Patients Follow Different Financial Hardship Trajectories in the Year after Injury.

OBJECTIVE: To determine if distinct financial trajectories exist and if they are associated with quality-of-life outcomes. SUMMARY OF BACKGROUND DATA: Financial hardship after injury measurably impacts Health-Related Quality of Life outcomes. Financial hardship, encompassing material losses, financial worry, and poor coping mechanisms, is associated with lower quality of life and increased psychological distress. However, recovery is dynamic and financial hardship may change over time. METHODS: This is a secondary analysis of a cohort of 500 moderate-to-severe nonneurologic injured patients in which financial hardship and Health-related Quality of Life outcomes were measured at 1, 2, 4, and 12 months after injury using survey instruments (Short Form-36). Enrollment occurred at an urban, academic, Level 1 trauma center in Memphis, Tennessee during January 2009 to December 2011 and follow-up completed by December 2012. RESULTS: Four hundred seventy-four patients had sufficient data for Group- Based Trajectory Analysis. Four distinct financial hardship trajectories were identified: Financially Secure patients (8.6%) had consistently low hardship over time; Financially Devastated patients had a high degree of hardship immediately after injury and never recovered (51.6%); Financially Frail patients had increasing hardship over time (33.6%); and Financially Resilient patients started with a high degree of hardship but recovered by year end (6.2%). At 12-months, all trajectories had poor Short Form-36 physical component scores and the Financial Frail and Financially Devastated trajectories had poor mental health scores compared to US population norms. CONCLUSIONS AND RELEVANCE: The Financially Resilient trajectory demonstrates financial hardship after injury can be overcome. Further research into understanding why and how this occurs is needed.

Does umbilical contamination correlate with colorectal surgery patient outcomes?

PURPOSE: Most preoperative assessment tools to evaluate risk for postoperative complications require multiple data points to be collected and can be logistically burdensome. This study evaluated if umbilical contamination, a simple bedside assessment, correlated with surgical outcomes. METHODS: A 6-point score to measure umbilical contamination was developed and applied prospectively to patients undergoing colorectal surgery at an academic medical center. RESULTS: There were 200 patients enrolled (mean age 58.1 ± 14.8; 56% female). The mean BMI was 28.6 ± 7.4. Indications for surgery included colon cancer (24%), rectal cancer (18%), diverticulitis (13.5%), and Crohn's disease (12.5%). Umbilical contamination scores were 0 (23%, cleanest), 1 (26%), 2 (21%), 3 (24%), 4 (6%), and 5 (0%, dirtiest). Umbilical contamination did not correlate with preoperative functional status (p > 0.2). Umbilical contamination correlated with increased length of stay (rho = 0.19, p = 0.007) and postoperative complications (OR 1.3, 1.02-1.7, p = 0.04), but not readmission (p = 0.3) or discharge disposition (p > 0.2). CONCLUSION: Sterile preparation of the abdomen is an important component of proper surgical technique and umbilical contamination correlates with increased postoperative complications.

Laparoscopic colectomy in the obese, morbidly obese, and super morbidly obese: when does weight matter?

PURPOSE: Previous studies have demonstrated that obese patients (BMI >30) undergoing laparoscopic colectomy have longer operative times and increased complications when compared to non-obese cohorts. However, there is little data that specifically evaluates the outcomes of obese patients based on the degree of their obesity. The aim of this study was to evaluate the impact of increasing severity of obesity on patients undergoing laparoscopic colectomy. METHODS: A retrospective review was performed of all patients undergoing laparoscopic colectomy between 1996 and 2013. Patients were classified according to their BMI as obese (BMI 30.0-39.9), morbidly obese (BMI 40.0-49.9), and super obese (BMI >50). Main outcome measures included conversion rate, operative time, estimated blood loss, post-operative complications, and length of stay. RESULTS: There were 923 patients who met inclusion criteria. Overall, 604 (65.4%), 257 (27.9%), and 62 (6.7%) were classified as obese (O), morbidly obese (MO), and super obese (SO), respectively. Clinicopathologic characteristics were similar among the three groups. The SO group had significantly higher conversion rates (17.7 vs. 7 vs. 4.8%; P = 0.031), longer average hospital stays (7.1 days vs. 4.9 vs. 3.4; P = 0.001), higher morbidity (40.3 vs. 16.3 vs. 12.4%; P = 0.001), and longer operative times (206 min vs. 184 vs. 163; P = 0.04) compared to the MO and O groups, respectively. The anastomotic leak rate in the SO (4.8%; P = 0.027) and MO males (4.1%; P = 0.033) was significantly higher than MO females (2.2%) and all obese patients (1.8%). CONCLUSION: Increasing severity of obesity is associated with worse perioperative outcomes following laparoscopic colectomy.

