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/.

Impact of a Pleural Care Program on the Management of Patients With Malignant Pleural Effusions.

BACKGROUND: Malignant pleural effusions (MPEs) are common and associated with a poor prognosis. Yet, many patients face suboptimal management characterized by repeated, nondefinitive therapeutic procedures and potentially avoidable hospital admissions. METHODS: We conducted a retrospective comparison of patients who underwent a definitive palliative intervention for MPE (indwelling pleural catheter or pleurodesis) at our center, before and after the implementation of a pleural care program. Targeted interventions included staff education, establishment of formal pleural drainage policies, a pleural clinic with weekday walk-in capacity, and a rapid access pathway for oncology patients. Outcomes assessed were the proportion of emergency room (ER) presentations, hospitalizations, number of nondefinitive pleural procedures, and time-to-definitive palliative procedure. RESULTS: A total of 144 patients were included: 69 in the preintervention group and 75 in the postintervention group. Although there was no difference in the proportion of ER presentations before and after interventions (43.5% vs. 38.7%, P =0.56), hospital admissions declined significantly (47.8% vs. 24.0%, P =0.003). The proportion of patients undergoing chest drain insertion decreased significantly (46.4% vs. 13.3%, P <0.001), with a stable low number of nondefinitive procedures per patient (1.6±1.1 vs. 1.3±0.9, P =0.32). A 7-day decrease in median time from presentation-to-definitive palliative procedure ( P =0.05) was observed. CONCLUSION: A targeted pleural care program improved MPE palliation through reduction in hospitalizations and chest drain use, and shorter time-to-definitive palliation, despite failing to reduce ER presentations.

Granulomatous tracheo-bronchitis from Crohn's disease.

Tracheo-bronchitis is an uncommon but important extra-intestinal manifestation of Crohn's disease. Our case demonstrates radiological and bronchoscopic evidence of tracheo-bronchitis secondary to Crohn's disease with pathology-proven granulomatous inflammation. This case highlights the importance of investigating airway involvement in patients with Crohn's disease and new respiratory symptoms.

The Accessibility, Feasibility, and Safety of a Standardized Community-based Tele-Pulmonary Rehab Program for Chronic Obstructive Pulmonary Disease: A 3-Year Real-World Prospective Study.

Rationale: Few individuals with chronic obstructive pulmonary disease (COPD) are able to access pulmonary rehabilitation (PR) despite its importance. Barriers include increased travel time and lack of resources. Tele-PR has been proposed as a novel solution to overcome such barriers and improve access. Objectives: Our study aimed to provide information on implementing a novel province-wide standardized community-based tele-PR program and determine its accessibility, feasibility, and safety. Secondary objectives examined the effectiveness of tele-PR compared with standard PR and if clinical improvements were sustained over time. Methods: We conducted a concurrent prospective study of people with COPD enrolled in either standard PR or community-based tele-PR at satellite centers between January 2017 and January 2020. To determine accessibility and feasibility, we recorded the number of participating centers meeting eligibility criteria, centers remaining in the program over 3 years, number of delivered programs, and major adverse events. Participants had a 6-minute walk test (6MWT) and COPD assessment test (CAT) at baseline, immediately after PR and at 1, 3, 6, and 12 months. Descriptive analysis was performed for accessibility, feasibility, and safety. Mixed-effects random models were used to estimate change in 6MWT and CAT. Results: Seven tele-sites were recruited into the tele-PR program, with six continuing to participate at 3 years, delivering a total of 58 programs for 177 individuals with COPD. During that same period, the standard PR site delivered 15 programs for 89 individuals with COPD. Over 70% of participants completed each program, and no major adverse events were reported. There were significant improvements in the 6MWT and CAT scores in both groups immediately after PR with no between-group differences. Participants in both programs had persistent 6MWT improvement at 1, 3, 6, and 12 months after PR. Participants in tele-PR, but not those in standard PR, had persistent improvements of CAT scores beyond 1 month after PR. Conclusions: This study provides real-world evidence demonstrating successful implementation of tele-PR. The Canadian standardized tele-PR program is an accessible, feasible, safe, and effective model for delivering PR.

Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically significant increase in their absolute number in the MSC group compared to their diluent controls. Investigation of behavior in another cohort of animals showed that delayed administration of a high-dose of bone marrow-derived MSCs, at one week after neonatal rat hypoxia-ischemia, improved motor function on the cylinder test. Thus, delayed therapy with a high- or low-dose of adult MSCs, at one week after injury, is effective in restoring the loss of striatal medium-spiny projection neurons after neonatal rat hypoxia-ischemia and a high-dose of MSCs improved motor function.