Two-center analysis of cannabis on venous thromboembolism risk after traumatic injury: A matched analysis.

BACKGROUND: Conflicting evidence exists evaluating associations between cannabis (THC) and post-traumatic DVT. METHODS: Retrospective analysis (2014-2023) of patients ≥15yrs from two Level I trauma centers with robust VTE surveillance and prophylaxis protocols. Multivariable hierarchical regression assessed the association between THC and DVT risk. THC â€‹+ â€‹patients were direct matched to other drug use categories on VTE risk markers and hospital length of stay. RESULTS: Of 7365 patients, 3719 were drug-, 575 were THC â€‹+ â€‹only, 2583 were other drug+, and 488 were TCH+/other drug+. DVT rates by exposure group did not differ. TCH â€‹+ â€‹only patients had higher GCS scores, shorter hospital length of stay, and the lowest pelvic fracture and mortality rates. A total of 458 drug-, 453 other drug+, and 232 THC+/other drug â€‹+ â€‹patients were matched to 458, 453, and 232 THC â€‹+ â€‹only patients. There were no differences in DVT event rates in any paired sub-cohort set. Additionally, iteratively adjusted paired models did not show an association between THC and DVT. CONCLUSIONS: THC does not appear to be associated with increased DVT risk in patients with strict trauma chemoprophylaxis. Toxicology testing is useful for identifying substance abuse intervention opportunities, but not for DVT risk stratification in THC â€‹+ â€‹patients.

To the point: Utility of laparoscopy for operative management of stabbing abdominal trauma.

BACKGROUND: Algorithms for managing penetrating abdominal trauma are conflicting or vague regarding the role of laparoscopy. We hypothesized that laparoscopy is underutilized among hemodynamically stable patients with abdominal stab wounds. METHODS: Trauma Quality Improvement Program data (2016-2019) were used to identify stable (SBP ≥110 and GCS ≥13) patients ≥16yrs with stab wounds and an abdominal procedure within 24hr of admission. Patients with a non-abdominal AIS ≥3 or missing outcome information were excluded. Patients were analyzed based on index procedure approach: open, therapeutic laparoscopy (LAP), or LAP-conversion to open (LCO). Center, clinical characteristics and outcomes were compared according to surgical approach and abdominal AIS using non-parametric analysis. RESULTS: 5984 patients met inclusion criteria with 7 â€‹% and 8 â€‹% receiving therapeutic LAP and LCO, respectively. The conversion rate for patients initially treated with LAP was 54 â€‹%. Compared to conversion or open, therapeutic LAP patients had better outcomes including shorter ICU and hospital stays and less infection complications, but were younger and less injured. Assessing by abdominal AIS eliminated ISS differences, meanwhile LAP patients still had shorter hospital stays. At time of admission, 45 â€‹% of open patients met criteria for initial LAP opportunity as indicated by comparable clinical presentation as therapeutic laparoscopy patients. CONCLUSIONS: In hemodynamically stable patients, laparoscopy remains infrequently utilized despite its increasing inclusion in current guidelines. Additional opportunity exists for therapeutic laparoscopy in trauma, which appears to be a viable alternative to open surgery for select injuries from abdominal stab wounds. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Lessons for the next pandemic: analysis of the timing and outcomes including post-discharge decannulation rates for tracheostomy in severe COVID-19 respiratory failure.

PURPOSE: COVID-19 patients with respiratory failure frequently require prolonged ventilatory support that would typically warrant early tracheostomy. There has been significant debate on timing, outcomes, and safety of these procedures. The purpose of this study was to determine the epidemiological, hospital, and post-discharge outcomes of this cohort, based on early (ET) versus late (LT) tracheostomy. METHODS: Retrospective review (March 2020-January 2021) in a 5-hospital system of ventilated patients who underwent tracheostomy. Demographics, hospital/ICU length of stay (LOS), procedural characteristics, APACHE II scores at ICU admission, stabilization markers, and discharge outcomes were analyzed. Long-term decannulation rates were obtained from long-term acute care facility (LTAC) data. RESULTS: A total of 97 patients underwent tracheostomy (mean 61 years, 62% male, 64% Hispanic). Despite ET being frequently performed during active COVID infection (85% vs. 64%), there were no differences in complication types or rates versus LT. APACHE II scores at ICU admission were comparable for both groups; however, > 50% of LT patients met PEEP stability at tracheostomy. ET was associated with significantly shorter ICU and hospital LOS, ventilator days, and higher decannulation rates. Of the cohort discharged to an LTAC, 59% were ultimately decannulated, 36% were discharged home, and 41% were discharged to a skilled nursing facility. CONCLUSIONS: We report the first comprehensive analysis of ET and LT that includes LTAC outcomes and stabilization markers in relation to the tracheostomy. ET was associated with improved clinical outcomes and a short LOS, specifically on days of pre-tracheostomy ventilation and in-hospital decannulation rates.

