How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

OBJECTIVES: The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA: Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. METHODS: From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS: Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. CONCLUSIONS: Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Successful treatment of pulmonary mucormycosis (Lichtheimia spp.) in a post-partum patient with COVID-19 ARDS requiring extra-corporeal membrane oxygenation using salvage therapy.

Case Summary: A 31-year-old female presented to a regional hospital at 27 weeks pregnant and was found to have COVID-19 ARDS. She underwent intubation and caesarian section for worsening hypoxia and non-reassuring fetal heart tones. Hypoxemia was refractory to proning requiring ECMO and transfer to a tertiary care center. Admission chest radiography showed a new right lower lobe cavitating lesion with computed tomography scan revealing a large multi-loculated cavity in the right lung and extensive bilateral ground-glass opacities. The patient was started on amphotericin and posaconazole, with final respiratory cultures growing Lichtheimia spp. Source control was discussed via possible open thoracostomy, but medical management alone was continued. Total ECMO support was 3 weeks. At the time of discharge to acute rehab, 1 month of amphotericin and posaconazole had been completed, with continuation of posaconazole. At last update, she had been discharged from rehab and was back home with her infant. Conclusion: Pulmonary mucormycosis, even in the non-ECLS population, carries a high mortality. Treatment in pulmonary disease with surgery improves mortality but is not always feasible. Salvage therapy with extended course antifungal medications may be an option for those not amendable.

Navigating Informed Consent and Patient Safety in Surgery: Lessons for Medical Students and Junior Trainees.

AbstractIn the operating room, patient safety is of paramount importance. Medical students and junior trainees, despite their primary role as students, may play active roles in assessing patient safety and reporting suspected errors. Active consent is one layer of patient safety that is continuously assessed by several team members. This article examines an instance where patient consent may have been violated. Through the lens of trainee and senior perspectives, we discuss the ethical principles at stake and provide recommendations for medical student and junior trainee involvement in patient care when an error is suspected.

An institution-wide tracheostomy rounding team: Initial caregiver perceptions.

PURPOSE: To analyze and present the initial findings of provider perceptions regarding the impact of the implementation of a hospital-wide Tracheostomy Rounding Team (TRT) on the delivery of tracheostomy care at the Cleveland Clinic. MATERIALS AND METHODS: Based on prior literature, a novel multidisciplinary TRT was designed and implemented at the Cleveland Clinic in December of 2018. After the TRT began clinical care, a previously validated RedCap survey was administered anonymously to 358 caregivers to assess provider experience, comfort, and prior education regarding tracheostomy management. Survey results were collected, and descriptive statistics were applied. Answers were compared between providers who interacted with the TRT clinically and those who did not. RESULTS: 42.9% of providers who interacted with the TRT clinically reported that the TRT improved hands-on assistance with tracheostomy care, and 36.7% reported that the TRT improved the identification of safety concerns. Similarly, 34.7% reported that the TRT improved the overall quality of tracheostomy care at the Cleveland Clinic. Providers with active exposure to the TRT additionally reported statistically higher comfort with multiple topics surrounding tracheostomy care. CONCLUSIONS: The implementation of this team improved provider comfort in managing patients with tracheostomies both qualitatively and quantifiably. This intervention offered a perceived benefit to patient care at our institution. Further study of the impact of this team on quantitative patient outcomes is forthcoming.

A case of vaping-induced acute respiratory distress syndrome requiring extracorporeal life support.

INTRODUCTION: An upsurge of e-cigarette, or vaping, product use-associated lung injury has been reported in the United States. The potential role of extracorporeal life support in e-cigarette, or vaping, product use-associated lung injury merits consideration. CASE REPORT: We present a case of vaping-induced severe acute respiratory distress syndrome that was salvaged with extracorporeal life support and had excellent recovery. DISCUSSION: The mechanistic reasons for the sudden outbreak of e-cigarette, or vaping, product use-associated lung injury are under active investigation. A predominantly diffuse, bilateral pattern of lung injury has been reported, with some cases meeting the criteria for severe acute respiratory distress syndrome. To date, 68 deaths from e-cigarette, or vaping, product use-associated lung injury have been confirmed by the centers of disease control. However, resolution of lung injury has been reported in most cases, thereby justifying candidacy for extracorporeal life support, if required. CONCLUSION: Extracorporeal life support can be successfully utilized as a bridge to recovery in vaping-induced severe acute respiratory distress syndrome.

Continuous infusion chemotherapy, radiotherapy, and FDG-PET are feasible during extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) may be used in extreme circumstances for patients with a mediastinal mass and respiratory failure. We report on a young man with primary mediastinal B-cell lymphoma invading into the trachea, requiring a 40-day ECMO run who underwent fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and treatment with concurrent mediastinal irradiation and continuous infusion chemotherapy while on this life-saving technology. This case illustrates that oncology patients may be managed by multidisciplinary teams for extended periods in extraordinary circumstances using multimodality therapies. Additionally, to our knowledge this is the first case to demonstrate the feasibility of FDG-PET imaging while on ECMO.

