-19 require prolonged mechanical ventilation. Minimal data exists regarding the timing, safety, and efficacy of combined bedside percutaneous tracheostomy and endoscopy gastrostomy tube placement in these patients. The safety for healthcare providers is also in question. This study's objective was to evaluate the effectiveness and safety of combined bedside tracheostomy and gastrostomy tube placement in COVID-19 patients. Design and Methods: This is a single arm, prospective cohort study in patients with COVID-19 and acute respiratory failure requiring prolonged mechanical ventilation who underwent bedside tracheostomy and percutaneous endoscopic gastrostomy placement. Detailed clinical and procedural data were collected. Descriptive statistics were employed and time to event curves were estimated and plotted using the Kaplan Meier method for clinically relevant prespecified endpoints. Results: Among 58 patients, the median total intensive care unit (ICU) length of stay was 29 days (24.7-33.3) with a median of 10 days (6.3-13.7) postprocedure. Nearly 88% of patients were weaned from mechanical ventilation postprocedure at a median of 9 days (6-12); 94% of these were decannulated. Sixty-day mortality was 10.3%. Almost 90% of patients were discharged alive from the hospital. All procedures were done at bedside with no patient transfer required out of the ICU. A median of 3.0 healthcare personnel total were present in the room per procedure. Conclusion: This study shows that survival of critically ill COVID-19 patients after tracheostomy and gastrostomy was nearly 90%. The time-to-event curves are encouraging regarding time to weaning, downsizing, decannulation, and discharge. A combined procedure minimizes the risk of virus transmission to healthcare providers in addition to decreasing the number of anesthetic episodes, transfusions, and transfers patients must undergo. This approach should be considered in critically ill COVID-19 patients requiring prolonged mechanical ventilation.

Pre-Procedural COVID-19 Nasopharyngeal Swab Has Good Concordance with Bronchoalveolar Lavage in Patients at Low Risk for Viral Infection.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has drastically affected hospital and operating room (OR) workflow around the world as well as trainee education. Many institutions have instituted mandatory preoperative SARS-CoV-2 PCR nasopharyngeal swab (NS) testing in patients who are low risk for COVID-19 prior to elective cases. This method, however, is challenging as the sensitivity, specificity, and overall reliability of testing remains unclear. OBJECTIVES: The objective of this study was to assess the concordance of a negative NS in low risk preoperative patients with lower airway bronchoalveolar lavage (BAL) specimens obtained from the same patients. METHODS: We prospectively sent intraoperative lower airway BAL samples collected within 48 h of a negative mandatory preoperative NS for SARS-CoV-2 PCR testing. All adult patients undergoing a scheduled bronchoscopic procedure for any reason were enrolled, including elective and nonelective cases. RESULTS: One-hundred eighty-nine patients were included. All BAL specimens were negative for SARS-CoV-2 indicative of 100% concordance between testing modalities. CONCLUSIONS: These results are promising and suggest that preoperative nasopharyngeal SARS-CoV-2 testing provides adequate screening to rule out active COVID-19 infection prior to OR cases in a population characterized as low risk by negative symptom screening. This information can be used for both pre-procedural screening and when reintroducing trainees into the workforce.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

Molecular Testing on Pleural Fluid Samples.

Pleural effusions are a common manifestation of both malignant and nonmalignant diseases. The sampling of pleural fluid helps categorize effusions as transudative or exudative and helps differentiate paramalignant from malignant disease. Accurate pleural fluid analysis is critical to the appropriate staging of cancers with significant prognostic and treatment implications. However, the etiology of pleural effusions remains unclear in a significant number of cases after routine thoracentesis and pleural fluid analysis. For malignant pleural effusions, cytologic evaluation of pleural fluid has a relatively low sensitivity. We describe the evolving field of molecular pleural fluid analysis in the setting of malignant disease as an active area of investigation with both diagnostic and therapeutic implications.

Transbronchial Cryobiopsies.

Transbronchial lung cryobiopsy (TBLCB) is a relatively new and promising technique for the acquisition of larger amounts of higher quality lung tissue for the diagnosis of lung diseases. There is a growing body of literature describing a diagnostic yield comparable to surgical lung biopsy with a favorable safety profile. Due to its advantages TBLCB has garnered significant interest with more institutions beginning to adopt this technique. However, several questions remain including its role in the diagnostic algorithm, indications, and technique. Herein we provide a review of the available literature describing diagnostic yield, complications, and differing techniques as well as a perspective from pathology.

Resolution of a Mobile Right Atrial Thrombus Complicating Acute Pulmonary Embolism With Low-Dose Tissue Plasminogen Activator in a Patient With Recent Craniotomy.

Right heart thrombus in transit (RHTT) is a rare, severe form of venous thromboembolism that carries a high mortality rate. The optimal treatment for RHTT has not been well established. Thrombolysis is a therapeutic modality for RHTT but carries the risk of bleeding complications including intracranial hemorrhage. Low-dose thrombolysis has been shown to be effective in treating submassive pulmonary emboli without an increased risk in bleeding complications, but it has not been studied in patients with RHTT. Here, we discuss the case of a 74-year-old male with lung cancer and recent craniotomy with metastasectomy 30 days prior to admission presenting with RHTT and bilateral pulmonary emboli (PE). He was treated successfully with low-dose thrombolysis, despite his relative contraindication to thrombolytics. To our knowledge, this is the first reported case of low-dose alteplase (tissue plasminogen activator [tPA]) used to treat an in-transit PE in the setting of recent craniotomy with metastasectomy.

Management of autism in the adult intensive care unit.

Autism comprises a growing segment of the population and can be a management challenge in the intensive care unit (ICU). We present the case of a 22-year-old male with severe autism and intellectual disorder who developed respiratory failure and required a prolonged ICU course. This patient exhibited severe distress, aggression, and self-injurious behavior. Management challenges included sedation, weaning from sedation, and liberation from mechanical ventilation. Success was achieved with a multispecialty team and by tailoring the environment and interactions to the patient's known preferences. The use of dexmedetomidine to wean high-dose benzodiazepines and opiates also permitted successful liberation from mechanical ventilation.

Analyzing bronchoalveolar fluid derived small extracellular vesicles using single-vesicle SERS for non-small cell lung cancer detection.

An emerging body of research by biologists and clinicians has demonstrated the clinical application of small extracellular vesicles (sEVs, also commonly referred to as exosomes) as biomarkers for cancer detections. sEVs isolated from various body fluids such as blood, saliva, urine, and cerebrospinal fluid have been used for biomarker discoveries with highly encouraging outcomes. Among the biomarkers discovered are those responsible for multiple cancer types and immune responses. These biomarkers are recapitulated from the tumor microenvironments. Yet, despite numerous discussions of sEVs in scientific literature, sEV-based biomarkers have so far played only a minor role for cancer diagnostics in the clinical setting, notably less so than other techniques such as imaging and biopsy. In this paper, we report the results of a pilot study (n = 10 from each of the patient and the control group) using bronchoalveolar lavage fluid to determine the presence of sEVs related to non-small cell lung cancer in twenty clinical samples examined using surface enhanced Raman spectroscopy (SERS).

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

5-Bromo-2-hy-droxy-benzonitrile.

The title compound, C(7)H(4)BrNO, crystallizes with two mol-ecules in the asymmetric unit. The two molecules exhibit nearly linear C-C N nitrile bond angles of 179.1 (4) and 177.1 (4)°. In the crystal, the mol-ecules are linked into a one-dimensional hydrogen-bonded chain by inter-actions between the phenol H atom and the nitrile N atom [N⋯O = 2.805 (4) and 2.810 (4) Å].