Early Detection of Ventilator-associated Pneumonia From Exhaled Breath in Intensive Care Unit Patients.

OBJECTIVE: Evaluate associations between volatile organic compounds (VOCs) in heat and moisture exchange (HME) filters and the presence of ventilator-associated pneumonia (VAP). BACKGROUND: Clinical diagnostic criteria for VAP have poor interobserver reliability, and cultures are slow to result. Exhaled breath contains VOCs related to gram-negative bacterial proliferation, the most identified organisms in VAP. We hypothesized that exhaled VOCs on HME filters can predict nascent VAP in mechanically ventilated intensive care unit patients. METHODS: Gas chromatography-mass spectrometry was used to analyze 111 HME filters from 12 intubated patients who developed VAP. Identities and relative amounts of VOCs were associated with dates of clinical suspicion and culture confirmation of VAP. Matched pairs t tests were performed to compare VOC abundances in HME filters collected within 3 days pre and postclinical suspicion of VAP (pneumonia days), versus outside of these days (non-pneumonia days). A receiver operating characteristic curve was generated to determine the diagnostic potential of VOCs. RESULTS: Carbon disulfide, associated with the proliferation of certain gram-negative bacteria, was found in samples collected during pneumonia days for 11 of 12 patients. Carbon disulfide levels were significantly greater ( P = 0.0163) for filters on pneumonia days. The Area Under the Curve of the Reciever Operating Characteristic curve (AUC ROC) for carbon disulfide was 0.649 (95% CI: 0.419-0.88). CONCLUSIONS: Carbon disulfide associated with gram-negative VAP can be identified on HME filters up to 3 days before the initial clinical suspicion, and approximately a week before culture confirmation. This suggests VOC sensors may have potential as an adjunctive method for early detection of VAP.

Optimal Timing for Initiation of Thromboprophylaxis After Hepatic Angioembolization.

OBJECTIVE: To evaluate the optimal timing of thromboprophylaxis (TPX) initiation after hepatic angioembolization in trauma patients. BACKGROUND: TPX after hepatic trauma is complicated by the risk of bleeding, but the relative risk after hepatic angioembolization is unknown. METHODS: Patients who underwent hepatic angioembolization within 24 hours were retrospectively identified from the 2017 to 2019 American College of Surgeons Trauma Quality Improvement Project data sets. Cases with <24-hour length of stay and other serious injuries were excluded. Venous thromboembolism (VTE) included deep venous thrombosis and PE. Bleeding complications included hepatic surgery, additional angioembolization, or blood transfusion after TPX initiation. Differences were tested with univariate and multivariate analyses. RESULTS: Of 1550 patients, 1370 had initial angioembolization. Bleeding complications were higher in those with TPX initiation within 24 hours (20.0% vs 8.9%, P <0.001) and 48 hours (13.2% vs 8.4%, P =0.013). However, VTE was higher in those with TPX initiation after 48 hours (6.3% vs 3.3%, P =0.025). In the 180 patients with hepatic surgery before angioembolization, bleeding complications were higher in those with TPX initiation within 24 hours (72% vs 20%, P <0.001), 48 hours (50% vs 17%, P <0.001), and 72 hours (37% vs 14%, P =0.001). Moreover, deep venous thrombosis was higher in those with TPX initiation after 96 hours (14.3% vs 3.1%, P =0.023). CONCLUSIONS: This is the first study to address the timing of TPX after hepatic angioembolization in a national sample of trauma patients. For these patients, initiation of TPX at 48 to 72 hours achieves the safest balance in minimizing bleeding while reducing the risk of VTE. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Induction therapy in lung transplantation: A contemporary analysis of trends and outcomes.

OBJECTIVES: We provide a contemporary consideration of long-term outcomes and trends of induction therapy use following lung transplantation in the United States. METHODS: We reviewed the United Network for Organ Sharing registry from 2006 to 2018 for first-time, adult, lung-only transplant recipients. Long-term survival was compared between induction classes (Interleukin-2 inhibitors, monoclonal or polyclonal cell-depleting agents, and no induction therapy). A 1:1 propensity score match was performed, pairing patients who received basiliximab with similar risk recipients who did not receive induction therapy. Outcomes in matched populations were compared using Cox, Kaplan-Meier and Logistic regression modeling. MEASUREMENTS AND MAIN RESULTS: 22 025 recipients were identified; 8003 (36.34%) were treated with no induction therapy, 11 045 (50.15%) with basiliximab, 1556 (7.06%) with alemtuzumab and 1421 (6.45%) with anti-thymocyte globulin. Compared with those who received no induction, patients receiving basiliximab, alemtuzumab or anti-thymocyte globulin were found on multivariable Cox-regression analyses to have lower long-term mortality (all p < .05). Following propensity score matching of basiliximab and no induction populations, analyses demonstrated a statistically significant association between basiliximab use and long- term survival (p < .001). Basiliximab was also associated with a lower risk of acute rejection (p < .001) and renal failure (p = .002). CONCLUSION: Induction therapy for lung transplant recipients-specifically basiliximab-is associated with improved long-term survival and a lower risk of renal failure or acute rejection.