Extracorporeal cardiopulmonary resuscitation in a patient with fulminant pulmonary embolism refractory to intraarrest thrombolysis.

INTRODUCTION: A fulminant pulmonary embolism is a potentially reversible cause of cardiac arrest with a reported mortality rate of up to 95%. Therapeutic strategies for fulminant pulmonary embolism continue to evolve. CASE REPORT: We present a case of a 38-year-old female who suffered an in-hospital cardiac arrest due to fulminant pulmonary embolism. Extracorporeal cardiopulmonary resuscitation (facilitated by the LUCAS™ mechanical chest compression device) was successfully performed in this patient following failure of intraarrest thrombolysis. DISCUSSION: For the management of fulminant pulmonary embolism, utilization of clot-directed therapies, especially intraarrest thrombolysis, has garnered increasing traction and interest. However, this therapeutic approach has its limitations. Fortuitously, the emergence of extracorporeal cardiopulmonary resuscitation has added a new dimension to the treatment of fulminant pulmonary embolism. A protocolized approach to treatment can improve outcomes in these patients. CONCLUSION: Extracorporeal cardiopulmonary resuscitation can be used as a salvage therapy in patients with fulminant pulmonary embolism in whom intraarrest thrombolysis has failed.

Correction to: Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.

The following disclaimer is missing from the original article.

Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.

BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival. METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression. RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p < 0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy. CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.

DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.

Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell membrane-associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we took advantage of a clinically relevant mouse model of transplant-mediated lung IRI. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.

Surgical Diaphragm: Anatomy and Physiology.

The diaphragm is a musculoaponeurotic structure separating the thoracic and abdominal cavities. It plays important roles in both respiration and maintaining gastrointestinal function. A careful consideration of anatomy should be taken during surgical procedures to minimize injury to this crucial organ.

Are adult thoracic patient education materials designed with patients in mind?

OBJECTIVE: Patients are increasingly using the internet to obtain health care information. US News and World Report Best Hospital rankings received more than 103 million views in 2021. Considering 21% of thoracic surgery patients are minorities, 27.9% are in the bottom quartile of household income, and 70% have Medicare/Medicaid or no insurance, online patient educational materials (PEMs) should be accessible and written at a level easily understood by majority of patients. We performed a comprehensive analysis of readability of websites containing patient-centered resources across all adult thoracic surgery areas. METHODS: Online PEMs on thoracic surgical procedures were collected from top 50 hospitals for pulmonology and lung surgery ranked by US News and World Report Best Hospital as of December 1, 2021. Text pertaining to thoracic surgical procedures was collected and divided into 4 procedural genres: esophageal, lung, transplant procedures, and other. Texts were analyzed using OleanderSoftware's Readability Suite through the Raygor readability test. RESULTS: Three hundred seventy-two articles met criteria for analysis. Websites were difficult to read; mean (standard deviation) readability score for all content required a 13.9 (3.6) grade level for comprehension. The mean (standard deviation) readability for esophageal, lung, lung transplant, and other surgeries were 14.5 (3.6), 13.1 (3.6), 11.5 (3.9), and 13.4 (3.7), respectively. CONCLUSIONS: Online PEMs required at least a college reading level to comprehend, well exceeding the sixth-grade level recommended by the American Medical Association. As digital health becomes increasingly relevant, improving the readability of online PEMs in adult cardiac surgery will facilitate equitable access to high-quality care.

Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).

OBJECTIVE: Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL). METHODS: The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness. RESULTS: Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59). CONCLUSIONS: We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases.

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging.

BACKGROUND: Inaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. METHODS: From 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. RESULTS: Of the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. CONCLUSIONS: The presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Multi-institutional beta testing of a novel cervical esophagogastric anastomosis simulator.

Objective: A novel simulator developed to offer hands-on practice for the stapled side-to-side cervical esophagogastric anastomosis was tested previously in a single-center study that supported its value in surgical education. This multi-institutional trial was undertaken to evaluate validity evidence from 6 independent thoracic surgery residency programs. Methods: After a virtual session for simulation leaders, learners viewed a narrated video of the procedure and then alternated as surgeon or first assistant. Using an online survey, perceived value was measured across fidelity domains: physical attributes, realism of materials, realism of experience, value, and relevance. Objective assessment included time, number of sutures tearing, bubble test, and direct inspection. Comparison across programs was performed using the Kruskal-Wallis test. Results: Surveys were completed by 63 participants as surgeons (17 junior and 20 senior residents, 18 fellows, and 8 faculty). For 3 of 5 tasks, mean ratings of 4.35 to 4.44 correlated with "somewhat easy" to "very easy" to perform. The interrupted outer layer of the anastomosis rated lowest, suggesting this task was the most difficult. The simulator was rated as a highly valuable training tool. For the objective measurements of performance, "direct inspection" rated highest followed by "time." A total of 90.5% of participants rated the simulator as ready for use with only minor improvements. Conclusions: Results from this multi-institutional study suggest the cervical esophagogastric anastomosis simulator is a useful adjunct for training and assessment. Further research is needed to determine its value in assessing competence for independent operating and associations between improved measured performance and clinical outcomes.