A National Database Analysis Comparing the Nationwide Inpatient Sample and American College of Surgeons National Surgical Quality Improvement Program in Laparoscopic vs Open Colectomies: Inherent Variance May Impact Outcomes.

BACKGROUND: Clinical and administrative databases each have fundamental distinctions and inherent limitations that may impact results. OBJECTIVE: This study aimed to compare the American College of Surgeons National Surgical Quality Improvement Program and the Nationwide Inpatient Sample, focusing on the similarities, differences, and limitations of both data sets. DESIGN: All elective open and laparoscopic segmental colectomies from American College of Surgeons National Surgical Quality Improvement Program (2006-2013) and Nationwide Inpatient Sample (2006-2012) were reviewed. International Classification of Diseases, Ninth Revision, Clinical Modification coding identified Nationwide Inpatient Sample cases, and Current Procedural Terminology coding for American College of Surgeons National Surgical Quality Improvement Program. Common demographics and comorbidities were identified, and in-hospital outcomes were evaluated. SETTINGS: A national sample was extracted from population databases. PATIENTS: Data were derived from the Nationwide Inpatient Sample database: 188,326 cases (laparoscopic = 67,245; open = 121,081); and American College of Surgeons National Surgical Quality Improvement Program: 110,666 cases (laparoscopic = 54,191; open = 56,475). MAIN OUTCOME MEASURES: Colectomy data were used as an avenue to compare differences in patient characteristics and outcomes between these 2 data sets. RESULTS: Laparoscopic colectomy demonstrated superior outcomes compared with open; therefore, results focused on comparing a minimally invasive approach among the data sets. Because of sample size, many variables were statistically different without clinical relevance. Coding discrepancies were demonstrated in the rate of conversion from laparoscopic to open identified in the National Surgical Quality Improvement Program (3%) and Nationwide Inpatient Sample (15%) data sets. The prevalence of nonmorbid obesity and anemia from National Surgical Quality Improvement Program was more than twice that of Nationwide Inpatient Sample. Sepsis was statistically greater in National Surgical Quality Improvement Program, with urinary tract infections and acute kidney injury having a greater frequency in the Nationwide Inpatient Sample cohort. Surgical site infections were higher in National Surgical Quality Improvement Program (30-day) vs Nationwide Inpatient Sample (8.4% vs 2.6%; p < 0.01), albeit less when restricted to infections that occurred before discharge (3.3% vs 2.6%; p < 0.01). LIMITATIONS: This is a retrospective study using population-based data. CONCLUSION: This analysis of 2 large national databases regarding colectomy outcomes highlights the incidence of previously unrecognized data variability. These discrepancies can impact study results and subsequent conclusions/recommendations. These findings underscore the importance of carefully choosing and understanding the different population-based data sets before designing and when interpreting outcomes research.

PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1.

The PI3K pathway is genetically altered in excess of 70% of breast cancers, largely through PIK3CA mutation and HER2 amplification. Preclinical studies have suggested that these subsets of breast cancers are particularly sensitive to PI3K inhibitors; however, the reasons for this heightened sensitivity are mainly unknown. We investigated the signaling effects of PI3K inhibition in PIK3CA mutant and HER2 amplified breast cancers using PI3K inhibitors currently in clinical trials. Unexpectedly, we found that in PIK3CA mutant and HER2 amplified breast cancers sensitive to PI3K inhibitors, PI3K inhibition led to a rapid suppression of Rac1/p21-activated kinase (PAK)/protein kinase C-RAF (C-RAF)/ protein kinase MEK (MEK)/ERK signaling that did not involve RAS. Furthermore, PI3K inhibition led to an ERK-dependent up-regulation of the proapoptotic protein, BIM, followed by induction of apoptosis. Expression of a constitutively active form of Rac1 in these breast cancer models blocked PI3Ki-induced down-regulation of ERK phosphorylation, apoptosis, and mitigated PI3K inhibitor sensitivity in vivo. In contrast, protein kinase AKT inhibitors failed to block MEK/ERK signaling, did not up-regulate BIM, and failed to induce apoptosis. Finally, we identified phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) as the PI(3,4,5)P3-dependent guanine exchange factor for Rac1 responsible for regulation of the Rac1/C-RAF/MEK/ERK pathway in these cells. The expression level of P-Rex1 correlates with sensitivity to PI3K inhibitors in these breast cancer cell lines. Thus, PI3K inhibitors have enhanced activity in PIK3CA mutant and HER2 amplified breast cancers in which PI3K inhibition down-regulates both the AKT and Rac1/ERK pathways. In addition, P-Rex1 may serve as a biomarker to predict response to single-agent PI3K inhibitors within this subset of breast cancers.