Human milk oligosaccharides promote intestinal epithelium regeneration independent of the microbiota during necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) is a severe intestinal disease primarily affecting premature infants, marked by impaired epithelial regeneration. Breastfed infants are less susceptible to NEC than formula-fed ones, and human milk oligosaccharides (HMO) found in breast milk have prebiotic properties that can protect against NEC. However, it is unclear how HMOs influence intestinal epithelium regeneration in relation to the gut microbiota. METHODS: Broad-spectrum antibiotics were administered to pregnant dams to reduce the microbiota in offspring. NEC was induced through administration of hyperosmolar formula, lipopolysaccharide, and hypoxia from postnatal days (p) 5-9. Intestinal epithelial organoids were derived from p9 mice. HMOs were isolated from human donor breast milk and then solubilized in the formula for each feed or culture media for organoids. RESULTS: HMOs did not alter the microbiota profile in the presence of a normal or reduced microbiota. In the reduced microbiota, HMO treatment decreased NEC intestinal injury, and increased proliferation and stem cell activity. Additionally, in the complete absence of the microbiota, HMOs stimulated intestinal organoid growth. CONCLUSION: This study demonstrates that HMOs promoted intestinal epithelial regeneration independent of the gut microbiota. These findings provide further insight into the various benefits HMOs may have in the protection against NEC.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin (1) and variecolactone (2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues (5-7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

A Comparative Study of Laparoscopic versus Open Management of Index Small Bowel Obstruction in Children.

INTRODUCTION: There is limited literature on the optimal approach to treat adhesive small bowel obstruction (ASBO) in children. We sought to compare rates and outcomes of laparoscopic (LAP) and open (OPEN) surgery for pediatric ASBO. METHODS: A California statewide database was used to identify children (<18 years old) with an index ASBO from 2007 to 2020. The primary outcome was the type of operative management: LAP or OPEN. Secondary outcomes were hospital characteristics, patient demographics, and postoperative complications. We excluded patients treated non-operatively. RESULTS: Our study group had 545 patients. 381 (70%) underwent OPEN and 164 (30%) LAP during the index admission. Over the study period, there was increasing use of laparoscopic surgery, with higher use in older children (p < 0.001). LAP was associated with fewer overall complications (65.2% vs. 81.6%, p < 0.001), with a decreasing trend in complications over time (p < 0.001). The LAP group had significantly lower rates of bowel resection (4.9% vs. 17.1%, p < 0.001), length of stay (LOS) (17 vs. 23 days, p < 0.001), and TPN use (12.2% vs. 29.1%, p < 0.001). Mortality rates were equivalent. Although the LAP group had lower readmission rates (22.6% vs. 37.3%, p < 0.001), the length of time between discharge and readmission was similar (171 vs. 165 days, p = 0.190). DISCUSSION: The use of laparoscopic surgery for index ASBO increased over the study period. However, it was less commonly utilized in younger children. LAP had fewer overall complications as well as shorter LOS, decreased TPN use, and fewer readmissions. The benefits and risks of each approach must be weighed. LEVEL OF EVIDENCE: III.

Modified Brain Injury Guidelines for preinjury anticoagulation in traumatic brain injury: An opportunity to reduce health care resource utilization.

