Accuracy of Cytologic vs Histologic Specimens for Assessment of Programmed Cell Death Ligand-1 Expression in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC). RESEARCH QUESTION: What is the sensitivity and specificity of PD-L1 testing performed in cytologic vs paired histologic specimens in patients with NSCLC? STUDY DESIGN AND METHODS: The MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched through June 1, 2021. The primary outcome was pooled sensitivity and specificity of PD-L1 testing performed on cytologic specimens compared with the reference standard of histologic specimens, analyzed at the PD-L1 expression cutoffs (tumor proportion score) ≥ 1% and ≥ 50%. Pooled sensitivity and specificity, and associated 95% CIs, were estimated using bivariate generalized linear mixed models. RESULTS: Twenty-six articles were included, encompassing a total of 1,064 pairs of histology specimens and cytology cell blocks, and 267 pairs of histology specimens and direct smears. Among these, 946 paired specimens were acquired without interval treatment between the collection of histology and cytology samples. The pooled sensitivity and specificity of cytology specimens compared with paired histology specimens at the PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.77-0.89) and 0.88 (95% CI, 0.82-0.93), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.78 (95% CI, 0.69-0.86) and 0.94 (95% CI, 0.91-0.96), respectively. When only paired specimens acquired without interval treatment were considered, the pooled sensitivity and specificity of cytology specimens at PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.76-0.90) and 0.89 (95% CI, 0.82-0.94), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.80 (95% CI, 0.71-0.89) and 0.94 (95% CI, 0.91-0.96), respectively. INTERPRETATION: Cytologic specimens provide an accurate assessment of PD-L1 expression in most patients with NSCLC, at both ≥ 1% and ≥ 50% cutoffs, when compared with histologic specimens. TRIAL REGISTRATION: PROSPERO; No.: CRD42020153279; URL: https://www.crd.york.ac.uk/prospero/.

Neutralizing antibody and T-cell responses against SARS-CoV-2 variants by heterologous CoronaVac/ChAdOx-1 vaccination in elderly subjects with chronic obstructive pulmonary disease.

BACKGROUND: Data on humoral and cellular immune responses against SARS-CoV-2 after receiving heterologous CoronaVac/ChAdOx-1 (CoVac/ChAd) vaccination in subjects with chronic obstructive pulmonary disease (COPD) are still limited. Therefore, we determined the neutralizing antibody (NAb) and T-cell responses against SARS-CoV-2 wild type (WT) and variants of concern (VOCs) in COPD patients. METHODS: The levels of NAb as well as specific CD4 and CD8 T-cell responses against SARS-CoV-2 WT and VOCs were determined in COPD patients before and after vaccination. RESULTS: Four weeks after vaccinations, the median levels of % inhibition of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants were significantly higher compared to pre-vaccination. The induction of NAb against Omicron was very low compared to other variants. At four weeks after vaccination, in comparison to pre-vaccination, the increasing trend of TNF-α-, IFN-γ-, IL-4-, IL-17-, IL-10-, and FasL-producing CD4 T-cells upon stimulation with WT spike peptides were demonstrated. No difference in T-cell responses to spike peptides of Alpha, Beta, and Delta variants and their WT homologs was observed. CONCLUSION: Heterologous CoVac/ChAd vaccine induced the production of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants, but low for Omicron in COPD patients. Induction of CD4 T-cell subset responses was slightly observed by this vaccine regimen. CLINICAL TRIALS REGISTRY: This study was approved by the Clinical Trials Registry (Study ID: TCTR20210822002).

Clinical Characteristics, Risk Factors, and Outcomes of Acute Pulmonary Embolism in Asian Population.

