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.

Use of a covered self-expanding metal airway stent for severe dynamic collapse within a bronchial aortic graft conduit in a post-lung transplant patient.

We present a novel case in which a self-expanding, covered metal airway stent was utilized for severe dynamic collapse within a cadaveric aortic bronchial graft conduit in a post-lung transplant recipient with thoracic situs inversus.

Clinical Presentation and Outcomes of Pregnant Women With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

BACKGROUND: Descriptions of coronavirus disease 2019 (COVID-19) have focused on the nonpregnant adult population. This study aims to describe the clinical characteristics and perinatal outcomes of COVID-19 in pregnancy. METHODS: We searched databases from December 2019 to 30 April 2020. Eligible studies reported clinical characteristics, radiological findings, and/or laboratory testing of pregnant women during infection. Data were pooled across studies using a random-effects model. RESULTS: Twenty-four studies (136 women) were included. The most common symptoms were fever (62.9%) and cough (36.8%). Laboratory findings included elevated C-reactive protein (57%) and lymphocytopenia (50%). Ground-glass opacity was the most common radiological finding (81.7%). Preterm birth rate was 37.7% and cesarean delivery rate was 76%. There was 1 maternal death. There were 2 fetal COVID-19 cases. CONCLUSIONS: The clinical picture in pregnant women with COVID-19 did not differ from the nonpregnant population; however, the rate of preterm birth and cesarean delivery are considerably higher than international averages.

The Impact of Gravity vs Suction-driven Therapeutic Thoracentesis on Pressure-related Complications: The GRAVITAS Multicenter Randomized Controlled Trial.

BACKGROUND: Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration. METHODS: This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure. RESULTS: A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, -2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P < .001). There were no serious complications. CONCLUSIONS: Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

Tracheal tumors.

PURPOSE OF REVIEW: This article provides the most recent literature and experienced guidance about diagnosis and management of tracheal tumors, including future directions. RECENT FINDINGS: Tracheal tumors are challenging to diagnose given their nonspecific and late-onset symptoms. Critical airway obstruction is the most feared complication. The cornerstone in management of them is surgical resection whenever is possible. Different diagnostic tests (i.e., imaging and bronchoscopy) help in the assessment of resectability. Alternative management including interventional bronchoscopic techniques can be offered to patients who are not suitable for surgical resection. Radiation and chemotherapy can also be used as adjuvant, neoadjuvant or sole treatment in malignant tumors. Recent advances in tracheal transplantation and bioengineering with tracheal reconstruction have shown a new direction in the management of these tumors. All these topics will be discussed in this article. SUMMARY: Despite advances in diagnostic and therapeutic techniques, tracheal tumors are still a medical challenge. Although studies are still trying to find the best surgical techniques as well as the role for chemotherapy and radiation, most recent studies are addressing tracheal reconstruction and transplantation as the new horizon for management.

A Design-Based Stereologic Method to Quantify the Tissue Changes Associated with a Novel Drug-Eluting Tracheobronchial Stent.

BACKGROUND: Granulation tissue is a common complication of airway stenting, but no published methods can quantify the volume and type of tissue that develops. OBJECTIVE: To use design-based stereology to quantify changes in tissue volume and type associated with airway stenting. METHODS: We compared drug-eluting stents (DES) filled with gendine to standard silicone stents in pigs in an assessor-blinded randomized trial. Tracheal stents were placed via rigid bronchoscopy. After 1 month, animals were euthanized and necropsies were performed. Antimicrobial effects of the DES were assessed in trachea tissue samples, on the DES surface, and with residual gel from the DES reservoir. Tracheal thickness was measured using orthogonal intercepts. Design-based stereology was used to quantify the volume density of tissues using a point-counting method. The volume of each tissue was normalized to cartilage volume, which is unaffected by stenting. RESULTS: Pigs were randomized to DES (n = 36) or control stents (n = 9). The drug was successfully eluted from the DES, and the stent surface showed antibacterial activity. DES and controls did not differ in tissue microbiology, tracheal thickness, or granulation tissue volume. Compared to nonstented controls, stented airways demonstrated a 110% increase in soft-tissue volume (p = 0.005). Submucosal connective tissue (118%; p < 0.0001), epithelium (70%; p < 0.0001), submucosal glands (47%; p = 0.001), and smooth muscle (41%; p < 0.0001) increased in volume. CONCLUSION: Stenting doubles the volume of soft tissue in the trachea. Design-based stereology can quantify the tissue changes associated with airway stenting.