INTRODUCTION: The Brain Injury Guidelines (BIG) stratify patients by traumatic brain injury (TBI) severity to provide management recommendations to reduce health care resource burden but mandates that patients on anticoagulation (AC) are allocated to the most severe tertile (BIG 3). We sought to analyze TBI patients on AC therapy using a modified BIG model to determine if this population can offer further opportunity for safe reductions in health care resource utilization. METHODS: Patients 55 years or older on AC with traumatic intracranial hemorrhage (ICH) from two centers were retrospectively stratified into BIG 1 to 3 risk groups using modified BIG criteria excluding AC as a criterion. Intracranial hemorrhage progression, neurosurgical intervention (NSI), death, and worsened discharge status were compared. RESULTS: A total of 221 patients were included, with 23%, 29%, and 48% classified as BIG 1, BIG 2, and BIG 3, respectively. The BIG 3 cohort had a higher rate of AC reversal agents administered (66%) compared with the BIG 1 (40%) and BIG 2 (54%) cohorts ( p < 0.01), as well as ICH progression discovered on repeat head computed tomography (56% vs. 38% vs. 26%, respectively; p < 0.001). No patients in the BIG 1 and 2 cohorts required NSI. No patients in BIG 1 and 3% of patients in BIG 2 died secondary to the ICH. In the BIG 3 cohort, 16% of patients required NSI and 26% died. Brain Injury Guidelines 3 patients had 15 times the odds of mortality compared with BIG 1 patients ( p < 0.01). CONCLUSION: The AC population had higher rates of ICH progression than the BIG literature, but this did not lead to more NSI or mortality in the lower tertiles of our modified BIG protocol. If the modified BIG used the original tertile management on our population, then NS consultation may have been reduced by up to 52%. These modified criteria may be a safe opportunity for further health care resource and cost savings in the TBI population. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development.

4-Octyl itaconate (4-OI) is a derivative of the Krebs cycle-derived metabolite itaconate and displays an array of antimicrobial and anti-inflammatory properties through modifying cysteine residues within protein targets. We have found that 4-OI significantly reduces the production of eosinophil-targeted chemokines in a variety of cell types, including M1 and M2 macrophages, Th2 cells, and A549 respiratory epithelial cells. Notably, the suppression of these chemokines in M1 macrophages was found to be NRF2-dependent. In addition, 4-OI can interfere with IL-5 signaling and directly affect eosinophil differentiation. In a model of eosinophilic airway inflammation in BALB/c mice, 4-OI alleviated airway resistance and reduced eosinophil recruitment to the lungs. Our findings suggest that itaconate derivatives could be promising therapeutic agents for the treatment of eosinophilic asthma.

TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.

Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions.

Primary lung carcinoma or lung cancer (LC) is classified into small-cell or non-small-cell (NSCLC) lung carcinoma. Lung squamous cell carcinoma (LSCC) is the second most common subtype of NSCLC responsible for 30% of all LCs, and its survival remains low with only 24% of patients living for five years or longer post-diagnosis primarily due to the advanced stage of tumors at the time of diagnosis. The pathogenesis of LSCC is still poorly understood and has hampered the development of effective diagnostics and therapies. This review highlights the known risk factors, genetic and epigenetic alterations, miRNA biomarkers linked to the development and diagnosis of LSCC and the lack of therapeutic strategies to target specifically LSCC. We will also discuss existing animal models of LSCC including carcinogen induced, transgenic and xenograft mouse models, and their advantages and limitations along with the chemopreventive studies and molecular studies conducted using them. The importance of developing new and improved mouse models will also be discussed that will provide further insights into the initiation and progression of LSCC, and enable the identification of new biomarkers and therapeutic targets.

Trends in Management of Index Adhesive Small Bowel Obstruction in Children.

INTRODUCTION: To examine practice patterns and surgical outcomes of nonoperative versus operative management (OPM) of children presenting with an index adhesive small bowel obstruction (ASBO). METHODS: A California statewide health discharge database was used to identify children (<18 y old) with an index ASBO from 2007 to 2020. The primary study outcome was evaluating initial management patterns (nonoperative versus OPM and early [≤3 d] versus late surgery [>3 d]) of ASBO. Secondary outcomes were hospital characteristics, patient demographics, and postoperative complications. RESULTS: Of the 2297 patients identified, 1948 (85%) underwent OPM for ASBO during the index admission. Of these, 14.7% underwent early surgery within 3 d. Teaching hospitals had higher operative intervention than nonteaching centers (87.1% versus 83.7%, P = 0.034). OPM was the highest in 0-5-year-olds compared to other ages (89% versus 82%, P < 0.001). In comparison to early surgery, late surgery was associated with longer length of stay (early 7[interquartile range 5-10], late 9[interquartile range 6-17], P < 0.001), increased infectious complications (16.4% versus 9.8%, P = 0.004), and greater use of total parenteral nutrition (28.0% versus 14.3%, P = 0.001); there was no difference in bowel resection (21% versus 18%, P = 0.102) or mortality (P = 0.423). CONCLUSIONS: Our pediatric study demonstrated a high rate of OPM for index ASBO, especially in newborns and toddlers. Although operative intervention, especially late surgery, was associated with increased length of stay, increased infectious complications, and increased total parenteral nutrition use, the rates of bowel resection and mortality did not differ by management strategy. These trends need to be further evaluated to optimize outcomes.