BACKGROUND: Acute pulmonary embolism (APE) is a common condition with increasing worldwide incidence. However, the clinical characteristics, risk factors, and clinical outcomes of APE in the Asian population especially in the Thai population are still limited. Therefore, the objective of this study was to identify the clinical characteristics, risk factors, and clinical outcomes of APE in the Asian population. METHODS: A cross-sectional study was conducted on patients diagnosed with APE at Chiang Mai University Hospital, Thailand during 2011-2020. RESULTS: During the study period, 696 patients confirmed the diagnosis of APE with a mean age of 57.7 ± 15.7 years and 41.1% males. APE was suspected in 468 of 696 patients (67.2%), while 228 patients (32.8%) had incidental PE. Active malignancy during treatment was found in 388 (55.7%). Dyspnea, cough, and chest pain were the most common presenting symptoms. Respiratory failure was found in 129 patients (18.6%). The thirty-day all-cause mortality rate was 19.1%. PE-related mortality was 5.6%. Most PE-related mortality was high-risk PE. CONCLUSION: APE was not uncommon in the Asian population. Active cancer, especially lung cancer was the most common risk factors. High-risk and intermediate-high-risk PE were associated with high mortality. Risk stratification and prompt management are warranted to improve outcomes.

Neutralizing Antibody and T-Cell Responses against SARS-CoV-2 Wild-Type and Variants of Concern in Chronic Obstructive Pulmonary Disease Subjects after ChAdOx-1/ChAdOx-1 Homologous Vaccination: A Preliminary Study.

Data on immunogenicity of adenovirus-vectored vaccine in chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, we aimed to determine the humoral and cellular immune responses after homologous ChAdOx-1 vaccination in subjects with COPD. COPD subjects and age- and sex-matched healthy elderly receiving ChAdOx-1 homologous vaccination were included. The levels of neutralizing antibodies (NAb) and specific CD4 and CD8 T-cell responses against SARS-CoV-2 wild-type (WT) and variants of concern (VOCs: Alpha, Beta, Delta, and Omicron) were measured. Eight COPD patients were matched with eight control participants. After vaccination for 4 and 12 weeks, % inhibition of NAb against Alpha, Beta, and Delta in both groups were comparable and significantly higher than baseline. The percentage inhibition of NAb at the 12th week was significantly dropped from the 4th week in each group. The NAb against the Omicron variant, however, were much lower than Alpha, Beta, Delta variants. The increasing trend in the number of CD4 T-cells producing TNF-α, IFN-γ, IL-10, and FasL upon stimulation with spike peptides of WT and VOCs was observed in COPD patients compared to the healthy group. These responses were not observed in CD8 T-cells. Homologous ChAdOx-1 vaccination could induce comparable NAb against the SARS-CoV-2 WT, Alpha, Beta, Delta, and Omicron variants between COPD and healthy elderly. The CD4 T-cell responses did not differ between COPD patients and healthy control.

Peripheral Blood Monocyte to Lymphocyte Ratio for Prediction of Tuberculous Pleuritis.

OBJECTIVE: To examine the peripheral monocyte to lymphocyte ratio (ML ratio) of patients with tuberculous (TB) pleuritis and the ML ratio changes after treatment. METHODS: Clinical and laboratory information were collected from patients with lymphocytic exudative pleural effusion admitted to Chiang Mai University Hospital from 2013 to 2019. This study compared the ML ratios between tuberculous pleuritis and other diagnoses in patients who were followed after treatment. RESULTS: A total of 152 patients were included: 57 with tuberculous pleuritis and 95 with other lymphocytic exudates. The majority of non-tuberculous effusion was malignant pleural effusion. The mean ML ratio of each group was 0.72±0.29 and 0.34±0.13 (p<0.001). The Area Under the Receiver Operative Characteristic Curve of the ML ratio for diagnosing tuberculous pleuritis was 0.91. The best cut-off point of the ML ratio for diagnosing tuberculous pleuritis was >0.45, where the sensitivity and specificity were 82.5% and 86.3%, respectively. The ML ratio gradually reduced after the anti-TB treatment. ML ratios at 0, 2, and 6 months after the treatment were 0.72±0.29, 0.40±0.37, and 0.30±0.27, respectively (p<0.001). CONCLUSION: The peripheral blood ML ratio is an easy and useful tool for diagnosing and predicting the treatment response in patients with tuberculous pleuritis.