A 20-year retrospective analysis of deep venous thrombosis and pulmonary embolism among combat casualties requiring damage-control laparotomy at US military Role 2 surgical units.

BACKGROUND: Combat casualties receiving damage-control laparotomy at forward deployed, resource-constrained US military Role 2 (R2) surgical units require multiple evacuations, but the added risk of venous thromboembolism (VTE) in this population has not been defined. To fill this gap, we retrospectively analyzed 20 years of Department of Defense Trauma Registry data to define the VTE rate in this population. METHODS: Department of Defense Trauma Registry from 2002 to 2023 was queried for US military combat casualties requiring damage-control laparotomy at R2. All deaths were excluded in subsequent analysis. Rates of VTE were assessed, and subgroup analysis was performed on patients requiring massive transfusion. RESULTS: Department of Defense Trauma Registry (n = 288) patients were young (mean age, 25 years) and predominantly male (98%) with severe (mean Injury Severity Score, 26), mostly penetrating injury (76%) and high mortality. Venous thromboembolism rate was high: 15.8% (DVT, 10.3%; pulmonary embolism, 7.1%). In the massively transfused population, the VTE rate was even higher (26.7% vs. 10.2%, p < 0.001). CONCLUSION: This is the first report that combat casualties requiring damage-control laparotomy at R2 have such high VTE rates. Therefore, for military casualties, we propose screening ultrasound upon arrival to each subsequent capable echelon of care and low threshold for initiating thromboprophylaxis. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Small versus large-bore thoracostomy for traumatic hemothorax: A systematic review and meta-analysis.

BACKGROUND: Traumatic hemothorax (HTX) is common, and while it is recommended to drain it with a tube thoracostomy, there is no consensus on the optimal catheter size. We performed a systematic review to test the hypothesis that small bore tube thoracostomy (SBTT) (≤14 F) is as effective as large-bore tube thoracostomy (LBTT) (≥20F) for the treatment of HTX. METHODS: Pubmed, EMBASE, Scopus, and Cochrane review were searched from inception to November 2022 for randomized controlled trials or cohort studies that included adult trauma patients with HTX who received a tube thoracostomy. Data was extracted and Critical Appraisal Skills Program checklists were used for study appraisal. The primary outcome was failure rate, defined as incompletely drained or retained HTX requiring a second intervention. Cumulative analysis was performed with χ 2 test for dichotomous variables and an unpaired t-test for continuous variables. Meta-analysis was performed using a random effects model. RESULTS: There were 2,008 articles screened, of which nine were included in the analysis. The studies included 1,847 patients (714 SBTT and 1,233 LBTT). The mean age of patients was 46 years, 75% were male, average ISS was 20, and 81% had blunt trauma. Failure rate was not significantly different between SBTT (17.8%) and LBTT (21.5%) ( p = 0.166). Additionally, there were no significant differences between SBTT vs. LBTT in mortality (2.9% vs. 6.1%, p = 0.062) or complication rate (12.3% vs. 12.5%, p = 0.941), however SBTT had significantly higher initial drainage volumes (753 vs. 398 mL, p < 0.001) and fewer tube days (4.3 vs. 6.2, p < 0.001). There are several limitations. Some studies did not report all the outcomes of interest, and many of the studies are subject to selection bias. CONCLUSION: SBTT may be as effective as LBTT for the treatment of traumatic HTX. LEVEL OF EVIDENCE: Systematic Review/Meta-Analysis; Level IV.

Open, Video- and Robot-Assisted Thoracoscopic Lobectomy for Stage II-IIIA Non-Small Cell Lung Cancer.

BACKGROUND: This study compares the short- and long-term outcomes of open vs robotic vs video-assisted thoracoscopic surgery (VATS) lobectomy for stage II-IIIA non-small-cell lung cancer (NSCLC). METHODS: Outcomes of patients with stage II-IIIA NSCLC (excluding T4 tumors) who received open and minimally invasive surgery (MIS) lobectomy in the National Cancer Database from 2010 to 2017 were assessed using propensity score-matched analysis. RESULTS: A propensity score-matched analysis of 4652 open and 4652 MIS patients demonstrated a decreased median length of stay associated with MIS compared with open lobectomy (5 vs 6 days; P < .001). There were no significant differences in 30-day mortality, 30-day readmission, or overall survival between the open and MIS groups. A propensity score-matched analysis of 1186 VATS and 1186 robotic patients showed that compared with VATS, the robotic approach was associated with no significant differences in 30-day mortality, 30-day readmission, and overall survival. However, the robotic group had a decreased median length of stay compared with VATS (4 vs 5 days; P < .001). The conversion rate was also significantly lower for robotic compared with VATS lobectomy (8.9% vs 15.9%, P < .001). CONCLUSIONS: No significant differences were found in long-term survival between open and MIS lobectomy and between VATS and robotic lobectomy for stage II-IIIA NSCLC. However, the MIS approach was associated with a decreased length of stay compared with the open approach. The robotic approach was associated with decreased length of stay and decreased conversion rate compared with the VATS approach.