Does delayed operation increase morbidity and mortality? An analysis of emergency general surgery procedures.

BACKGROUND: Early operation is assumed to improve outcomes after emergency general surgery (EGS) procedures; however, few data exist to inform this opinion. We aimed to (1) characterize time-to-operation patterns among EGS procedures and (2) test the association between timing and patient outcomes. We hypothesize that patients receiving later operations are at greater risk for mortality and morbidity. METHODS: We performed a retrospective cohort study of the American College of Surgeons National Surgical Quality Improvement Program data for adults aged 18 to 89 years who underwent nonelective intra-abdominal operations (appendectomy, cholecystectomy, small bowel resection, lysis of adhesions, and colectomy) from 2015 to 2020. The primary outcome was 30-day postoperative mortality. Secondary outcomes were serious morbidity and all morbidity. Admission-to-operation timing was calculated and classified as early (≤48 hours) or late (>48 hours). A multivariable logistic regression model adjusted risk estimates for age, comorbidities, frailty (Modified Frailty Index, 5-item score), and other confounders. RESULTS: Of 269,959 patients (mean age, 47.0 years; 48.0% male, 61.6% White), 88.7% underwent early operation, ranging from 70.36% (lysis of adhesions) to 98.67% (appendectomy). Unadjusted 30-day mortality was higher for late versus early operation (6.73% vs. 1.96%; p < 0.0001). After risk adjustment, late operation significantly increased risk for 30-day mortality (odds ratio [OR], 1.545; 95% confidence interval [CI], 1.451-1.644), serious morbidity (OR, 1.464; 95% CI, 1.416-1.514), and all morbidity (OR, 1.468; 95% CI, 1.417-1.520). This mortality risk persisted for all EGS procedures; risk of serious and any morbidity persisted for all procedures except cholecystectomy. CONCLUSION: Late operation significantly increased risk for 30-day mortality, serious morbidity, and all morbidity across a variety of EGS procedures. We believe that these findings will inform decisions regarding timing of EGS operations and allocation of surgical resources. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Catastrophic health expenditure in nonneurological injury due to motor vehicle crash.

BACKGROUND: Motor vehicle crashes (MVCs) are a leading cause of nonfatal injury in the United States and impose a high financial cost to the patient and the economy. For many patients, this cost may be financially devastating and contribute to worsening health outcomes after injury. We aimed to describe the population level risk of catastrophic health expenditure (CHE) and determine factors associated with risk of CHE. METHODS: We performed a retrospective review using the 2014-2017 Nationwide Inpatient Sample. The study population consisted of uninsured and privately insured adults aged 26 to 64 years who were hospitalized for nonneurologic traumatic injury due to MVCs. Our measure of financial hardship was CHE, which was defined as hospital charges ≥40% of postsubsistence income. Income estimates were derived from zip-code level data using Γ distribution modeling. RESULTS: Our sample included 189,000 patients, of which 149,705 had private insurance and 39,375 were uninsured. The median estimated income for the study cohort was $66,118 (interquartile range, $65,353-$66,884). The median cost of hospitalization was $53,467 (interquartile range, $29,854-$99,914). In addition, 91.5% of uninsured patients suffering from MVC are at risk for CHE, and 10.1% of privately insured patients are at risk for CHE. Among the insured, Black, Hispanic, and low income were associated with CHE. CONCLUSION: Nine of 10 uninsured patients are at risk for CHE after hospitalization for MVC. Despite having insurance, 10% of patients are still at risk of CHE. Black, Hispanic, and low-income communities are at highest risk of having private insurance and still experiencing CHE. This is the first population level analysis after the implementation of the Affordable Care Act that assesses the financial burden of no insurance and underinsurance. These data are important to understand the effectiveness of insurance coverage and guide hospital and policy level interventions to prevent CHE. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Disposal of Unused Postoperative Opioids: A Real-World Demonstration of Surgeon-initiated Strategies Using an Activated Charcoal Bag System.

Excessive opioid prescribing following surgery creates a reservoir of unused medications available for diversion and abuse. We conducted a cohort study examining the impact of clinic-based, surgeon-initiated strategies using an activated charcoal bag (ACB) system on disposal of unused opioids. Among patients undergoing a variety of general surgery procedures, 67% of those with unused opioids disposed of them using the ACB. Our findings demonstrate practical ways to incorporate opioid disposal into surgical practice as a complement to judicious opioid prescribing.

Adrenal cavernous hemangioma: A rare tumor that mimics adrenal cortical carcinoma.