Overuse of small chest drains for pleural effusions: a retrospective practice review.

PURPOSE: Small-bore drains (≤ 16 Fr) are used in many centers to manage all pleural effusions. The goal of this study was to determine the proportion of avoidable chest drains and associated complications when a strategy of routine chest drain insertion is in place. DESIGN/METHODOLOGY/APPROACH: We retrospectively reviewed consecutive pleural procedures performed in the Radiology Department of the McGill University Health Centre over one year (August 2015-July 2016). Drain insertion was the default drainage strategy. An interdisciplinary workgroup established criteria for drain insertion, namely: pneumothorax, pleural infection (confirmed/highly suspected), massive effusion (more than 2/3 of hemithorax with severe dyspnea /hypoxemia), effusions in ventilated patients and hemothorax. Drains inserted without any of these criteria were deemed potentially avoidable. FINDINGS: A total of 288 procedures performed in 205 patients were reviewed: 249 (86.5%) drain insertions and 39 (13.5%) thoracenteses. Out of 249 chest drains, 113 (45.4%) were placed in the absence of drain insertion criteria and were deemed potentially avoidable. Of those, 33.6% were inserted for malignant effusions (without subsequent pleurodesis) and 34.5% for transudative effusions (median drainage duration of 2 and 4 days, respectively). Major complications were seen in 21.5% of all procedures. Pneumothorax requiring intervention (2.1%), bleeding (0.7%) and organ puncture or drain misplacement (2%) only occurred with drain insertion. Narcotics were prescribed more frequently following drain insertion vs. thoracentesis (27.1% vs. 9.1%, p = 0.03). ORIGINALITY/VALUE: Routine use of chest drains for pleural effusions leads to avoidable drain insertions in a large proportion of cases and causes unnecessary harms.

Real-World Outcomes of Patients With Advanced Non-small Cell Lung Cancer Treated With Anti-PD1 Therapy on the Basis of PD-L1 Results in EBUS-TBNA vs Histological Specimens.

BACKGROUND: Programmed death-ligand 1 (PD-L1) testing is feasible in most specimens acquired using endobronchial ultrasound-guided needle aspiration (EBUS-TBNA). RESEARCH QUESTION: Are the outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) on the basis of PD-L1 expression in EBUS-TBNA samples significantly different from those of patients who are treated on the basis of PD-L1 expression in histological samples? STUDY DESIGN AND METHODS: Patients treated with pembrolizumab or nivolumab between June 2016 and 2019 were included. Patient characteristics, PD-L1 expression, line of treatment, response (Response Evaluation Criteria in Solid Tumors [RECIST] criteria), and vital status (May 14, 2020) were recorded. Progression-free survival (PFS) and overall survival (OS) were assessed, and hazard ratios (HR) estimated. RESULTS: A total of 145 patients were treated with pembrolizumab or nivolumab on the basis of PD-L1 expression in EBUS-TBNA (31.7%) or histological (68.3%) samples. Most had metastatic disease, with a predominance of adenocarcinomas (64.1%). First-line pembrolizumab was administered to 61 patients with tumor proportion score ≥50% in EBUS-TBNA (n = 16) or histology samples (n = 45). Median OS and PFS of patients who received first-line pembrolizumab on the basis of PD-L1 results in EBUS-TBNA vs histology samples were not significantly different (OS 25.8 months vs not reached, respectively; HR, 0.82 [95% CI, 0.34-1.95], P = .651). Similarly, the median OS and PFS of patients who received subsequent lines of treatment on the basis of PD-L1 results in EBUS-TBNA vs histological samples were not significantly different (including after adjustment for PD-L1 expression). INTERPRETATION: These findings suggest that PD-L1 results in EBUS-TBNA samples can guide ICI therapy, with treatment outcomes being comparable to those of patients in whom PD-L1 expression was assessed in histological specimens.

Diagnostic ability of the Timed Up & Go test for balance impairment prediction in chronic obstructive pulmonary disease.

