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BACKGROUND: Additional data regarding the ability of navigational bronchoscopy (NB) to provide sufficient material for programmed death-ligand 1 (PD-L1) expression is needed. We performed a retrospective study of NB cases at our institution to determine performance of NB in providing adequate samples for PD-L1. METHODS: We conducted a retrospective review of all consecutive NB procedures performed at our institution from January 1, 2018 to August 4, 2020 that involved biopsies of a lung nodule/mass with a diagnosis of non-small cell lung cancer (NSCLC). The primary outcome was adequacy of material for PD-L1 testing. All procedural, demographic, and diagnostic data were collected. The association of factors with PD-L1 adequacy was evaluated with rate ratios (RR) using modified Poisson regression models with robust standard errors. RESULTS: A total of 102 NB procedures with a diagnosis of NSCLC were performed over a 2-year period. The mean [standard deviation (SD)] nodule size was 25.0 [interquartile range (IQR), 18.0–32.0] mm and 57.8% (59/102) had a bronchus sign; 73% (68/93, 9 missing data) of samples were adequate for PD-L1 testing. Radial endobronchial ultrasound (REBUS) was utilized in 99% (101/102) of biopsies; a concentric or eccentric view was observed in 78.2% (79/101) and 16.8% (17/101), respectively. Transbronchial biopsy (TBBX) was performed in 92.2% (94/102). Only 4% (4/102) of cases required additional biopsies with either computed tomography (CT) guided transthoracic or surgical biopsies due to insufficient bronchoscopy tissue. No factors were predictive of PD-L1 adequacy in regression models. CONCLUSIONS: NB demonstrated good performance in obtaining adequate samples for PD-L1 testing. Only 4% of patients required additional procedures for more tissue when clinically indicated. However, additional study is needed to validate these results against surgical resection specimens.

Summary Background COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. Methods DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov , NCT04350593 . Findings Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58–1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97–1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52–1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. Interpretation In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. Funding AstraZeneca.

Background Navigational bronchoscopy is commonly used to sample lung nodules, with a better safety profile but lower diagnostic yield than computerized tomography-guided transthoracic needle biopsy. The addition of digital tomosynthesis to electromagnetic navigation, using intraprocedural images obtained from a C-arm fluoroscope to identify target lesion location and update navigational guidance, may improve diagnostic yield. Methods Consecutive bronchoscopies using tomosynthesis-assisted fluoroscopic electromagnetic navigational bronchoscopy (F-ENB) at a single institution over a 1-year period were included. The primary outcome was diagnostic yield. A bronchoscopy was defined as diagnostic if pathologic examination revealed malignancy or specific histological findings indicative of lesional sampling with confirmatory 6-month follow-up for benign lesions. Results A total of 324 patients with 363 nodules underwent F-ENB between April 25, 2018 and April 29, 2019. The average nodule size was 1.9±1.1 cm, 65% of the nodules were located in the peripheral third of the lung. A bronchus sign was present in 24% of cases. Of the 363 nodules, 299 (82.4%) had lesional findings. At 6-month follow-up, among these 299 nodules, 6 were found to be false negatives and 12 nodules were lost to follow-up. Considering all nodules lost to follow-up as false negatives, the 6-month diagnostic yield was 77.4%. Pneumothorax complicated 8 (2.5%) of cases. There was 1 episode of respiratory failure. Conclusion This retrospective study suggests the diagnostic yield of F-ENB may exceed that of traditional ENB. Future prospective and comparative studies are needed to confirm these promising data.

Context.— Precision therapies for patients with driver mutations can offer deep and durable responses that correlate with diagnosis, metastasis prognosis, and improvement in survival. The use of such targeted therapies will continue to increase, pushing us to change our traditional approaches. We needed to search for new tools to effectively integrate technological advancements into our practices because of their capability to improve the efficiency and accuracy of our diagnostic and treatment approaches. Perhaps nothing is as relevant as identifying and implementing new workflows for processing pathologic specimens and for improving communication of critical laboratory information to and from clinicians for appropriate care of patients in an efficient and timely manner. Objectives.— To define the gold standard in delivering the best care for patients, to identify gaps in the process, and to identify potential solutions that would improve our process, including gaps related to knowledge, skills, attitudes, and practices. Design.— We assembled a multidisciplinary team to systematically perform a gap analysis study to clarify the discrepancy between the current reality in pathology specimen processing and the desired optimal situation to deliver the results intended for patient care. Results.— A practical collaborative workflow for specimen management that seeks the cooperation of stakeholders in each medical discipline to provide guidelines in specimen collection, delivery, processing, and reporting of results with the ultimate goal of improving patient outcomes is provided. Conclusions.— New tools are required to effectively integrate data-driven approaches in specimen processing to meet the new demands.