BACKGROUND: Adrenal cavernous hemangioma is a rare tumor with only 60 cases previously reported. The aim of this study was to determine the frequency and clinical significance of adrenal cavernous hemangioma at our institution. METHODS: A retrospective review of consecutive patients undergoing adrenalectomy from 1994 to 2018 was completed to determine the frequency of cavernous hemangioma, characterize the clinical presentation, imaging and pathologic features and review the operative management and outcome. RESULTS: Of 144 consecutive patients who underwent adrenalectomy by a single surgeon, 5 (3.5%) had an adrenal cavernous hemangioma. All were incidentally discovered, nonfunctional adrenal masses varying in size from 7 to 12 cm with imaging features that were indeterminate in differentiating a benign adenoma from an adrenal cortical carcinoma. Attenuation values for the adrenal masses on noncontrast computed tomography varied from 28 to 34 Hounsfield units. All adrenal cavernous hemangiomas were large, heterogeneous, complex masses with a variable presence of calcification, hemorrhage, and necrosis. These features, along with tumor enlargement were concerning for adrenal cortical carcinoma. During the operation, there was no local invasion and all adrenal tumors were successfully removed laparoscopically without tumor rupture or bleeding. All patients had an uneventful postoperative course without complications. CONCLUSION: Adrenal cavernous hemangioma is a rare tumor that can grow to a very large size without causing symptoms, making it difficult to differentiate from adrenal cortical carcinoma clinically or radiographically. Despite its large size, adrenal cavernous hemangioma can be safely resected laparoscopically.

Evaluating surgical management and outcomes of colovaginal fistulas.

BACKGROUND: Colovaginal fistula is a rare condition associated with significant morbidity. The literature characterizing colovaginal fistula repair is sparse. We present our institution's experience treating colovaginal fistulas. METHODS: A retrospective review of all patients surgically treated for colovaginal fistula between 2005 and 2015 was performed. Patient demographics, intra-operative details, and post-operative outcomes were reviewed. RESULTS: We identified 27 patients with a mean age of 71 (±13) and BMI of 30 (±9). The most common etiology for fistula was diverticulitis (n = 24, 89%). A laparoscopic approach was initiated in 19 patients (70%) and an open approach for 8 (30%) with 8 patients converted from laparoscopy to open (42%). At a mean follow-up of 18 months (±21), there were no recurrences. CONCLUSION: We present one of the largest series of the surgical management of colovaginal fistulas. Although our conversion rate was high, we recommend a laparoscopic approach be utilized when feasible.

Is Modern Medical Management Changing Ultimate Patient Outcomes in Inflammatory Bowel Disease?

BACKGROUND: The impact of modern medical management of inflammatory bowel disease (IBD) on surgical necessity and outcomes remains unclear. We hypothesized that surgery rates have decreased while outcomes have worsened due to operating on "sicker" patients since the introduction of biologic medications. METHODS: The Nationwide Inpatient Sample and ICD-9-CM codes were used to identify inpatient admissions for Crohn's disease and ulcerative colitis. Trends in IBD nutrition, surgeries, and postoperative complications were determined. RESULTS: There were 191,743 admissions for IBD during the study period. Surgery rates were largely unchanged over the study period, ranging from 9 to 12 % of admissions in both Crohn's disease and ulcerative colitis. The rate of poor nutrition increased by 67 % in ulcerative colitis and by 83 % in Crohn's disease. Rates of postoperative anastomotic leak (10.2-13.9 %) were unchanged over the years. Postoperative infection rates decreased by 17 % in Crohn's disease (18 % in 2003 to 15 % in 2012; P < 0.001) but did not show a trend in any direction in ulcerative colitis. CONCLUSIONS: Rates of IBD surgery have remained stable while postoperative infectious complications have remained stable or decreased since the implementation of biologic therapies. We identified an increase in poor nutrition in surgical patients.

Measurement of PIP3 levels reveals an unexpected role for p110ß in early adaptive responses to p110α-specific inhibitors in luminal breast cancer.

BYL719, which selectively inhibits the alpha isoform of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110a), is currently in clinical trials for the treatment of solid tumors, especially luminal breast cancers with PIK3CA mutations and/or HER2 amplification. This study reveals that, even among these sensitive cancers, the initial efficacy of p110α inhibition is mitigated by rapid re-accumulation of the PI3K product PIP3 produced by the p110ß isoform. Importantly, the reactivation of PI3K mediated by p110ß does not invariably restore AKT phosphorylation, demonstrating the limitations of using phospho-AKT as a surrogate to measure PI3K activation. Consistently, we show that the addition of the p110ß inhibitor to BYL719 prevents the PIP3 rebound and induces greater antitumor efficacy in HER2-amplified and PIK3CA mutant cancers.

Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies.

During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.