Long-term quality-adjusted survival following therapeutic bronchoscopy for malignant central airway obstruction.

BACKGROUND: While therapeutic bronchoscopy has been used to treat malignant central (CAO) airway obstruction for >25 years, there are no studies quantifying the impact of therapeutic bronchoscopy on long-term quality-adjusted survival. METHODS: We conducted a prospective observational study of consecutive patients undergoing therapeutic bronchoscopy for CAO. Patients had follow-up at 1 week and monthly thereafter until death. Outcomes included technical success (ie, relief of anatomic obstruction), dyspnoea, health-related quality of life (HRQOL) and quality-adjusted survival. RESULTS: Therapeutic bronchoscopy was performed on 102 patients with malignant CAO. Partial or complete technical success was achieved in 90% of patients. At 7 days postbronchoscopy, dyspnoea improved (mean ∆Borg-day-7=-1.8, 95% CI -2.2 to -1.3, p<0.0001) and HRQOL improved (median prebronchoscopy 0.618 utiles, 25%-75% IQR 0.569 to 0.699, mean ∆utility-day-7+0.047 utiles, 95% CI +0.023 to 0.071, p=0.0002). Improvements in dyspnoea and HRQOL were maintained long-term. Compared with the prebronchoscopy baseline, HRQOL per day of life postbronchoscopy improved (mean ∆utility-long-term+0.036 utiles, 95% CI +0.014 to 0.057, p=0.002). Median quality-adjusted survival was 109 quality-adjusted life-days (QALDs) (95% CI 74 to 201 QALDs). Factors associated with longer quality-adjusted survival included better functional status, treatment-naïve tumour, endobronchial disease, less dyspnoea, shorter time from diagnosis to bronchoscopy, absence of cardiac disease, bronchoscopic dilation and receiving chemotherapy. CONCLUSIONS: Therapeutic bronchoscopy improves HRQOL as compared with baseline, resulting in approximately a 5.8% improvement in HRQOL per day of life. The risk-benefit profile in these carefully selected patients was very favourable. TRIAL REGISTRATION NUMBER: Results; NCT03326570.

Bronchoscopic Laser Interstitial Thermal Therapy: An Experimental Study in Normal Porcine Lung Parenchyma.

BACKGROUND: Population aging and lung cancer screening strategies may lead to an increase in detection of early-stage lung cancer in medical inoperable patients. Recent advances in peripheral bronchoscopy have made it a suitable platform for ablation of small peripheral tumors. METHODS: We investigated the tissue-ablative effect of a diode laser bronchoscopically applied by a laser delivery fiber (LDF) with wide aperture on porcine lung parenchyma. Laser was tested ex vivo and in vivo to identify the most effective power settings and LDF. Chest computed tomography (CT) were obtained immediately after ablation and after 3 days of observation. At day 3, necropsy was performed. RESULTS: On the basis of our ex vivo and in vivo experiments, we selected the round-tip LDF to be activated at 25 W for 20 seconds. Ten ablations were performed in 5 pigs. One ablation resulted in a pneumothorax requiring aspiration. All animals remained stable for 72 hours. CT findings at days 1 and 3 showed an area of cavitation surrounded by consolidation and ground glass. Median size of CT findings (long axis) was 26 mm (range, 24 to 38) at day 1, and 34 mm (range, 30 to 44) at day 3. Necropsy showed an area of central char measuring from 0.8×0.7×0.9 cm to 2.4×3.5×1.2 cm, surrounded by a gray-brown to dark red area. On histology, variable degrees of necrosis were evident around the charred areas. CONCLUSION: Bronchoscopic laser interstitial thermal therapy can achieve relatively large areas of ablation of normal lung parenchyma with a low rate of periprocedural complications.

Rigid Bronchoscopy.