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Introduction: Indwelling pleural catheters (IPC) are effective at palliating benign and malignant pleural effusions (MPE). They have also been found to be cost effective from a third-party payor perspective. Little is known of the impact IPCs have on patient-centered quality of life outcomes such as financial burden and patient and caregiver burden. We performed a cross-sectional survey study evaluating the impact of IPCs on multiple patient and caregiver quality of life metrics. Methods: Patients ≥ 18 years old with an IPC in place for 2 months were eligible. Twenty patients were recruited over a 10-month period. Patients completed the CDC-Health Related Quality of Life (HRQOL)-4 and a HRQOL-financial questionnaire. The primary objective was to describe the socio-economic impact of IPCs. Demographic and IPC specific data were collected. Descriptive statistics were used. Results: The mean (SD) age was 64.3 (0.70). The indication was MPE in 19/20. All patients had medical insurance. Medicare or Medicaid (CMS) comprised 10/20 of payors. The median (IQR) copay for private insurers was $238.45 (72-875); 11/20 had additional costs related to the IPC; 4/20 had significant life changes after the IPC; 17/20 received assistance from a non-paid caregiver; 6/20 patients could not do activities because of the IPC and this negatively impacted QOL in 3/6 of those patients. Conclusion: Patients with IPCs may experience negative life consequences, incur additional medical expenses, and require assistance from a non-paid caregiver. Activities may be negatively impacted by IPC. Discussion of alternative means of symptom palliation and pleurodesis would be beneficial.

Background Major airway bleeding is the most feared complication of transbronchial cryobiopsy (TBC). Radial endobronchial ultrasound (REBUS) has been used to assess the peripheral lung, primarily to identify pulmonary nodules, and also peripheral blood vessels. Using REBUS-guided TBC to avoid peripheral vasculature might reduce bleeding risk. This prospective randomized double-blind pilot trial was designed to investigate the feasibility of study procedures and inform the power calculation and clinical significance of a future large randomized trial. Methods Consecutive TBCs were randomized to be performed with or without REBUS guidance in the same patient. A nonblinded operator obtained each biopsy while a blinded second operator managed the bleeding after each biopsy and determined when hemostasis had been obtained. Feasibility of study procedures and the ability to recruit patients were of primary interest. Time to hemostasis after each biopsy was also examined. Results Forty TBCs were performed in 10 patients (4 biopsies per patient) over an enrollment period of 6 months. The time to control bleeding between biopsies was not statistically different between intervention and control arms [-14.3 (-120.1 to 92.0) s, P=0.7878]. Mean bleeding time was 139.4±59.895 seconds (REBUS 132.25± 89.305 s, non-REBUS 146.55±82.043 s). A trend towards the decreased grade of bleeding and less need for additional interventions was observed with REBUS use, but this difference did not reach statistical significance in this pilot investigation. Conclusion Our findings suggest that REBUS-guided TBC is feasible. We did not observe any statistically significant difference in time to hemostasis or bleeding grade in this pilot study.

Primary blast lung injury (PBLI) is defined as lung contusion from barotrauma following an explosive mechanism of injury (MOI). Military data have focused on PBLI characteristics following evacuation from the combat theatre; less is known about its immediate management and epidemiology in the deployed setting. We conducted a quality improvement project to describe the prevalence, clinical characteristics, management strategies and evacuation techniques for PBLI patients prior to evacuation.Patients admitted to a Role 3 hospital in southwest, Afghanistan, from January 2008 to March 2013 with a blast MOI were identified through the Department of Defense Trauma Registry; International Classification of Diseases 9 codes and patient record review were used to identify the PBLI cohort from radiology reports. Descriptive statistics and Fishers exact test were used to report findings.Prevalence of PBLI among blast injured patients with radiology reports was 11.2% (73/648). The population exhibited high Injury Severity Scores median 25 (IQR 14-34) and most received a massive blood transfusion (mean 33.4±38.3 total blood products/24 h). The mean positive end expiratory pressure (PEEP) requirement was 6.2±3.7 (range 5-15) cm H2O and PaO2 to FiO2 ratio was 297±175.2 (66-796) mm Hg. However, 16.6% of patients had a PaO2 to FiO2 ratio200, 13.3% required PEEP ≥10 cm H2O and one patient required specialised evacuation for respiratory failure. A dismounted MOI (72.8%) and evacuation from point of injury by the Medical Emergency Response Team (62.3%) appeared to be associated with worse lung injury. Only eight of the 73 PBLI patients died and of the five with retrievable records, none died from respiratory failure.PBLI has a low prevalence and conventional lung protective ventilator management is generally appropriate immediately after injury; application of advanced modes of ventilation and specialised evacuation assistance may be required. PBLI may be a marker of underlying injury severity since all deaths were not due to respiratory failure. Further work is needed to determine exact MOI in mounted and dismounted casualties.