Radiation Exposure in Extracorporeal Life Support.

Extracorporeal membrane oxygenation (ECMO) exposes patients to multiple radiologic studies. We hypothesized ECMO patients endure radiation exposure in excess of the International Commission of Radiological Protection (ICRP) recommendations of cumulative effective dose (CED, >20 mSv and 5-year cumulative limit of CED >100 mSv). We conducted a retrospective observational study in an academic medical center between January 2016 and December 2018 involving adult admissions (N = 306) on ECMO. Ionizing radiation was calculated from reference values to determine CED. Approximately 9.4% (N = 29) patients accrued CED >50 mSv and 4.5% (N = 14) accrued CED >100 mSv during ECMO. Over the entire hospitalization, 28% (N = 85) accrued >50 mSv and 14.7% (N = 45) accrued CED >100 mSv. Median CED during ECMO was 2.3 mSv (IQR, -0.82 to 8.1 mSv), and the entire hospitalization was 17.4 mSv (IQR, -4.5 to 56.6 mSv). Thirteen percent of the median CED accrued during hospitalization could be attributed to ECMO. Longer hospitalization was associated with a higher CED (50 days [IQR, -25 to 76 days] in CED >50 vs. 19 days [IQR, -10 to 32 days] in CED <50). Computer tomography (CT) scans and interventional radiology (IR) procedures contributed to 43.8% and 44.86%, respectively, of CED accrued on ECMO and 52.2% and 37.1% of CED accumulated during the whole hospitalization. Guidelines aimed at mitigating radiation exposure are urgently needed.

Preoperative predictors of spread through air spaces in lung cancer.

OBJECTIVE: Spread through air spaces (STAS) is a new histologic feature of invasion of non-small cell lung cancer that lacks sensitivity and specificity on frozen sections and is associated with higher recurrence and worse survival with sublobar resections. Our objective is to identify preoperative characteristics that are predictive of STAS to guide operative decisions. METHODS: From January 2018 through December 2021, 439 cT1-3N0 M0 patients with non-small cell lung cancer and a median age of 68 years, 255 (58%) women, who underwent primary surgery at our institution were included. Patients who received neoadjuvant therapy and whose STAS status was not documented were excluded. Age, sex, smoking status, tumor size, ground-glass opacities, maximum standardized uptake values, and molecular markers on preoperative biopsy were evaluated as preoperative markers. Comparisons between groups were conducted using standardized mean differences and random forest classification was used for prediction modeling. RESULTS: Of the 439 patients, 177 had at least 1 STAS-positive tumor, and 262 had no STAS-positive tumors. Overall, 179 STAS tumors and 293 non-STAS tumors were evaluated. Younger age (50 years or younger), solid tumor, size ≥2 cm, and maximum standardized uptake value ≥2.5 were independently predictive of STAS with prediction probabilities of 50%, 40%, 38%, and 40%, respectively. STAS tumors were more likely to harbor KRAS mutations and be PD-L1 negative. CONCLUSIONS: Young age (50 years or younger), larger (≥2 cm) solid tumors, high maximum standardized uptake values, and presence of KRAS mutation, are risk factors for STAS and can be considered for lobectomy. Smoking status and gender are still controversial risk factors for STAS.

Select octogenarians with stage IIIa non-small cell lung cancer can benefit from trimodality therapy.

Objectives: Currently, more than 36% of patients diagnosed with lung cancer are 75 years of age or older. Management of stage IIIA cancer is variable, especially for octogenarians who might not be offered surgery because of questionable benefit. In this study we investigated the outcomes of definitive chemoradiotherapy (CR) and trimodality therapy (TM) management (CR and surgery) for clinical stage IIIA non-small cell lung cancer (NSCLC) in patients 80 years of age or older. Methods: The National Cancer Data Base was queried for stage IIIA NSCLC in patients 80 years of age or older between 2004 and 2015. Patients were divided according to treatment type: definitive CR and TM. Patient demographic characteristics, facility type, Charlson-Deyo score, final tumor pathology, and survival data were extracted. Univariate analysis was performed, followed by 3:1 propensity matching to analyze overall survival differences. Unadjusted and adjusted Kaplan-Meier survival analyses were performed. Results: From the database, 6048 CR and 190 TM octogenarians were identified. Patients in the TM group were younger (82 years old [TM] vs 83 years old [CR]; P < .0001), more likely to be treated at an academic/research institution (36% [TM] vs 26% [CR]; P = .003), had greater proportion of adenocarcinoma (52% [TM] vs 34% [CR]; P < .001), and a smaller tumor size (38 mm [TM] vs 33 mm [CR]; P = .025). After 3:1 matching, the 5-year overall survival for the TM group was 29% (95% CI, 22%-38%) versus 15% (95% CI, 11%-20%) for the CR group. Conclusions: Selected elderly patients with stage IIIa NSCLC can benefit from an aggressive TM approach.