Drivers of Cost Associated With Minimally Invasive Esophagectomy.

BACKGROUND: In this era of value-based healthcare, costs must be measured alongside patient outcomes to prioritize quality improvement and inform performance-based reimbursement strategies. We sought to identify drivers of costs for patients undergoing minimally invasive esophagectomy for esophageal cancer. METHODS: Patients who underwent minimally invasive esophagectomy for esophageal cancer from December 2008 to March 2020 were included. Our institutional Society of Thoracic Surgeons database was merged with financial data to determine inpatient direct accounting costs in 2020 US dollars for total, operative (surgery and anesthesia), and postoperative (intensive care, floor, radiology, laboratory, etc) services. A supervised machine learning quantitative method, the lasso estimator with 10-fold cross-validation, was applied to identify predictors of costs. RESULTS: In the study cohort (n = 240) most had ≥cT2 pathology (82%), adenocarcinoma histology (90%), and received neoadjuvant therapy (78%). Mean length of stay was 8.00 days (SD, 4.13) with 45% inpatient morbidity rate and no deaths. The largest proportions of cost were from the operating room (30%), inpatient floor (30%), and postanesthesia care/intensive care units (20%). Preoperative predictors of operative costs were age (-5.18% per decade [95% confidence interval {CI}, -9.95 to -0.27], P = .039), body mass index ≥ 30 (+12.9% [95% CI, 0.00-27.5], P = .050), forced expiratory volume in 1 second (-3.24% per 10% forced expiratory volume in 1 second [95% CI, -5.80 to -0.61], P = .017), and year of surgery (+2.55% [95% CI, 0.97-4.15], P = .002). Predictors of postoperative costs were postoperative renal failure (+91.6% [95% CI, 9.93-233.8], P = .022), respiratory failure (+414.6% [95% CI, 158.7-923.6], P < .001), pneumonia (+136.1% [95% CI, 71.1-225.8], P < .001), and reoperation (+60.5% [95% CI, 21.5-111.9], P = .001). CONCLUSIONS: Costs associated with minimally invasive esophagectomy are driven by preoperative risk factors and postoperative outcomes. These data enable surgeons and policymakers to reduce cost variation, improve quality through standardization, and ultimately provide greater value to patients.

Cerebrospinal fluid circulating tumor cells: a novel tool to diagnose leptomeningeal metastases from epithelial tumors.

BACKGROUND: Diagnosis of leptomeningeal metastasis (LM) remains challenging due to low sensitivity of CSF cytology and infrequent unequivocal MRI findings. In a previous pilot study, we showed that rare cell capture technology (RCCT) could be used to detect circulating tumor cells (CTC) in the CSF of patients with LM from epithelial tumors. To establish the diagnostic accuracy of CSF-CTC in the diagnosis of LM, we applied this technique in a distinct, larger cohort of patients. METHODS: In this institutional review board-approved prospective study, patients with epithelial tumors and clinical suspicion of LM underwent CSF-CTC evaluation and standard MRI and CSF cytology examination. CSF-CTC enumeration was performed through an FDA-approved epithelial cell adhesion molecule-based RCCT immunomagnetic platform. LM was defined by either positive CSF cytology or imaging positive for LM. ROC analysis was utilized to define an optimal cutoff for CSF-CTC enumeration. RESULTS: Ninety-five patients were enrolled (36 breast, 31 lung, 28 others). LM was diagnosed in 30 patients (32%) based on CSF cytology (n = 12), MRI findings (n = 2), or both (n = 16). CSF-CTC were detected in 43/95 samples (median 19.3 CSF-CTC/mL, range 0.3 to 66.7). Based on ROC analysis, 1 CSF-CTC/mL provided the best threshold to diagnose LM, achieving a sensitivity of 93%, specificity of 95%, positive predictive value 90%, and negative predictive value 97%. CONCLUSIONS: We defined ≥1 CSF-CTC/mL as the optimal cutoff for diagnosis of LM. CSF-CTC enumeration through RCCT is a robust tool to diagnose LM and should be considered in the routine LM workup in solid tumor patients.

Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid.

PURPOSE: Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. MATERIALS AND METHODS: We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. RESULTS: We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. CONCLUSION: The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.