Evidence-based opioid prescribing guidelines after lung resection: a prospective, multicenter analysis.

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection. Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation). Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10). Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection.

Implementation and Effectiveness of Opioid Prescribing Guidelines After Hiatal Hernia Repair.

INTRODUCTION: We defined institutional opioid prescribing patterns, established prescribing guidelines, and evaluated the adherence to and effectiveness of these guidelines in association with opioid prescribing after hiatal hernia repair (HHR). METHODS: A retrospective chart review was completed for patients who underwent transthoracic (open) or laparoscopic HHR between January and December 2016. Patient-reported opioid use after surgery was used to establish prescribing recommendations. Guideline efficacy was then evaluated among patients undergoing HHR after implementation (August 2018 to June 2019). Data are reported in oral morphine equivalents (OMEs). RESULTS: The initial cohort included n = 87 patients (35 open; 52 laparoscopic) with a 68% survey response rate. For open repair, median prescription size was 338 mg OME (interquartile range [IQR] 250-420) with patient-reported use of 215 mg OME (IQR 78-308) (P = 0.002). Similarly, median prescription size was 270 mg OME (IQR 200-319) with patient-reported use of 100 mg OME (IQR 4-239) (P < 0.001) for laparoscopic repair. Opioid prescribing guidelines were defined as the 66th percentile of patient-reported opioid use. Postguideline implementation cohort included n = 108 patients (36 open; 72 laparoscopic). Median prescription amount decreased by 54% for open and 43% laparoscopic repair, with no detectable change in the overall refill rate after guideline implementation. Patient education, opioid storage, and disposal practices were also characterized. CONCLUSIONS: Evidence-based opioid prescribing guidelines can be successfully implemented for open and laparoscopic HHR with a high rate of compliance and without an associated increase in opioid refills.

Explanted malignancies after lung transplantation: the University of Michigan experience.

The management of patients with an explanted malignancy after lung transplantation is not well understood. We reviewed our institutional experience and outcomes at a single academic medical centre between December 1997 and April 2021 for patients with malignancies of all histologic types identified on explant pathology. Primary lung cancers were reclassified using the 8th Edition TNM staging and the 2021 World Health Organization histologic classification of lung cancers. Of the 733 patients undergoing lung transplantation, 15 (2.05%) were found to have malignancy on the explanted lungs, including 6 (0.82%) primary lung cancers. Four patients were found to have early-stage lung cancers, while 2 patients had advanced-stage IV disease. Survival ranged from 0 to 109 months for the entire cohort with median 23.2 [49.9] months in those with primary lung cancers. There were 2 recurrences following explanted stage I (15 months) and stage IV (53 months) diseases. Other explant pathologies included carcinoid tumourlets in 6 patients, lymphoma in 2 and metastatic leiomyosarcoma in 1. In conclusion, explanted lung malignancies are an infrequent but significant finding on explant pathology. Further data are needed to better characterize and stratify this patient cohort.

Mechano-inflammatory sensitivity of ACE2: Implications for the regional distribution of SARS-CoV-2 injury in the lung.

The coronavirus disease (COVID-19) caused by SARS-CoV-2 can result in severe injury to the lung. Computed tomography images have revealed that the virus preferentially affects the base of the lung, which experiences larger tidal stretches than the apex. We hypothesize that the expression of both the angiotensin converting enzyme-2 (ACE2) receptor for SARS-CoV-2 and the transmembrane serine protease 2 (TMPRSS2) are sensitive to regional cell stretch in the lung. To test this hypothesis, we stretched precision cut lung slices (PCLS) for 12 h with one of the following protocols: 1) unstretched (US); 2) low-stretch (LS), 5% peak-to-peak area strain mimicking the lung base; or 3) high-stretch (HS), the same peak-to-peak area strain superimposed on 10% static area stretch mimicking the lung apex. PCLS were additionally stretched in cigarette smoke extract (CSE) to mimic an acute inflammatory exposure. The expression of ACE2 was higher whereas that of TMPRSS2 was lower in the control samples following LS than HS. CSE-induced inflammation substantially altered the expression of ACE2 with higher levels following HS than LS. These results suggest that ACE2 and TMPRSS2 expression in lung cells is mechanosensitive, which could have implications for the spatial distribution of COVID-19-mediated lung injury and the increased risk for more severe disease in active smokers and patients with COPD.

A High-Throughput System for Cyclic Stretching of Precision-Cut Lung Slices During Acute Cigarette Smoke Extract Exposure.

RATIONALE: Precision-cut lung slices (PCLSs) are a valuable tool in studying tissue responses to an acute exposure; however, cyclic stretching may be necessary to recapitulate physiologic, tidal breathing conditions. OBJECTIVES: To develop a multi-well stretcher and characterize the PCLS response following acute exposure to cigarette smoke extract (CSE). METHODS: A 12-well stretching device was designed, built, and calibrated. PCLS were obtained from male Sprague-Dawley rats (N = 10) and assigned to one of three groups: 0% (unstretched), 5% peak-to-peak amplitude (low-stretch), and 5% peak-to-peak amplitude superimposed on 10% static stretch (high-stretch). Lung slices were cyclically stretched for 12 h with or without CSE in the media. Levels of Interleukin-1ß (IL-1ß), matrix metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP1), and membrane type-MMP (MT1-MMP) were assessed via western blot from tissue homogenate. RESULTS: The stretcher system produced nearly identical normal Lagrangian strains (E xx and E yy , p > 0.999) with negligible shear strain (E xy < 0.0005) and low intra-well variability 0.127 ± 0.073%. CSE dose response curve was well characterized by a four-parameter logistic model (R 2 = 0.893), yielding an IC50 value of 0.018 cig/mL. Cyclic stretching for 12 h did not decrease PCLS viability. Two-way ANOVA detected a significant interaction between CSE and stretch pattern for IL-1ß (p = 0.017), MMP-1, TIMP1, and MT1-MMP (p < 0.001). CONCLUSION: This platform is capable of high-throughput testing of an acute exposure under tightly-regulated, cyclic stretching conditions. We conclude that the acute mechano-inflammatory response to CSE exhibits complex, stretch-dependence in the PCLS.

Topographic distribution of idiopathic pulmonary fibrosis: a hybrid physics- and agent-based model.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by excessive deposition of collagen and associated stiffening of lung tissue. While it is known that inflammation and dysfunction of fibroblasts are involved in disease development, it remains poorly understood how cells and their microenvironment interact to produce a characteristic subpleural pattern of high and low tissue density variations, called honeycombing, on CT images of patients with IPF. Since the pleura is stiffer than the parenchyma, we hypothesized that local stiffness of the underlying extracellular matrix can influence fibroblast activation and consequently the deposition of collagen, which in turn influences tissue stiffness in a positive feedback loop. APPROACH: We tested this hypothesis by developing a hybrid physics-based/agent-based computational model in which aberrant fibroblast activation is induced when cells migrate on stiff tissue. This activation then feeds back on itself via the altered mechanical environment that it creates by depositing collagen. MAIN RESULTS: The model produces power law distributions of both low- and high-attenuation area clusters and predicts the development of honeycombing only when mechanical rupture is allowed to take place in highly strained normal tissue surrounded by stiff fibrotic tissue. These predictions compare well with histologic data computed from CT images of patients with IPF. SIGNIFICANCE: We conclude that the clinical manifestation of subpleural honeycombing in IPF may result from fibroblasts entering into a positive feedback loop induced by the abnormally high tissue stiffness near the pleura.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.