BACKGROUND: Balance assessment is now recommended by clinical practice guidelines, specific tests have yet to be suggested. The Timed Up and Go (TUG) test is a simple measure of balance status and functional mobility. Nowadays, we need more data of an optimum cut off point of TUG time for detecting balance impairment in patients with chronic obstructive pulmonary disease (COPD). Thus the aim of this study was to evaluate the diagnostic ability relative to balance impairment of the TUG in subjects with COPD. METHODS: The cross-sectional study was conducted in stable COPD patient at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand from November 2015 to October 2017. Balance impairment test was measured using the Berg Balance Scale (BBS), a score of ≤45 indicates balance impairment. The TUG was evaluated using sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), Youden's index, and the area under receiver operating characteristic curve (AUROC) from various points of TUG to identify the optimum cut-off point for detecting balance impairment. Multivariable logistic regressions were performed to identify the optimum cut off point of TUG test time for prediction of balance impairment in COPD. RESULTS: One hundred and eighteen smoking related COPD subjects 86 (72.9% male) with a mean age of 73.5±8.1 years were included in this study. Univariable analysis showed that the AUROC of TUG test to indicate those who had impaired balance was 0.93 [95% confidence interval (CI): 0.88, 0.98]. A cut off point of TUG test time ≥12 seconds had sensitivity, specificity, LR+, LR-, Youden's index, and AUROC of 95.8%, 90.4%, 10.01, 0.05, 86.2, and 0.93 for detecting balance impairment, respectively. Multivariable analysis identified the TUG test time ≥12 seconds was the best predictor of balance impairment in COPD patients with adjusted risk ratio (RR) of 25.2 (95% CI: 1.6, 312.0, P=0.021) and, the AUROC was 0.98 (95% CI; 0.96, 1.00). CONCLUSIONS: Our study indicates the TUG test time ≥12 seconds has a high diagnostic ability for balance impairment prediction in COPD. The result supports a potential role for this simple test to be incorporated into routine COPD assessment to stratify patients' balance.

Bronchoscopic tissue yield for advanced molecular testing: are we getting enough?

The treatment of advanced lung cancer has become increasingly personalized over the past decade as a result of the improved understanding of tumor molecular biology and anti-tumor immunity. An adequate tumor sample is central to targetable mutation analysis, and immunologic profiling. The majority of lung cancer patients currently present at an advanced disease stage, so that diagnosis and staging are largely based on small biopsy and cytology specimens. Flexible bronchoscopy techniques play a prominent role in the acquisition of these diagnostic specimens. This narrative review summarizes the available evidence with regards to the role of various conventional and advanced flexible bronchoscopy techniques in acquiring sufficient tissue for mutation analysis and programmed death-ligand 1 (PD-L1) testing.

Intractable pleural effusion in Kaposi sarcoma following antiretroviral therapy in a Caucasian female infected with HIV.

We report the case of a 57-year-old Caucasian woman with AIDS-related disseminated Kaposi sarcoma (KS) characterised by the combination of several unusual features. The chylous nature of the pleural effusions, the documented parietal pleural involvement at thoracoscopy and the marked clinical worsening through an immune reconstitution syndrome following antiretroviral therapy initiation represent several rare situations that occurred in the same female patient. In addition, the use of indwelling pleural catheters for dyspnoea palliation also represents a rare therapeutic intervention. This case is a reminder of the possibility of AIDS-related pleural KS, now uncommon in the era of antiretroviral therapy.

Severe bilateral bronchial stenosis with acute respiratory failure from granulomatosis with polyangiitis.

We report a 48-year-old female patient hospitalized with dyspnoea, wheezing, and respiratory failure due to bilateral main bronchial stenosis from granulomatosis with polyangiitis (GPA) involvement. By computed tomography imaging and flexible bronchoscopy, we measured the narrowest diameter at 2 mm. The patient promptly recovered from respiratory failure after treatment with flexible bronchoscopic balloon dilatation (BBD) without any procedure-related adverse event. This report showed the benefits of urgent flexible BBD that was used as a rescue therapy in a GPA patient who presented life-threatening acute respiratory failure from severe bilateral bronchial stenosis.