Case presentation

A 37-year-old man with poorly controlled type 2 diabetes presented with severe right-sided pleuritic chest pain, respiratory splinting, and cough. Two weeks earlier, he had been evaluated at an urgent care for cough and was prescribed a 5-day course of azithromycin for bronchitis. He then presented to our ED reporting mild, right-sided pleuritic chest pain. Vital signs were normal, and his chest radiograph showed a trace right pleural effusion (Fig 1A). He was discharged with naproxen for pleurisy. Three days later, he returned, reporting a dramatic increase in the severity of his pleuritic chest pain and a cough that had become productive of yellow-brown sputum. He denied fever, but endorsed chills and night sweats. His medications included atorvastatin, lisinopril, metformin, and saxagliptin. His parents were from Guam, although he was born and raised in San Diego, CA. He was employed as a social worker and denied any history of cigarette smoking, alcohol, or drug use.

Objective

The aim of this study was to identify independent predictors of hospital readmission for patients undergoing lobectomy for lung cancer.

Summary background data

Hospital readmission after lobectomy is associated with increased mortality. Greater than 80% of the variability associated with readmission after surgery is at the patient level. This underscores the importance of using a data source that includes detailed clinical information.

Methods

Using the Society of Thoracic Surgeons (STS) General Thoracic Surgery Database (GTSD), we conducted a retrospective cohort study of patients undergoing elective lobectomy for lung cancer. Three separate multivariable logistic regression models were generated: the first included preoperative variables, the second added intraoperative variables, and the third added postoperative variables. The c statistic was calculated for each model.

Results

There were 39,734 patients from 277 centers. The 30-day readmission rate was 8.2% (n = 3237). In the final model, postoperative complications had the greatest effect on readmission. Pulmonary embolus {odds ratio [OR] 12.34 [95% confidence interval (CI),7.94-19.18]} and empyema, [OR 11.66 (95% CI, 7.31-18.63)] were associated with the greatest odds of readmission, followed by pleural effusion [OR 7.52 (95% CI, 6.01-9.41)], pneumothorax [OR 5.08 (95% CI, 4.16-6.20)], central neurologic event [OR 3.67 (95% CI, 2.23-6.04)], pneumonia [OR 3.13 (95% CI, 2.43-4.05)], and myocardial infarction [OR 3.16 (95% CI, 1.71-5.82)]. The c statistic for the final model was 0.736.

Conclusions

Complications are the main driver of readmission after lobectomy for lung cancer. The highest risk was related to postoperative events requiring a procedure or medical therapy necessitating inpatient care.

Oral mucosal wound healing has long been regarded as an ideal system of wound resolution. However, the intrinsic characteristics that mediate optimal healing at mucosal surfaces are poorly understood, particularly in humans. We present a unique comparative analysis between human oral and cutaneous wound healing using paired and sequential biopsies during the repair process. Using molecular profiling, we determined that wound-activated transcriptional networks are present at basal state in the oral mucosa, priming the epithelium for wound repair. We show that oral mucosal wound-related networks control epithelial cell differentiation and regulate inflammatory responses, highlighting fundamental global mechanisms of repair and inflammatory responses in humans. The paired comparative analysis allowed for the identification of differentially expressed SOX2 (sex-determining region Y-box 2) and PITX1 (paired-like homeodomain 1) transcriptional regulators in oral versus skin keratinocytes, conferring a unique identity to oral keratinocytes. We show that SOX2 and PITX1 transcriptional function has the potential to reprogram skin keratinocytes to increase cell migration and improve wound resolution in vivo. Our data provide insights into therapeutic targeting of chronic and nonhealing wounds based on greater understanding of the biology of healing in human mucosal and cutaneous environments.

Introduction

There is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population.

Methods

We conducted a retrospective study at the five University of California National Cancer Institute-designated Comprehensive Cancer Centers. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and significant adverse events. Adverse events in patients who received a tyrosine kinase inhibitor (TKI) post-ICI were also captured.

Results

A total of 246 patients were identified, 170 treated with C plus ICI and 76 treated with C alone. Driver alterations included EGFR (54.9%), KRAS (32.9%), ALK (5.3%), HER2/ERBB2 (2.9%), ROS1 (1.2%), MET (1.2%), RET (0.8%), and BRAF non-V600 (0.8%). The overall PFS and OS hazard ratios were not significant at 1.12 (95% confidence interval 0.83-1.51; p = 0.472) and 0.86 (95% confidence interval: 0.60-1.24, p = 0.429), respectively. No significant differences in PFS or OS were observed in the mutational subgroups. Grade 3 or greater adverse events were lower in the C plus ICI group. The multivariate analysis for PFS and OS revealed a performance status (Eastern Cooperative Oncology Group) score of 2, and previous TKI treatment was associated with poorer outcomes with C plus ICI.

Conclusions

Our study suggests that patients with oncogenic-driven NSCLC, primarily those with EGFR-driven tumors, treated with a TKI should not subsequently receive C plus ICI. Analysis from prospective clinical trials will provide additional information on the role of ICIs in this group of patients.