Background Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. Study Design Pilot randomized double-blind placebo-controlled trial. Setting & Participants 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. Intervention Pentoxifylline, 400 mg twice daily, or matching placebo. Outcomes Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. Measurements Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. Results Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (−1.2 ± 7.0 versus −7.2 ± 8.2 mL/min/1.73 m 2 /y; mean difference, −6.0 mL/min/1.73 m 2 /y; 95% confidence interval, −11.4 to −0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (−9.6 ± 11.9 mL/min/1.73 m 2 /y; mean difference, −8.4 mL/min/1.73 m 2 /y; 95% confidence interval, −14.8 to −2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. Limitations Small sample size and incomplete follow-up. Conclusions Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.

Dexmedetomidine has become a popular sedative in the intensive care unit for patients undergoing mechanical ventilation because of its highly selective α-2 agonism, which exerts a combination of anesthetic, analgesic, and anxiolytic effects. Bradycardia and hypotension have been reported as the most common side effects of its use in large studies. Dexmedetomidine has been reported to induce polyuria by suppressing vasopressin secretion and increasing permeability of the collecting ducts in a dose-dependent fashion. We report a case of dexmedetomidine-related polyuria that occurred with a high-dose continuous infusion and subsequently resolved with discontinuation of the drug. (Anesth Analg 2013;117:150-2).

Dexmedetomidine has become a popular sedative in the intensive care unit for patients undergoing mechanical ventilation because of its highly selective α-2 agonism, which exerts a combination of anesthetic, analgesic, and anxiolytic effects. Bradycardia and hypotension have been reported as the most common side effects of its use in large studies. Dexmedetomidine has been reported to induce polyuria by suppressing vasopressin secretion and increasing permeability of the collecting ducts in a dose-dependent fashion. We report a case of dexmedetomidine-related polyuria that occurred with a high-dose continuous infusion and subsequently resolved with discontinuation of the drug. (Anesth Analg 2013;117:150-2).

Published analyses of clinical outcomes for patients requiring large-volume blood transfusion conflict with respect to the impact upon plasma potassium levels. We analyzed a cohort of trauma patients to ascertain the impact of component product transfusion upon plasma potassium values.We performed an observational analysis of previously, prospectively collected clinical data on 131 noncrush trauma patients undergoing resuscitation during the initial 12 hours after admission to a combat support hospital. Comparisons were made between those who received packed red blood cell (PRBC) transfusion and those who did not. Primary outcome was hyperkalemia (plasma potassium level5.5 mmol/L).Ninety-six of one hundred thirty-one patients (73.3%) received PRBCs (mean number of PRBC units 11.2, range, 0-55.0). For transfusion versus nontransfusion patients, baseline plasma potassium value (3.7 +/- 0.57 mmol/L vs. 3.6 +/- 0.36 mmol/L, p = 0.22) rose significantly after transfusion (5.3 +/- 1.2 mmol/L, vs. 4.0 +/- 0.78 mmol/L, p0.001). During the study period, 38.5% of transfusion patients developed hyperkalemia, versus 2.9% of those who did not (p = 0.003). In multivariate logistic regression analysis, transfusion of greater than 7 units of PRBCs was independently associated with the development of hyperkalemia (RR 4.72, 95% CI 1.01-21.97, p = 0.048). Transfusion of other cell-based products, baseline base deficits, and plasma bicarbonate levels were not. Spearman's rank correlation coefficient for the relationship of number of transfused PRBC units to the highest recorded potassium value was 0.554 (p0.001). The predictive accuracy of the logistic regression model for hyperkalemia was 0.824 (95% CI 0.747-0.901, p0.001).Hyperkalemia is common after PRBC transfusion, and often severe. PRBC transfusion is independently associated with the development of hyperkalemia. The findings suggest the need for interventional studies examining the impact of alternative resuscitative approaches after severe trauma.

Dear Sir, We recently published a quality improvement project (QIP) describing the prevalence, clinical characteristics, management, and evacuation strategies in primary blast lung injury (PBLI) during combat operations in Afghanistan.[1][1] From that study, two questions arose. It appeared that

Teflon-coated pledgeted sutures can be used to reinforce the bronchial anastomosis site following a pulmonary resection in order to prevent bronchopleural fistula formation. The authors describe the case of a 42-year-old woman with recurrent haemoptysis secondary to the erosion of a pledgeted suture through the distal trachea. The pledgeted suture was used to reinforce a defect in the wall of the distal trachea after a right upper lobectomy for stage 2a squamous cell carcinoma. Surgically, a completion pneumonectomy with carinal reconstruction was thought necessary to treat the haemoptysis. Given her age and potential surgical morbidities, the decision was made to perform serial bronchoscopies with careful pruning and eventual removal of the pledget by using the cryoprobe and a flexible scissors. This resulted in the eventual removal of the suture. Follow-up bronchoscopy 4 weeks postremoval demonstrated no residual defect on the airway wall.