Rigid bronchoscopy is one of the oldest medical techniques used in the respiratory and thoracic fields. Even though its use declined after the development of flexible bronchoscopy, it has again gained importance with the growth of interventional pulmonology, becoming a critical technique taught as part of the training in this subspecialty. The therapeutic advantages compared to other approaches of thoracic pathologies makes rigid bronchoscopy a primary component in the present and future of interventional pulmonary medicine.

Advances in the management of malignant pleural effusion.

PURPOSE OF REVIEW: The current review describes the latest evidence in the management of malignant pleural effusions (MPE). RECENT FINDINGS: Daily drainage of indwelling pleural catheters achieved auto-pleurodesis at a higher rate compared with every-other-day drainage [0.47 vs. 0.24; difference in proportion of 0.23; 95% confidence interval (CI) 0.08-0.38; P = 0.003]. In patients with MPE undergoing talc pleurodesis, a large multicenter randomized clinical trial found that pain control with opiates vs. nonsteroidal anti-inflammatory drugs (NSAID) group were not significantly different (mean visual analog scale of 23.8 vs. 22.1 mm, respectively, adjusted difference -1.5 mm; 95% CI 1.3-3.4; P = 0.40). NSAID use was found to be noninferior to opiates with respect to the rate of pleurodesis failure at 3-month follow-up (prespecified noninferiority margin 15%, failure rates 20% opiates vs. 23% NSAIDS, respectively, difference -3%, 95% CI -10% to ∞; P = 0.004 for noninferiority). Talc remains the most effective sclerosing agent based on multiple systematic reviews and meta-analyses. SUMMARY: More prospective studies are needed to determine the optimal frequency of indwelling pleural catheters drainage. NSAIDS can be used for pain control and do not adversely impact the chance of successful pleurodesis.

Recent advances in diagnostic bronchoscopy.

The field of diagnostic bronchoscopy has been revolutionized in the last decade primarily with the advent of endobronchial ultrasound (EBUS) but also with the addition of multiple different techniques for "guided-bronchoscopy". These advances have had a substantial impact in the management of lung cancer with bronchoscopy now providing both diagnosis and mediastinal staging in a single procedure. EBUS has, in fact, become the first choice for staging of the mediastinum over cervical mediastinoscopy (CM). Although EBUS is now a well-established technique, there are continuous efforts from the scientific community to improve its diagnostic performance, and these will be reviewed in this manuscript. The term "guided-bronchoscopy" was recently coined to describe a myriad of techniques that guide our bronchoscopes or bronchoscopic tools into the periphery of the lungs in addition to our conventional fluoroscopy. Electromagnetic and non-electromagnetic navigation, thin and ultrathin scopes, as well as radial-probe EBUS have collectively increased our yield for smaller peripheral lung lesions and continue to evolve. Despite this improved diagnostic yield, there is still ample room for improvement and newer techniques are under way. With new therapies available for patients with interstitial lung disease, achieving a specific histologic diagnosis is now of paramount importance. Given the high morbidity and mortality of surgical biopsies, bronchoscopic cryobiopsy is being rapidly adopted as a safer and effective alternative, and it is likely going to play a major role in the management of these diseases in the near future. This manuscript we will focus on recent advances in EBUS, guided-bronchoscopy, and the use of cryobiopsy.

Identification and characterization of catheter-related bloodstream infections due to viridans group streptococci in patients with cancer.

Viridans group streptococci (VGS), a leading cause of bloodstream infection (BSI) in cancer patients, are thought to arise from the gastrointestinal tract. We sought to determine whether central venous catheters may serve as the source of VGS BSI, and to compare the ability of the newly proposed mucosal barrier injury laboratory-confirmed BSI definition to assign a VGS BSI source compared with the catheter-related BSI definition.

The utility of proadrenomedullin and procalcitonin in comparison to C-reactive protein as predictors of sepsis and bloodstream infections in critically ill patients with cancer*.