Children's Shyness, Frontal Brain Activity, and Anxiety in the Perioperative Context.

Although preoperative anxiety affects up to 75% of children undergoing surgery each year and is associated with many adverse outcomes, we know relatively little about individual differences in how children respond to impending surgery. We examined whether patterns of anterior brain electrical activity (i.e., a neural correlate of anxious arousal) moderated the relation between children's shyness and preoperative anxiety on the day of surgery in 70 children (36 girls, Mage = 10.4 years, SDage = 1.7, years, range 8 to 13 years) undergoing elective surgery. Shyness was assessed using self-report approximately 1 week prior to surgery during a preoperative visit (Time 1), preoperative anxiety was assessed using self-report, and regional EEG (left and right frontal and temporal sites) was assessed using a dry sensory EEG headband on the day of surgery (Time 2). We found that overall frontal EEG alpha power moderated the relation between shyness and self-reported preoperative anxiety. Shyness was related to higher levels of self-reported anxiety on the day of surgery for children with lower average overall frontal alpha EEG power (i.e., higher cortical activity) but not for children with higher average overall frontal alpha EEG power (i.e., lower cortical activity). These results suggest that the pattern of frontal brain activity might amplify some shy children's affective responses to impending surgery. Findings also extend prior results linking children's shyness, frontal brain activity, and anxiety observed in the laboratory to a real-world, ecologically salient environment.

Third-Hand Exposure to E-Cigarette Vapour Induces Pulmonary Effects in Mice.

In the last decade, e-cigarette usage has increased, with an estimated 82 million e-cigarette users globally. This is, in part, due to the common opinion that they are "healthier" than tobacco cigarettes or simply "water vapour". Third-hand e-vapour exposure is the chemical residue left behind from e-cigarette aerosols, which is of concern due to its invisible nature, especially among young children. However, there is limited information surrounding third-hand e-vapour exposure. This study aimed to investigate the pulmonary effects of sub-chronic third-hand e-vapour exposure in a murine model. BALB/c mice (4 weeks of age) were exposed to a towel containing nicotine free (0 mg) e-vapour, nicotine (18 mg) e-vapour, or no e-vapour (sham) and replaced daily for 4 weeks. At the endpoint, lung function was assessed, and bronchoalveolar lavage fluid and lungs were collected to measure inflammation and fibrosis. Mice exposed to third-hand e-vapour without nicotine had alveolar enlargement compared to sham exposed controls. Mice exposed to third-hand e-vapour with nicotine had reduced bronchial responsiveness to provocation, increased epithelial thickening in large airways, increased epithelial layers in small airways, alveolar enlargement, and increased small airway collagen deposition, compared to sham exposed controls. In conclusion, our study shows that third-hand e-vapour exposure, particularly in the presence of nicotine, negatively affects the lung health of mice and highlights the need for greater public awareness surrounding the dangers of third-hand exposure to e-cigarette vapour.

Improved outcome in penile cancer with radiologically enhanced stratification protocol for lymph node staging procedures: a study in 316 inguinal basins with a mean follow-up of 5 years.

