Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and PD-L1 Yields.

PURPOSE: Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485-493, 2020; Perrotta et al. in Chest 158: 1230-1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417-1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens. METHODS: Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department. RESULTS: The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%). CONCLUSION: EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.

Pathophysiology and Management of Neurogenic Pulmonary Edema in Patients with Acute Severe Brain Injury.

Acute brain injury (ABI) consists of any acquired insult to the brain and is a significant cause of morbidity and mortality worldwide. Approximately 20% to 30% of patients with ABI develop a lung injury called neurogenic pulmonary edema (NPE), and its development often results in poor outcomes. This article provides a narrative review of the evidence regarding proposed mechanisms of injury, diagnosis, and treatment of NPE in the critical care setting. PubMed and Ovid databases were searched for observational or prospective studies relevant to the diagnosis and treatment of NPE. Overall, studies showed that although the specific mechanisms responsible for NPE remain uncertain, putative mechanisms include vaso- and venoconstriction, catecholamine release with resultant pulmonary vasoconstriction called the "blast injury theory," increased vagal tone, and increased capillary permeability. Diagnosis involves identifying signs of pulmonary edema in patients who experienced a neurologic insult. Management strategies aim to address both brain and lung injury, and treatment modalities appear to work best when balanced toward maintaining a normal physiologic state. In summary, NPE is an often underdiagnosed but important sequela of ABI, which may result in additional long-term morbidity. It is therefore an important entity for providers to recognize and tailor their clinical approach toward.

Sedation challenges in patients with E-cigarette, or vaping, product use-associated lung injury (EVALI).

E-cigarette, or vaping, product use-associated lung injury (EVALI) has become an epidemic that is increasingly affecting patients across USA. Recently, over 2100 cases have been reported in 49 states, resulting in at least 42 deaths. We present a case of rapid respiratory failure in an otherwise healthy and young patient who used a vaporiser containing tetrahydrocannabinol (THC) during the month prior to admission. The patient eventually required mechanical ventilation. There were significant challenges in achieving the appropriate level of sedation during intubation and mechanical ventilation. As more EVALI cases are being diagnosed in recent months, we highlight an aspect that may be unique to the population of patients who vaporise THC-high sedative and analgesic requirements during intubation and mechanical ventilation.

Pattern and Adherence to Maintenance Medication Use in Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease: 2008-2013.

Background: Maintenance medications provide symptomatic relief, improve lung function and reduce the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Despite their proven benefits, limited information exists on maintenance medication use and adherence among users. Objective: We examined the patterns and factors associated with the receipt of and adherence to maintenance medication in individuals with COPD. Methods: A retrospective cross-sectional study of 5% of Medicare beneficiaries enrolled in Parts A, B and D with COPD who received maintenance medication from 2008 to 2013 was conducted. Maintenance medication includes: inhaled corticosteroids (ICSs), long-acting beta2- agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) alone or in combination. We examined the proportion of beneficiaries with COPD who had at least one prescription filled for maintenance medication. Among users of maintenance medications, we also examined adherence, defined as proportion of days covered (PDC) ≥80% over the year from the first maintenance medication prescription fill date. Results: Overall, maintenance medication (LAMAs, LABAs, ICSs and/or LABA/ICS) use increased from 67.8% in 2008 to 72.1% in 2013. The increase is related to increases in use of LABA/ICS, which rose from 41.1% in 2008 to 49.6% in 2013. Factors associated with receipt of maintenance medication include female gender, recent COPD hospitalization (odds ratio [OR] 1.63; 95% confidence interval [CI] 1.54-1.73), oxygen therapy (OR 1.74 95% CI, 1.68-1.81), dual eligibility status (OR 1.45; 95% CI 1.39-1.51), higher education level and evaluation by a pulmonary provider (OR 1.88; 95% CI 1.81-1.96). The overall adherence among maintenance medication users remained flat. The most important factor associated with adherence was dual eligibility status (OR, 1.67; 95% CI: 1.59-1.75). Conclusions: Receipt of maintenance medications increased during the study period and was higher in those with dual eligibility. Overall, adherence to maintenance medications was suboptimal and remained unchanged.

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease.

AIM: To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS: Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS: Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION: PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

Diurnal and nocturnal variations in aqueous humor dynamics of patients with ocular hypertension undergoing medical therapy.

OBJECTIVE: To evaluate the interaction of intraocular pressure(IOP)­lowering medications with physiologic day and night changes in aqueous humor dynamics in participants with ocular hypertension. METHODS: Thirty participants were enrolled in thisdouble-masked, randomized, crossover study. Each participant underwent aqueous humor dynamics measurements at baseline and at 2 weeks of dosing in random order with latanoprost in the evening and placebo in the morning, timolol maleate twice daily, and dorzolamide hydrochloride twice daily. Measurements included central corneal thickness by ultrasound pachymetry, anterior chamber depth by A-scan, seated and habitual IOP by pneumatonometry, blood pressure by sphygmomanometry,episcleral venous pressure by venomanometry,and aqueous flow by fluorophotometry. Outflow facility was assessed by fluorophotometry and by tonography. Uveoscleral outflow was mathematically calculated using the Goldmann equation. RESULTS: Latanoprost use significantly decreased IOP during the day and night. It increased daytime uveoscleral outflow by a mean (SD) of 0.90 (1.46) µL/min (P=.048), but a nighttime increase of 0.26 (1.10) µL/min (P=.47)did not reach statistical significance. Timolol use decreased IOP during the day by reducing aqueous flow by 25%. Dorzolamide use lowered IOP only at the noon measurement and reduced daytime aqueous flow by 16%. Neither dorzolamide nor timolol use added to the physiologic 47% reduction in nighttime aqueous flow. CONCLUSIONS: The daytime IOP-lowering effects of latanoprost are mediated by an increase in uveoscleral outflow,and those of timolol and dorzolamide are mediated by aqueous flow suppression. Nighttime physiologic changes in uveoscleral outflow limit the nighttime pharmacodynamic efficacy of latanoprost. Aqueous flow suppression with timolol and dorzolamide was ineffective in obtaining IOP lowering at night.