OBJECTIVES: Infections in critically ill patients continue to impose diagnostic and therapeutic challenges. We seek to investigate the utility of proadrenomedullin and procalcitonin as diagnostic and prognostic biomarkers in febrile critically ill patients with cancer and compare their performance with that of C-reactive protein. DESIGN: Single-center prospective cohort study. SETTING: Tertiary care, academic, university hospital. PATIENTS: One hundred fourteen critically ill patients with cancer with fever. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the Kryptor technology afterward. Of the 114 adult patients, 27 had bloodstream infections, 36 had localized infections, and the remaining had no infections. The area under the receiver operating characteristic curve for bloodstream infection diagnosis was significantly greater for proadrenomedullin (0.70; 95% CI, 0.59-0.82) and procalcitonin (0.71; 95% CI, 0.60-0.83) compared with C-reactive protein (0.53; 95% CI, 0.39-0.66) (p = 0.021 and p = 0.003, respectively). Receiver operating characteristic analysis also showed that proadrenomedullin (p = 0.005) and procalcitonin (p = 0.009) each had a better performance than C-reactive protein in predicting patients' mortality within 2 months after their fever onset. Regarding patients' response to antimicrobial therapy, proadrenomedullin, procalcitonin, and C-reactive protein levels all significantly decreased from baseline to follow-up in responders (p ≤ 0.002), whereas only proadrenomedullin level significantly increased in nonresponders (p < 0.0001). In patients with documented infections, proadrenomedullin (0.81; 95% CI, 0.71-0.92) and procalcitonin (0.73; 95% CI, 0.60-0.85) each had a greater area under the curve compared with C-reactive protein (0.59; 95% CI, 0.45-0.73) as for as predicting response (p = 0.004 and p = 0.043, respectively). However, for all febrile patients, proadrenomedullin had a significantly greater area under the curve for predicting favorable response than procalcitonin (p < 0.0001). CONCLUSION: In critically ill patients with cancer, proadrenomedullin and procalcitonin both have a promising role in predicting bloodstream infections in a manner more helpful than C-reactive protein. These two biomarkers were superior to C-reactive protein in the prognostic analysis of response to antimicrobial therapy for those patients with documented infections. However, proadrenomedullin was superior to procalcitonin in predicting response in all febrile patients and was unique in showing increased levels among nonresponders.

Pro-adrenomedullin as a novel biomarker for predicting infections and response to antimicrobials in febrile patients with hematologic malignancies.

BACKGROUND: Health professionals and researchers have become increasingly interested in biomarkers that help them in diagnosis of infections with recent growing attention to procalcitonin (PCT) and pro-adrenomedullin (proADM). METHODS: This study compares proADM to PCT as diagnostic and prognostic biomarkers of infection in febrile patients with hematologic malignancies (HMs). From June 2009 to December 2010, 340 febrile HM patients were evaluated for presence of sepsis, systemic inflammatory response syndrome (SIRS), documented infections, and response to antimicrobial therapy. RESULTS: ProADM and PCT levels were measured at onset of fever and then on days 4-7 afterward. Of the 340 patients, 103 had definite sepsis, and 159 had SIRS. Only proADM initial levels were significantly higher in patients with localized bacterial infections than in those with no documented infection (P = .019) and in patients with definite sepsis than those with SIRS (P = .023). The initial proADM and PCT levels were significantly higher in neutropenic patients with BSIs than in those without documented infections (P = .010 and P = . 011, respectively). Follow-up, proADM, and PCT levels decreased significantly in response to antimicrobial therapy in patients with bacterial infections (BSIs or localized; P = .007 and P = .002, respectively). CONCLUSIONS: ProADM and PCT have promising roles in assisting clinicians in managing febrile HM patients. However, proADM appears to have the advantage of predicting localized bacterial infection and differentiating sepsis from SIRS.

Palatal mucormycosis in patients with hematologic malignancy and stem cell transplantation.

We present two patients with acute myelogenous leukemia who developed palatal mucormycosis, as well as a review of 15 well described reported cases of the same condition in patients who had hematologic malignancy and had undergone hematopoietic stem cell transplantation. Early diagnosis of palatal mucormycosis requires high suspicion of the disease along with a thorough oral examination. Mucormycosis is a devastating disease with a high mortality rate, thereby stressing the importance for early appropriate antifungal therapy in immunocompromised patients with palatal lesions while awaiting the results of histopathology and cultures.