BACKGROUND: Lymph node metastasis is the main determinant of survival in penile cancer patients. Conventionally clinical palpability is used to stratify patients to Inguinal Lymph node dissection (ILND) if clinically node positive (cN +) or Dynamic sentinel node biopsy (DSNB) if clinically node negative (cN0). Studies suggest a false negative rate (FNR) of around 10% (5-13%) for DSNB. To our knowledge there are no studies reporting harder end point of survival and outcomes of all clinically node positive (cN +) patients. We present our outcome data of all patients with penile cancer including false negative rates and survival in both DSNB and ILND groups. METHODS: One hundred fifty-eight consecutive patients (316 inguinal basins), who had lymph node surgery for penile cancer in a tertiary referral centre from Jan 2008 to 2018, were included in the study. All patients underwent ultrasound (US) ± fine needle aspiration cytology (FNAC) and then MRI/ CT, if needed, to stage their disease. We used combined clinical and radiological criteria (node size, architecture loss, irregular margins) to stratify patients to DSNB vs ILND as opposed to clinical palpability alone. RESULTS: 11.2% i.e., 27/241 inguinal basins had lymph node positive disease by DSNB. 54.9% i.e., 39/71 inguinal basins (IBs) had lymph node-positive disease by ILND. 4 inguinal basins with no tracer uptake in sentinel node scans are being monitored at patient's request and have not had any recurrences to date. With a mean follow-up of 65 months (range 24-150), the false-negative rate (FNR) for DSNB is 0%. Judicious uses of cross-sectional imaging necessitated ILND in 2 inguinal basins with non-palpable nodes and negative US with false positive rate of 6.3% (2/32) for ILND. The same cohort of DSNB patients might have had 11.1% (3/27) FNR if only palpability criteria was used. 43 (28%) patients who did require cross sectional imaging as per our criteria had a low node positive rate of 4.7% (p = 0.03). Mean cancer specific survival of all node-positive patients was 105 months. CONCLUSION: The performance of DSNB improved with enhanced radiological stratification of patients to either DSNB or ILND. We for the first time report the comprehensive outcome of all lymph node staging procedures in penile cancer.

Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification.

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated that CS results in intervertebral disc (IVD) degeneration and release of MC-restricted tetramer tryptases (TTs) in the IVDs. TTs were found to regulate the expression of methyltransferase 14 (METTL14) at the epigenetic level by inducing N6-methyladenosine (m6A) deposition in the 3' untranslated region (UTR) of the transcript that encodes dishevelled-axin (DIX) domain-containing 1 (DIXDC1). That reaction increases the mRNA stability and expression of Dixdc1. DIXDC1 functionally interacts with disrupted in schizophrenia 1 (DISC1) to accelerate the degeneration and senescence of nucleus pulposus (NP) cells by activating a canonical Wnt pathway. Our study demonstrates the association between CS, MC-derived TTs, and LBP. These findings raise the possibility that METTL14-medicated DIXDC1 m6A modification could serve as a potential therapeutic target to block the development of degeneration of the NP in LBP patients.

Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery: A Nested Case-Control Study.

Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.

Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease.

Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade.

Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.

Financial vulnerability of trauma centers: A national analysis.

OBJECTIVE: Trauma centers function as an essential safeguard in the United States health care system. However, there has been minimal study of their financial health or vulnerability. We sought to perform a nationwide analysis of trauma centers using detailed financial data and a recently developed Financial Vulnerability Score (FVS) metric. METHODS: The RAND Hospital Financial Database was used to evaluate all American College of Surgeons-verified trauma centers nationwide. The composite FVS was calculated for each center using six metrics. Financial Vulnerability Score tertiles were used to classify centers as high, medium, or low vulnerability, and hospital characteristics were analyzed and compared. Hospitals were also compared by US Census region and teaching versus nonteaching hospitals. RESULTS: A total of 311 American College of Surgeons-verified trauma centers were included in the analysis, with 100 (32%) Level I, 140 (45%) Level II, and 71 (23%) Level III. The largest share of the high FVS tier was consisted of Level III centers (62%), with the majority of Level I (40%) and Level II (42%) in the middle and low FVS tier, respectively. The most vulnerable centers had fewer beds, negative operating margins, and significantly less cash on hand. Lower FVS centers had greater asset/liability ratios, lower outpatient shares, and three times less uncompensated care. Nonteaching centers were statistically significantly more likely to have high vulnerability compared with teaching centers (46% vs. 29%). Statewide analysis showed high discrepancy among individual states. CONCLUSION: With approximately 25% of Levels I and II trauma centers at high risk for financial vulnerability, disparities in characteristics, including payer mix and outpatient status, should be targeted to reduce vulnerabilities and bolster the health care safety net. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.